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Down Syndrome

Overview

girl with Down Syndrome
Down syndrome (DS), also known as trisomy 21, is the most common genetic disorder causing intellectual disability and the most frequently occurring human chromosomal syndrome. Distinct features of the face, hands, and feet are common. Other congenital anomalies (e.g., heart and gastrointestinal defects) and acquired conditions (e.g., hypothyroidism, hearing impairment, and celiac disease) occur with increased frequency in children with DS.

Other Names & Coding

Down's syndrome
DS
Mosaic Down syndrome
Translocation Down syndrome
Trisomy 21
ICD-10 coding

Q90.0, Trisomy 21, nonmosaicism (meiotic nondisjunction)

Q90.1, Trisomy 21, mosaicism (mitotic nondisjunction)

Q90.2, Trisomy 21, translocation

Q90.9, Down syndrome, unspecified

Coding for Down Syndrome (icd10data.com) provides further coding details.

Prevalence

The prevalence of DS varies by age (due to the combined impact of increasing life span and selective terminations decreasing birth prevalence) and country (because of dramatic differences in availability of prenatal testing and termination and population attitudes). The probability of having a baby with DS increases as the mother’s age increases but, due to higher pregnancy rates in younger women, most children with DS are born to women under 35 years of age. Changes in childhood survival have impacted the age distribution of people with DS, with more people in their fourth, fifth, and sixth decades of life.

Incidence of Down Syndrome by Maternal Age
The graph (left) is based on the National Down Syndrome Cytogenetic Register and shows pooled prevalence (per 10,000 live births) of DS by maternal age. [Alberman: 2002] Prevalence would have been higher but for DS-related elective pregnancy terminations. [de: 2017]

The estimated prevalence of DS among live births in the United States in 2010 was 1:826. The prevalence across all ages was estimated to be 1:1,499, and the estimated prevalence adjusted for age distribution in pediatric practice was 1:884. [de: 2017] [Bocian: 1999] In 2014 in the United Kingdom, the overall prevalence was 1:1574. [Alexander: 2016]

Genetics

Most individuals with trisomy 21, the additional chromosome results from sporadic nondisjunction of chromosome 21 during meiosis (>90% are of maternal origin). A small percentage (3-4%) of DS results from an unbalanced translocation between chromosome 21 and another chromosome. About 25% of these unbalanced translocations are familial; the rest are sporadic. [Bull: 2011] An even smaller percentage results from nondisjunction during mitosis of the fertilized egg, resulting in mosacism, in which only some of the cells in the body are affected. [Bull: 2011]

Prognosis

The severity of associated congenital anomalies and degree of associated cognitive disability and social adaptability is variable. People with DS have an increased risk for certain medical conditions such as congenital heart defects, respiratory and hearing problems, Alzheimer’s disease, childhood leukemia, and thyroid conditions. Scientific advances in health care for these conditions and social advances in understanding the importance of educational and social interventions have led to substantial improvements in the likelihood of a productive life for individuals with DS. With the aid of a job coach, many adults with DS are employed in the private sector. Life expectancy for people with DS has increased dramatically in recent decades – from age 12 in 1949 to age 58 and older now. [de: 2017]

Practice Guidelines

The following guideline was reaffirmed by the American Academy of Pediatrics (AAP) in 2018. [AAP: 2018]

Bull MJ and the American Academy of Pediatrics Committee on Genetics.
Health Supervision for Children With Down Syndrome.
Pediatrics. 2011;128(2):393-406. PubMed abstract / Full Text

Roles of the Medical Home

After the diagnosis of DS, the medical home should provide acute-care treatment, well-child checks, and chronic care visits. At chronic-care visits, review progress, proactively manage problems, and provide anticipatory guidance, vaccinations, and other preventive services. The medical home is pivotal in implementing screenings, evaluations, and interventions that are based on treatment guidelines. The management of DS focuses on maximizing the child's capabilities at home and optimizing social inclusion. Treatment should start as early as possible, and the medical home, in collaboration with the family, should initiate and coordinate interdisciplinary care . Develop goals that include optimizing growth and development; provide ongoing information to families about available interventions, community resources, evolving scientific understanding of trisomy 21, and emerging treatments. The family should be central in all decision-making.

Clinical Assessment

Overview

Published guidelines for surveillance, screening, and caring for children with Down syndrome (DS) tend to focus on high prevalence issues and areas where consensus can be reached. [Bull: 2011] However, a number of issues are not well-addressed, including gastroesophageal reflux disease, constipation, frequent respiratory issues, and recognition of autism and ADHD. A comprehensive review of systems and evaluation of identified issues are key at all visits.

Pearls & Alerts for Assessment

Sleep apnea is common

Sleep apnea occurs in up to 45% of individuals with Down syndrome. The etiology may be obstructive, central, or mixed. A subset of individuals exhibits clinically significant sleep apnea without overt signs of upper airway obstruction. Children may have a normal sleep study and a few years later have significant apnea. When OSA is treated with a tonsillectomy and adenoidectomy, it improves but often does not resolve the concerns. Repeat sleep study should be performed in any situation where a child has new or persistent symptoms. See Sleep under Co-Morbid Conditions, above.

Atlanto-axial instability (AAI) may not require treatment

While 13-14% of patients with DS show evidence of atlanto-axial instability (AAI) on X-ray, only 1-2% have symptoms that require treatment. Treatment guidelines no longer recommend screening all patients with X-rays. Rather, clinical care should focus on education for families regarding early symptoms and monitoring for emergence of clinical signs of AAI as discussed under orthopedics. Careful questioning for symptoms and a neurologic exam should be part of any sports PE. Community organizations have yet to effect this change in guidelines, so some may still require X-rays.

Wheezing may not be asthma

While wheezing is common, asthma is not usually an accurate diagnosis if diagnostic criteria are accurately applied. [Watts: 2013] There should be careful consideration of other potential causes.

Screening

For the Condition

Prenatal
The 2016 American College of Obstetricians and Gynecologists (ACOG) guidelines advise offering screening and diagnostic testing options, as well as counseling about risks for aneuploidy, during every pregnancy prior to 20 weeks of gestation. Testing should result from informed patient choice; women have the right to decline genetic screening in a shared-decision making model. Maternal age and other risk factors must guide interpretation of any test results. [Committee: 2016] [Bull: 2011]
  • First trimester screening, available in weeks 10-13 of gestation, includes nuchal translucency (NT) measured by ultrasound, testing maternal blood for levels of pregnancy-associated plasma protein A levels (PAPP-A) and serum-free beta or total human chorionic gonadotropin (hCG).
    • NT measurement can help assess individual fetuses in multi-fetal pregnancies (e.g., twins), but is not considered sensitive or reliable as a single test.
  • The Triple screen, available from 15 through 22 weeks of gestation, includes maternal blood levels of hCG, unconjugated estriol, and α-fetoprotein (AFP). Used in isolation, this is the least accurate screening method.
  • The Quad screen, available from 15 through 22 weeks of gestation (ideally in weeks 16-18), incorporates assessment of maternal blood levels of hCG, unconjugated estriol, α-fetoprotein (AFP), and dimeric inhibin A levels. The "Penta" screen adds measurement of levels of hyperglycosylated hCG (also known as invasive trophoblast antigen).
  • Integrated screening, currently the most accurate approach, is a two-step process that combines NT measurement with serum measures from the triple and quad screening. "Serum integrated" utilizes the same blood screening but does not include NT. Results of integrated screening are not available until the second trimester.
  • Sequential (stepwise or contingent) screening is like integrated screening except the first trimester risk assessment is used to tailor subsequent screens and diagnostic testing. This approach enables decision-making in the first trimester.
  • Cell-free DNA testing can be used to screen for aneuploidy starting at 10 weeks; it is the only screen available for use in the third trimester. This method analyzes segments of placental DNA found in maternal blood. It can be quite effective at detecting trisomy 21 in high-risk populations (those with high pre-test probability), but false positives are increased in low-risk populations.
  • Cell-free DNA testing can be used to screen for aneuploidy starting at 10 weeks and is the only screen available in the third trimester. This method analyzes uses segments of placental DNA found in maternal blood. It can be quite effective at detecting trisomy 21 in high-risk populations (i.e., high pre-test probability), but it can have increased false positives in low-risk populations.
  • Pre-implantation genetic screening can be used in in vitro fertilization (IVF).
None of these screening tests are considered diagnostic. Mothers with positive screens should be offered diagnostic testing.

Diagnostic evaluations are more invasive because they require obtaining samples of fetal tissue for genetic testing. Rates of loss associated with these procedures are 0.1% to 0.3% when performed by experienced providers. [American: 2016] Chorionic villus sampling is done at 10-13 weeks, or amniocentesis is usually performed at 15-20 weeks but can be done later. Testing of embryonic tissue is also feasible prior to implantation during in vitro fertilization.

Of Family Members

Less than 5% of confirmed diagnoses of DS are familial and thus carry risk of recurrence. [Bull: 2011] If a child with DS is determined to have a chromosomal translocation, it is important to determine if the parents carry a balanced translocation in order to provide counseling regarding recurrence risk in future pregnancies and to determine if other family members should be tested.

For Complications

The most recent guidelines [Bull: 2011] provide recommendations for universal and symptom-based screening of newborns and children with DS for a wide range of comorbid conditions. These are compiled in the Down Syndrome Checklist (2018) (PDF Document 132 KB) for use in practice.

Newborn period
Universal screening
  • Routine newborn screening
    • Hearing screening is adequate if ABR or OAE is normal; if abnormal, the child should be referred for follow-up evaluation.
    • Thyroid screening with thyroid stimulating hormone (TSH) is adequate; if the routine screen uses only T4, a TSH should be obtained during the nursery stay.
  • Echocardiogram to evaluate for congenital heart disease (a normal fetal echo is not adequate since some heart defects can be missed, in the stable infant, the echo can be completed electively in the first weeks of life).
  • Hematologic screening: Complete blood count to assess for a leukemoid reaction, myeloproliferative disorder, and polycythemia.
  • Vision screening: Evaluate for cataracts with the red reflex exam.
Symptom-based screening
  • Consider car seat trial in infants with low birth weight, heart disease, or severe hypotonia
  • Consider a modified barium swallow study for newborns with feeding difficulties, respiratory concerns, or severe hypotonia
  • Assess for anorectal atresia/stenosis or Hirschsprung’s disease in newborns who fail to pass meconium within the first 48 hours of life.
  • If clinical concerns suggest their potential, assess for intestinal atresia, airway abnormalities, obstructive sleep apnea, and gastroesophageal reflux disease.
  • Routine screening for renal and urinary tract abnormalities, atlanto-axial instability and spinal anomalies is not recommended unless indicated by symptoms (e.g., a urinary tract infection, symptoms of urinary obstruction, persistent head tilt or torticollis).
Infancy through adolescence (refer to Down Syndrome Checklist (2018) (PDF Document 132 KB) for details and frequency of recommended screening by age). Special considerations for children with DS include:
  • Hearing loss from middle ear effusion, which is often hard to visualize, is common. Some clinicians refer to ENT for routine exams to aid in monitoring.
  • Eye examinations should include assessment of red reflex. Due to the high prevalence of problems (e.g., myopia, hyperopia, cataracts, strabismus, nystagmus), all children with DS should be examined by a pediatric ophthalmologist by 6 months of age. In-office photo screening is recommended, if available, after one year of age.
  • All children with DS should be referred to an early intervention program. Bright Futures guidelines recommend standardized developmental screen (e.g., ASQ or PEDS) at 9 months of age; this should be done for any child with DS who has not been previously identified as having delays. [Committee: 2017] As many as 20-30% of children with DS will have an autism spectrum disorder; clinicians should monitor for suggestive symptoms and refer for evaluation when indicated.
  • Radiologic imaging for atlanto-axial instability (AAI) or spinal anomalies should be performed if symptoms suggest (e.g., persistent head tilt or torticollis, lower extremity increased reflexes). All children should be managed with the potential for AAI when positioning for intubation. Parents should be taught recommended activity restrictions (e.g., do not teach tumbling, no head-first diving, no trampoline till age 6 years and then only with supervision) and clinical signs that suggest a need for evaluation (e.g., increase tone in legs, change in gait or hand function, chronic headaches or neck pain, chronic head tilt).
  • Sleep study is recommended by age 4 but should be completed sooner if there are any symptoms suggestive of obstructive or central sleep apnea.
  • Consider testing for celiac disease if there is failure to thrive, chronic diarrhea, persistent constipation, chronic bloating, or iron deficiency; it is unlikely if the child has not started foods with gluten and is uncommon prior to age one.
  • Renal/urologic studies if concerns for obstruction (e.g., posterior urethral valves) or urinary tract infection

Presentations

Current prenatal screening will identify approximately 85-90% of fetuses with DS. A European study found that roughly 90% of mothers of affected fetuses opted to terminate pregnancy. [Morris: 2009] The birth of infants with DS not previously identified is becoming less common but will continue. Clinicians may be considering DS when a newborn is noted to have atypical features, hypotonia, or a DS-associated major malformation. An infant's presentation may be subtle, leading to occasional missed diagnoses in the newborn period. These infants are likely to be recognized by the primary care clinician due to poor growth, feeding concerns, developmental delays, hypotonia, or concern for a medical condition associated with DS.

Ten percent of individuals with DS are identified after 1 week of age and more than half not until adulthood (identification rates reflect past screening approaches, and it is not clear how updated screening guidelines will impact them). Delayed diagnosis is more likely when an individual has mosaic trisomy 21, in which physical features may be subtle. Mosaic trisomy 21 has been identified in adult individuals with intellectual challenges who had no physical features of DS.

Diagnostic Criteria

While physical features may suggest a diagnosis of DS, confirmation requires chromosome analysis, which, in most individuals, will reveal an extra chromosome 21. In 4% of patients with DS, analysis will find the attachment of an extra-long arm of chromosome 21 to another chromosome (translocation DS). A very small percentage have an extra chromosome 21 in only some of their somatic cells, due to nondisjunction during mitosis of the fertilized egg (mosaic DS).

Differential Diagnosis

Other genetic syndromes that can have overlapping features include Smith-Magenis syndrome and Noonan syndrome.

Since many physical features of DS occasionally occur in typical infants, the clinician should look for a constellation of findings when considering the diagnosis. Epicanthal folds, protruding tongue, simian crease, widely-spaced first and second toes, hypotonia, and up-slanting palpebral fissures are suggestive, especially in combination; however, these features can all be found in people with normal chromosomes. These issues underscore the importance of genetic testing to confirm diagnosis.

Comorbid & Secondary Conditions

Individuals with DS are at risk for many associated conditions, discussed below by organ system.

Cardiovascular
Congenital heart defects
are found in around 50% of infants with Down syndrome. [Watts: 2013] [Bull: 2011] Early mortality is associated with the presence of a cardiac defect, particularly if combined with a gastrointestinal malformation. The most common defects include:
  • Atrioventricular septal defects, with or without other heart defects (45%)
  • Ventricular septal defects, with or without other heart defects (35%)
  • Isolated secundum atrial septal defect (8%)
  • Isolated persistent patent ductus arteriosus (7%)
  • Isolated tetralogy of Fallot (4%)
  • Other (1%)
Pulmonary hypertension may be diagnosed at birth or may develop in the child with unrecognized or untreated sleep apnea or heart defect. If untreated, over the long term, pulmonary hypertension may not be reversible in the patient with an unrepaired heart defect, Eisenmenger syndrome may evolve (in which pulmonary hypertension, reversal of flow, and cyanosis develop as a left-to-right shunt switches from right to left).

Acquired valvular dysfunction is common in adults with Down syndrome without congenital heart disease (up to 50%).
  • Mitral valve prolapse is most common
  • Tricuspid, aortic, and mitral insufficiency have also been reported
Nutrition
  • Newborns with DS are at risk for feeding problems due to a weak suck, low tone, and problems related to any organ malformations. However, many mothers who breastfeed are successful if they stick with it. [Aumonier: 1983] [Bull: 2011] Some infants will need significant support during the first few weeks of life to attain success with breast or bottle.
  • Older infants may have lingering tongue thrust, which can delay success with introduction of solids.
  • Oral aversions are also common.
  • Self-feeding skills are often delayed due to delayed fine and oral motor skills, oral aversions, and behavioral challenges.
  • Older children are at risk for excessive weight gain, which may be more due to family health behaviors than characteristic of DS. [Bertapelli: 2016]
  • Behavioral feeding concerns, celiac disease, reflux, chronic constipation, and diabetes are relatively common and result in additional need to focus on nutrition.
Respiratory
Children with DS are at increased risk for recurrent acute respiratory illness, including pneumonia, aspiration, bronchiolitis syndromes, and croup, and/or chronic lung disease. They are also at increased risk for sleep-related breathing disorders included both obstructive and central apnea. Contributing factors may include:
  • Respiratory infections, such as pneumonia and bronchiolitis, are second only to congenital heart disease as causes for hospitalizations and are associated with increased morbidity and mortality compared to other children hospitalized for the same infections.
  • Structural abnormalities - midface hypoplasia, large tongue, small subglottic area, laryngomalacia, narrow nasopharynx or choanal atresia, enlarged tonsils and adenoids, tracheobronchomalacia, esophageal atresia, and tracheal stenosis. In the lungs, abnormal pulmonary vasculature, reduced number of alveoli and enlarged alveolar ducts and alveoli may predispose these children to increased respiratory problems. Subpleural lung cysts are more commonly present, although the clinical relevance of these is unclear. " Congenital heart disease can also predispose children to respiratory problems due to the complex interdependence of these body systems. [Watts: 2013]
  • Immune deficiencies – both cellular and humoral immune differences have been described. Immunoglobin G subclasses 2 and 4 have been noted to be deficient in some children who have a normal total IgG level.
  • Gastro-esophageal reflux or dysphagia leading to aspiration
Wheezing may be common, but asthma is not a likely diagnosis. [Watts: 2013] The children with DS wheeze is not fully understood, but it is postulated to stem from congenital lung abnormalities, tracheomalacia, upper airway collapse secondary to hypotonia or congenital heart disease. [Watts: 2013]

High-altitude pulmonary edema (HAPE) can occur in children with DS. This condition can occur in those with underlying congenital heart defects, left to right shunts, and/or pulmonary hypertension, but is not limited to this subset. HAPE can be an initial sign of pulmonary hypertension. [Watts: 2013]

Sleep
Sleep apnea occurs in up to 45% of children with DS, most commonly obstructive (50-80%), although central apnea can occur. [Bull: 2011]Contributing factors may include: structural abnormalities (as mentioned under Respiratory above), tonsillar/adenoidal hyperplasia, hypotonia, obesity, and brainstem dysfunction. Symptoms can include:
  • Abnormal breathing patterns in sleep
  • Snoring
  • Abnormal sleeping positions (e.g., sitting up)
  • Fragmented sleep (sometimes without snoring)
  • Inattention
  • Daytime sleepiness
  • Difficult morning arousal (due to carbon dioxide retention)
  • Early morning headaches (due to carbon dioxide retention)
  • Nocturnal enuresis
  • Failure to thrive
  • Behavioral problems
Behavioral sleep problems, including difficulty going to sleep and staying asleep, also occur in many children with DS (as well as in kids with normal chromosomes). Providing support to parents to help them optimize sleep hygiene and manage behavioral sleep issues can be very helpful.

Gastrointestinal
The incidence of gastrointestinal anomalies in DS is higher than in the non-DS population. The most common are:
  • Intestinal atresia (12% of individuals with DS) [Bull: 2011]
  • Tracheoesophageal fistula
  • Duodenal obstruction
  • Annular pancreas
  • Imperforate anus
  • Hirschsprung disease (<1%) [Bull: 2011]
Individuals with DS are also at higher risk for: Hematologic
Transient asymptomatic blood count abnormalities, including neutrophilia, thrombocytopenia, and polycythemia, can occur in neonates with trisomy 21. Ten percent of infants with DS develop transient myeloproliferative disease (characterized by the presence of blasts on the smear) with spontaneous regression in the vast majority. [Bull: 2011] However, transient myeloproliferative disease can cause significant morbidity/mortality due to rare liver/heart failure, sepsis, DIC, and hyperviscosity, and 20-30% of children with DS and myeloproliferation develop lymphoid or myeloid leukemia (often delayed with a mean age onset of 20 months). [Dixon: 2006]

Individuals with DS are at increased risk for leukemia throughout childhood. Despite the increased incidence, the development of leukemia is still a relatively rare event (~1% of individuals with DS), and routine screening (beyond a complete blood count with differential at birth) is not recommended. However, follow-up CBCs over the subsequent 36 months is important for any child who has a leukemoid reaction or evidence of myeloproliferative disease on their newborn CBC, even if it appears to normalize in the newborn period.

Screening for iron deficiency is recommended in children with trisomy 21 yearly. Hemoglobin and RBC indices perform poorly (insensitive) due to baseline mild macrocytosis in many children with DS. Guidelines suggest checking a taking a dietary/medical history and checking a hemoglobin in all patients. If the dietary/medical history identifies any risk for iron deficiency, a marker of iron storage should be measured (e.g., reticulocyte hemoglobin, ferrite, serum transferrin). [Dixon: 2010]

Neurology
  • Microcephaly is relatively common in trisomy 21.
  • Seizures prevalence in children with DS is 1-14%. [Barca: 2014] Seizure types may include infantile spasms (West syndrome), generalized tonic-clonic seizures, partial seizures, Lennox-Gastaut, and reflex seizures. Of note, some children with DS and no clinical seizures have EEG abnormalities that may complicate interpretation.
  • New-onset of focal weakness is relatively common and has a broad differential diagnosis. Etiologies found in a review of ten cases included: infarction related to Moyamoya, vaso-occlusive disease, or venus sinus thrombosis, traumatic subdural hematoma, brain abscess, spinal cord injury (from cervical spine stenosis and/or atlanto-axial instability (AAI)), and brachial plexus injury. [Worley: 2004]
  • Dementia - By age 40, Alzheimer-type neuropathologic abnormalities are found in all patients with DS, with or without clinical dementia. [Lott: 2012] More than half of individuals older than 50 years develop Alzheimer's disease (AD). Early onset epilepsy is associated with decreased risk of Alzheimer's, whereas late onset epilepsy is associated with increased risk. [Menéndez: 2005]
  • Myelopathy may result from AAI or subluxation of the occiput on C1 due to the ligamentous laxity seen in some patients with trisomy 21.
Mental Health/Behavior
Dual diagnosis refers to the co-existence of intellectual disability and a psychiatric disorder, which affects 18-38% of individuals with DS. [Capone: 2006] Co-morbid neuropsychiatric disorders include ADHD, autism spectrum disorders, stereotypical movements, oppositional defiant and disruptive behavior disorders, anxiety, depression, obsessive-compulsive disorder, and, rarely, psychosis. A summary of behavioral disorders, their presentation and treatment can be found in the following articles: Neurobehavioral Disorders in Children, Adolescents, and Young Adults with Down Syndrome. [Dykens: 2007] [Capone: 2006] Other sections of the Medical Home Portal may be helpful, including those on Autism Spectrum Disorder, Anxiety Disorders, Depression , and Attention Deficit Hyperactivity Disorder (ADHD).

Concerns about focus, attention span, activity level and/or impulsiveness (Attention deficit disorder ) are common. In a 2017, prevalence study in Sweden, about 1/3 of children with Down syndrome met diagnostic criteria for ADHD. [Oxelgren: 2017] Of these, many also met criteria for an autism spectrum disorder. The following should be considered in the evaluation of attention problems:
  • Hearing deficits
  • Vision deficits
  • Thyroid disorders
  • Sleep problems (e.g., sleep apnea can contribute to impaired attention)
  • Impaired expressive communication
  • Education setting not appropriate for cognitive level or learning style
  • Emotional problems (e.g., depression, anxiety)
  • Auditory processing disorders
These issues are summarized in Attention Problems in Down Syndrome: Is this ADHD? (1998, yet still useful) by Dianne McBrien, MD, a developmental pediatrician at Children's Hospital of Iowa.

Autism spectrum disorder (ASD) in children with DS is more common than previously thought using earlier diagnostic criteria and may be as high as 40% in children with DS. ASD is also more common in boys than girls with DS. [Oxelgren: 2017] Many children with DS and ASD also met criteria for ADHD. Standardized autism rating scales have not been validated in individuals with DS. It is therefore recommended that existing DSM criteria be rigorously applied over multiple observations in different settings. The accuracy or utility of a co-morbid diagnosis of ASD in children with profound cognitive impairment (IQ<25) has been questioned. Regressive autism has been noted to occur in children with DS at an older age than seen in children without DS who have an autistic regression. Although confirming an ASD diagnosis may be more challenging in the setting of DS, a separate ASD diagnosis is likely to help in accessing interventions such as applied behavioral analysis.

Depression in individuals with DS was researched in a 2011 review, which found rates ranging from 0-11%. In contrast to previous thought that people with DS are at higher risk for depression, this review concluded that the rates are not all that different from the general population. Onset of depressive symptoms tends to occur in adulthood, although can occur earlier, and should be distinguished from hypothyroidism and dementia. [Walker: 2011]

Ears/Hearing
Hearing loss which may be sensorineural, conductive, or mixed in etiology, can occur at higher rates in children with DS, and children ages 3-5 with DS have a 50-70% risk of serous otitis media. [Bull: 2011] During early development, even minor hearing impairment can negatively impact language and cognitive development - by adulthood, 60-80% have hearing loss.

Sino-pulmonary disease, including recurrent/chronic sinusitis and otitis occurs at higher rates. Children with DS may also have auditory processing deficits that affect word perception, short-term auditory memory, and sequential auditory memory. The following may be helpful for families: Hearing and Vision Loss Associated with Down Syndrome (TSBVI).

Eyes/Vision
Individuals with DS are at risk for: [Bull: 2011]
  • Nystagmus
  • Strabismus
  • Cataracts, including congenital and acquired
  • Lacrimal duct obstruction
  • Refractive errors (50% of children ages 3-5) leading to amblyopia
  • Keratoconus (cone-shaped cornea)
The following may be helpful for families: Hearing and Vision Loss Associated with Down Syndrome (TSBVI). All children with DS should be followed by an ophthalmologist starting at 6 months of age.

Dental
Children and young adults with DS are at risk for: [Bull: 2011]
  • Significant delay in eruption of both primary and secondary teeth
  • Missing and/or malformed teeth (hypodontia)
  • Dental crowding and overbite
  • Periodontal disease, developing in teen years may be rapidly progressive [Bagić: 2003]
  • Halitosis
  • Cheilosis from chronic oral breathing
  • Aphthous ulcers
  • Oral candidal infections
  • Necrotizing ulcerative gingivitis
Providing preventive dental care may be difficult because:
  • Cognitive and fine motor skills may limit the child's ability to perform brushing and flossing
  • Anatomy (small mouth) and oral aversions may make it difficult for others to provide care
  • Behavioral and health issues (e.g., sleep apnea, congenital heart disease) may increase the risk of sedation in the dental setting
  • Abnormalities in the roots of the teeth may impact orthodontic planning.
A helpful handout for parents: Dental Care for the Patient with Down Syndrome.

Endocrine
Thyroid disorders, both congenital and autoimmune hypothyroidism, occur with increased frequency. Congenital hypothyroidism occurs in about 1% of children with DS. [Bull: 2011] Many children will develop euthyroid autoimmune disease, evidenced by a slightly elevated TSH, normal free T4 level and positive thyroid antibodies. Although opinions vary about if and when to treat this, most endocrinologists do not treat if the child is growing well and theTSH is less than 10-12. These children should be monitored, but it may be many years before they develop a need for medications. Younger children require more frequent monitoring given the impact of hypothyroidism on brain development.

Short stature is common. The current guidelines recommend using standard growth charts rather than DS charts however subsequently updated growth charts were published that have improved characteristics. These updated height, weight, and OFC growth charts are quite useful. However, the BMI growth charts were impacted by a high prevalence of obesity in the study population and authors recommend they not be used.

Autoimmune Disorders
The following are associated with DS:
Child with Alopecia Areata
  • Alopecia areata (photo, left): Asymptomatic non-scarring hair loss with spontaneous remissions and exacerbations, often in combination with vitiligo. Alopecia may be localized or may involve the entire scalp or body. Children with alopecia/vitiligo should be carefully evaluated (history and physical) to identify any other associated autoimmune conditions.
  • Hashimoto's thyroiditis [Unachak: 2008]
  • Diabetes mellitus [Gillespie: 2006]
  • Autoimmune hepatobiliary disease (chronic active hepatitis, primary sclerosing cholangitis)
  • Auto-immune adrenalitis
  • Pernicious anemia
  • Vitiligo
  • Juvenile idiopathic arthritis [Juj: 2009]

Many other disorders thought to be autoimmune in nature have been reported, including multiple sclerosis, demyelinating neuropathy, and systemic lupus erythematosus. Though more common in adults, these disorders have been reported in children with DS. The mechanisms for autoimmune disease in DS are poorly understood. They may occur in combination and are more common in patients with certain HLA markers. In childhood, screening is only recommended for thyroid dysfunction and those with symptoms suggestive of celiac disease. However, the clinician should monitor for signs and symptoms of all of these conditions and assess when indicated.

Orthopedics
Hypotonia, ligament laxity, and increased joint flexibility lead to orthopedic concerns. Individuals may also exhibit skeletal differences, such as a thin, weak acetabular capsule, femoral anteversion, and a deficient posterior superior acetabulum that may contribute to orthopedic problems. Orthopedic issues include:
  • Spine: Occipitocervical and cervical spine instability (atlanto-axial rotary subluxation, atlanto-occipital instability), scoliosis (7-15%), spondylolisthesis, postural lordosis
  • Hip: Up to 8% may have hip problems, including developmental dysplasia of the hip (in this population, hip problems may begin after skeletal maturity and may significantly affect functional ambulation), avascular necrosis, and slipped capital femoral epiphysis.
  • Lower leg: Genu valgum, patellar dislocation
  • Feet: Planovalgus, metatarsus primus varus, hallux valgus
  • Increased risk for low bone density and vitamin D deficiency
  • Atlanto-axial instability: While 13-14% of patients with Down syndrome show evidence of atlanto-axial instability (AAI) on x-ray, only 1-2% have symptoms that require treatment. Parents should be educated to notify their physician if their child has:
    • Neck pain
    • Persistent head tilt
    • Intermittent or progressive weakness
    • Changes in gait or loss of motor skills
    • Loss of bowel or bladder control
    • Increased or decreased muscle tone in the legs
    • Changes in sensation in the hands or feet
Dermatologic
Individuals with DS are at risk for:
  • Atopic dermatitis
  • Syringomas
  • Benign skin tumors arising from sweat glands commonly about the eyes/face
  • Norwegian scabies (crusted scabies)
  • Xerosis
  • Milia-like idiopathic calcinosis cutis
  • Skin infections, such as bacterial or fungal folliculitis
  • Elastosis perforans serpiginosa: deep red raised lesions often occurring about the neck, chest, and arms
  • Angular cheilosis
  • Vitiligo
A number of benign dermatologic differences are also described including:
  • Acrocyanosis in the newborn
  • Cutis marmorata (may be present up to several months of age in infants with DS)
  • Hyperkeratosis of palms and soles
Urologic
The following conditions have been reported in infants with DS:
  • Renal hypoplasia
  • Hydro-uretero-nephrosis
  • Uretero-vesical and uretero-pelvic junction obstruction
  • Vesico-ureteral reflux
  • Posterior urethral valves
  • Cryptorchidism
  • Testicular cancer
  • Infertility (present in most but not all males with Down syndrome)
Developmental
Children with DS are at increased risk for:
  • Delayed gross and fine motor development: Motor delays are secondary to hypotonia, ligamentous laxity, decreased muscle strength, and altered body proportions (shorter arms and legs).
  • Social-emotional developmental concerns: Delays in social-emotional development can occur especially in children with Down syndrome who also have an autism spectrum disorder
  • Sensory integration concerns: Many children are sensitive to touch, manipulation, and textures in and around their mouth and other parts of their body. Sensory issues may affect oral motor skills, the ability of the parents to care for the child (e.g., dental and facial hygiene, feeding), and the willingness/ability of the child to eat a variety of tastes and textures. Sensory integration issues may be important in expressive communication since producing communicative responses requires processing and integrating sensory input.
  • Oral motor impairments: In early development, infants may be at risk for inadequate nutrition due to poor oral motor coordination and low tone. As children mature, additional oral motor problems may include difficulty with different textures, drooling, and verbal apraxia.
  • Cognitive concerns: Varying deficits in remembering and understanding sequences
  • Executive function problems: Can present as symptoms consistent with ADHD, a common comorbid condition

History & Examination

The initial evaluation of the child with suspected DS should focus on the prenatal, medical, and developmental history, as well a complete physical and developmental evaluation as outlined below.

Follow-up visits should begin with open-ended questions about patient/family concerns and issues. Review progress since last seen and intercurrent illness or evaluations. Specific symptoms and current treatment plan for underlying conditions (e.g., cardiac, thyroid, gastrointestinal) should be reviewed.

Current & Past Medical History

Document past and present co-morbid conditions, including prior evaluative (e.g., cardiac echo, swallow study, sleep study) and surgical procedures. A full review of symptoms is helpful, given the myriad co-morbid conditions associated with DS. Of particular concern are cardiorespiratory, sleep, feeding, gastrointestinal symptoms, learning/behavior, signs or symptoms of myelopathy, and concerns regarding hearing and vision.

Family History

A 3-generation pedigree is indicated, though a family history of DS or another chromosome abnormality is unlikely. The incidence of aneuploidy in offspring increases with parental age, particularly maternal age. A family history of pregnancy loss, especially miscarriages, can suggest a familial translocation.

Pregnancy/Perinatal History

The pregnancy and perinatal history may include:
  • Abnormal prenatal ultrasounds (e.g., polyhydramnios, suggesting duodenal obstruction, or minor ultrasound findings, such as redundant nuchal skin and increased nuchal translucency)
  • Abnormal first and second trimester maternal screening (including confirmation of diagnosis by amniocentesis or chorionicvillus sampling in some patients)
  • Detection of structural defects (including the prenatal diagnosis by ultrasound of cardiovascular malformations or duodenal atresia)

Developmental & Educational Progress

The child's functional abilities are key to management. Assess the child’s method and level of expressive communication and his/her understanding of language. Many children with DS have significantly higher receptive than expressive language abilities sometimes related to verbal apraxia and sometimes related to ASD. Typical DS language milestones include:
  • Smiling by 2 months (SD 1.5-4 months)
  • Verbalizing single words by 16 months (SD 9-31 months)
  • Verbalizing early phrases by 28 months (SD 19-96 months)
Average ages for attainment of gross motor skills in DS include:
  • Rolling stomach to back by 6 months
  • Rolling back to stomach by 7 months
  • Sitting independently at 11 months
  • Belly crawl (>5 ft) by 14 months
  • Pull to stand from hands and feet by 17 months
  • Independent standing (>10 sec) by 21 months
  • Walking (15-20 ft) by 26 months
There is wide variation around these averages, and the child with ongoing medical issues (e.g., repeated illness or surgeries) may exhibit further delays. However, it is a pitfall to blame excessive delays on medical issues without carefully considering the potential for co-morbid conditions such as hearing loss or autism. Review the services the child receives through early intervention, the school district, or private therapy providers, the child's rate of progress, and parents' satisfaction with current services.
Inquire about family, teacher, therapist, and other caregiver concerns regarding development, attainment of functional goals, ADHD or ASD symptoms and/or behavioral challenges. Skills in activities of daily living, eating, and community integration should be discussed with goals set for each.

Behavior challenges are common, including sleep and feeding concerns, internalizing/externalizing behaviors, and poor social inclusion. Consider whether problem behaviors and their frequency and intensity are consistent with the child's functional abilities. The 5-year-old whose receptive language skills are at the 3-year level is likely to have temper tantrums, a relatively short attention span, some oppositional behavioral and aggression. Prolonged temper tantrums, extreme irritability, or pervasive oppositional behavior would not be expected, and additional evaluation and behavioral supports would be indicated. Determine how these behaviors affect family functioning and what supports the family has to manage them.

Maturational Progress

Pubertal development should be expected within the same age parameters as for children without DS.

Social & Family Functioning

The understanding of DS by parents, siblings, and extended family members and their adaptation to the child's special needs should be discussed. When you meet with a family whose child has just been diagnosed, asking family members if they have known someone with DS often uncovers preconceived notions about outcomes. Ask about awareness of community resources for health care funding (e.g., Medicaid and relevant waivers, caveats of private insurance, including benefit exclusions and mechanisms to advocate for appropriate funding), financial supports (e.g., SSI and role of Workforce Services), services to optimize development and function (e.g., early intervention, developmental preschool, special education, inclusion models, private therapies, augmented communication supports), respite, appropriate recreational/social outlets, and transition (e.g., vocational rehabilitation, guardianship association).

Current functional goals, intervention supports, and adaptive equipment should be reviewed to identify gaps in needed support. Ensure families have access to information on life and financial planning for their child. Include the child in these discussions at a developmentally appropriate level. Pubertal development, self-exploration, menstrual hygiene, and sexuality should be discussed as the child approaches adolescence.

At all ages, ask about safety concerns, such as taking off in parking lots (consider a DMV form for a disability parking pass), refusing to wear a seat belt (consider an adapted car seat), and wandering (consider a tracking device and safety measures to prevent opening the house doors). Discuss approaches to prevent sexual victimization (e.g., discussing at the child’s level appropriate/inappropriate touch, teaching normal sexual function if appropriate for the teens cognitive level, encouraging parents to ensure all programs the child participates in have policies on prevention, and having family members treat the teen with appropriate body space behaviors for age).

Physical Exam

General

In a child with suspected DS, the presence of minor anomalies should be documented. Because these may contribute to parents' concern about the stigma of DS, reassurance about their presence is important. Common minor anomalies include:
  • Upward-slanting eyes
  • Inner epicanthal folds
  • Small upturned nose with saddle bridge
  • A protruding tongue that develops fissures with age
  • Brushfield spots
  • Small ears
  • Short neck with redundant skin folds
  • Brachycephaly
  • Flat occiput
  • Single palmar (simian) crease
  • Wide space between first and second toes (sandal toes)
  • Clinodactyly of the fifth finger

All of these can be found in individuals without DS. The presence of multiple such anomalies raises suspicion for DS or another genetic syndrome. After chromosome results are available, the minor anomalies play little role in health care decisions.

Vital Signs

Document baseline vital signs and oxygen saturation: Since Bright Futures does not recommend BP measure for the typical healthy child untill age 3 years, office staff may need to be guided to specifically check BP at well-child checks for children with DS. This is particularly important if the child has cardiovascular issues.

Growth Parameters

Height, weight, and head circumference (OFC) should be plotted on typical growth charts. DS growth charts were published in 2015 and are helpful for height, weight, and OFC. Nutritional status should also be assessed with weight for height (under age 2 years) and BMI (over age 2 years). The authors of the DS growth charts felt they should not be used for assessment of BMI as they were impacted by a high rate of obesity in the study population, rather typical growth charts should be used to assess the appropriateness of weight for height (WHO curves) and BMI (CDC curves).

Skin

Note dry skin, cheilitis, evidence of skin infection, eczema, thickened skin on palms or soles, vitiligo and alopecia.

HEENT/Oral

Assess extra-ocular movements, ocular alignment, pupil response, and presence of nystagmus. Abnormal red reflex or corneal clouding may indicate cataract. Look for evidence of nasolacrimal duct obstruction or chronic blepharitis. Look for middle ear effusions, evidence of chronic sinus infection, or poor nasal flow suggesting adenoidal enlargement. Monitoring for persistent middle ear fluid is critical, though often very difficult without special equipment (due to often very narrow ear canals) and clinical signs of persistent effusion may be minimal. Some clinicians recommend routine referral to an ENT for optimal monitoring. Tonsillar and adenoidal hypertrophy may contribute to airway obstruction. Palpate for thyroid enlargement or nodules.

Chest

Observe for signs of airway obstruction and or chronic lung disease.

Heart

Assess for murmurs, abnormalities in the first and second heart sound, or evidence of heart failure.

Abdomen

Bloating may be seen in children with celiac disease or chronic constipation. Hepatomegaly may be seen with congestive heart failure. Due to low tone, a protuberant abdomen is common. Umbilical hernias and diastasic recti are also very common.

Genitalia

Many infants with DS have a supra pubic fat pad that buries the base of the penis. Many parents will have concerns for micropenis, but in most cases, compression of this fat pad will reveal a normal phallus. This fat pad can also create challenges with circumcision if it creates pressure on a plastibel or can lead to a circumferential adhesion of redundant penile skin around the glans after circumcision if parents are not carefully retracting any redundant tissue on a daily bases during diaper changes. Assess Tanner stage. Testicular examination during yearly physical exam is important, particularly in patients unlikely to do self-exams.

Extremities/Musculoskeletal

Monitor skeletal alignment; individuals with DS are at increased risk for scoliosis. Examine for evidence of hip abnormalities, including dysplasia, slipped capital femoral epiphysis (SCFE), dislocation, and avascular necrosis of the femoral head (AVN). Pes planus is common but rarely requires intervention. Observe gait for asymmetries, hyperextension at the knees, foot inversion or eversion. Many children have atypical gaits in part due to poor motor control and low tone; some children with DS will benefit from orthotics.

Neurologic Exam

Regular assessment of hypotonia allows for periodic discussion of developmental progress and prognosis. Children with more extreme hypotonia may experience slower gross motor progress. Monitor for seizures through clinical history. Since patients who have experienced atlanto-axial dislocation generally have had warning signs, it is important to monitor for signs or symptoms of chronic spinal cord injury. Observe for head tilt or limitations in neck range of motion that suggest AA instability. The yearly physical should include examination of reflexes, including the Babinski. A child with symptoms should have immediate evaluation.

Testing

Sensory Testing

Vision
Following a normal routine newborn examination, the AAP counsels consideration of referral to an ophthalmologist within the 6 months of life. [Bull: 2011] Follow-up with a pediatric ophthalmologist, or general ophthalmologist familiar with DS, should occur annually for 1- to 5-year-olds, every 2 years for 6- to 13-year-olds, and every 3 years for 14- to 21-year-olds.

Hearing
In addition to assessment by history at every well-child visit, AAP guidelines suggest: [Bull: 2011]
  • Test by an objective method (e.g., otoacoustic emissions, brainstem auditory evoked response) at birth.
  • Repeat assessment "by objective method" or behavioral screening plus tympanometry every 6 months until normal ear-specific hearing is confirmed (usually around age 4).
  • Attempt first behavioral audiogram by 1 year and repeat annually after normal ear-specific hearing is confirmed.
  • Objective hearing assessment should be repeated whenever there is parental concern or evidence of persistent middle ear effusions.
  • Tympanometry may be helpful in the cooperative child to detect normal motility or presence of effusions.

Laboratory Testing

AAP screening guidelines recommend: [Bull: 2011]
  • Thyroid stimulating hormone (TSH) at newborn screen, 6 months, and annually. Check additional thyroid function tests if the TSH abnormal. Some experts recommend measuring thyroxine level (free T4) or thyroid antibodies routinely along with TSH screen; however, there is no consensus among international guidelines. In the event of a mildly elevated TSH, obtain a free T4 (to determine need for treatment) and measurement of thyroid antibodies may help to identify those with evolving autoimmune thyroid disease; however, only a minority will progress to hypothyroidism, and no consensus exists on the need to treat subclinical hypothyroidism.
  • Celiac testing (e.g., celiac reflexive panel which guides testing based upon age and serum IgA level for optimal sensitivity) if any suggestive symptoms. While there is lack of expert consensus on whether to routinely screen children with DS for celiac disease, the AAP recommends screening for symptoms that may be related to celiac disease in children with DS at yearly visits and perform serologic screening if symptoms are present. Some expert groups now recommend one-time testing of HLA-DQ2 and HLA-DQ8 to help exclude those individuals who are not at risk for celiac disease. [Bull: 2011] [Pavlovic: 2017]
  • Complete blood count with differential in the newborn period to screen for myeloproliferative disorder and polycythemia. Monitoring for resolution of the myeloproliferation (and continued intermittent monitoring until 3 years of age even after resolution) with a CBC is indicated in children who have had transient myeloproliferation.
  • Hemoglobin annually. Guidelines recommend yearly monitoring of hemoglobin and historically asking about risk factors of iron deficiency. Screen with a CRP/ferritin (or reticulocyte hemoglobin) yearly if there are any risk factors for iron deficiency or if the hemoglobin is <11.

Imaging

  • An echocardiogram should be performed on every newborn with DS to rule out a cardiac defect. In children diagnosed with obstructive sleep apnea, evaluation with an echocardiogram may be indicated on an intermittent basis to assess for pulmonary hypertension. Echocardiographic screening has been recommended in the AAP treatment guidelines for ages 13-21 if "there is a history of increasing fatigue, shortness of breath, or exertional dyspnea or abnormal physical exam findings, such as a new murmur or gallop." [Bull: 2011]
  • Consider a KUB in any newborn with DS if there is concern for duodenal atresia (double bubble sign). Additional assessment with upper gastrointestinal series (upper GI) and/or barium enema should be considered to assess anatomy in infants with gastrointestinal symptoms.
  • Obtain an "unprepped" barium enema for any concern for Hirschsprung disease.
  • Neuroimaging is not routinely indicated but should be considered in a child with macrocephaly or severe microcephaly beyond that typically observed in DS, a child whose development seems atypical for DS, any child with a change in neurologic functioning or developmental regression, and a child who has abnormalities on neurologic examination that cannot be attributed to DS.
  • The AAP guidelines do not recommend universal screening of infants with DS for renal and urologic abnormalities. However, any child with DS and urinary symptoms (e.g., UTI, difficulty with voiding, unexplained enuresis) should have an evaluation of the urinary tract.
  • Although not all sports programs have caught up with this recommendation, the AAP guidelines do not recommend screening for upper cervical spine instability unless symptomatic. The normal atlas-dens interval is less than 3.5 mm in children but may normally reach 5 mm in children with DS. If signs or symptoms of atlanto-axial instability emerge, evaluation should proceed with c-spine x-rays (neutral position followed by flexion/extension only if no abnormality is seen), neuroimaging, and consultation with neurosurgeon or orthopedic surgeon with expertise

Genetic Testing

Newborns can be screened for trisomy 21 with a fluorescent in situ hybridization (FISH) test when there is clinical suspicion. If the FISH screen is positive, it should be confirmed with a complete karyotype. [Bull: 2011] In utero diagnostic testing with CVS or amniocentesis nears 100% accuracy and distinguishes among the genetic types of DS: trisomy 21, translocation, and mosaicism. If a screen or cell free DNA during gestation was abnormal but in utero diagnostic testing was not completed, a karyotype should be completed in the newborn period to confirm the diagnosis and genetic etiology.
  • Fluorescent in situ hybridization (FISH) testing usually takes 1-4 days; results are not diagnostic. [Bull: 2011]
  • A karyotype performed on lymphocytes confirms the diagnosis and genetic type. e. [Bull: 2011] Karyotypes may take 10 or more days.
  • Genetic studies should be subsequently offered to the parents only when the child has a translocation. Prenatal diagnosis in future pregnancies, either with chorionic villous sampling at 10-13 weeks or amniocentesis at 15-20 weeks, is usually offered. Preimplantation testing is also available to screen blastomeres for aneuploidy and translocations, but the cost is substantial since this process requires in vitro fertilization and ICSI (intracytoplasmic sperm injection).
  • It is critical for the clinician to understand that not all insurances will fund genetic testing and its expensive. Some insurances will not approve a karyotype if the child had a positive cell free DNA in utero or a positive FISH. This is because, if clinically the child has DS, they do not consider knowing if it is a translocation or mosaic medically necessary (it does not change treatment, recurrence risk assessment is medically indicated for the parents but not the child). In general, no testing should be sent without prior authorization. This is particularly true on the outpatient side, but insurances will sometimes deny testing sent inpatient, too.

Other Testing

Sleep Study
Obtain a sleep study by age 4 or sooner if any symptoms of sleep apnea or other non-behavioral sleep problems are noted, such as restless legs.

Modified Barium Swallow (MBSS)
Guidelines recommend evaluating for aspiration with an MBSS in any infant with suggestive symptoms, including marked hypotonia, slow feeding, choking, recurrent/persistent respiratory symptoms, or failure to thrive. This will be particularly helpful if a speech and language pathologist is present during the study to assess and make recommendations.

Electroencephalogram (EEG)
An EEG can be obtained if there are concerns for seizures.

Specialty Collaborations & Other Services

Developmental Pediatrics (see Services below for local providers)

Particularly helpful to evaluate developmental pattern/progress, evaluate for concerns such as autism, recommend services to optimize development and to evaluate older children with behavioral or learning concerns.

Pediatric Cardiology (see Services below for local providers)

Depending upon sedation needs and the policies of the echo center, obtaining the recommended echocardiogram may require referral to a pediatric cardiologist. Children with cardiac lesions need long-term follow-up.

Audiology (see Services below for local providers)

If hearing screening is not provided by the early intervention program or school, referral to audiology will be needed. Children who fail screening or for whom the parents have concerns about hearing or auditory processing should be referred to audiology. Children with hearing impairment should be followed routinely.

Pediatric Ophthalmology (see Services below for local providers)

Guidelines recommend evaluation by an ophthalmologist by 6 months of age (sooner if the red reflex or another aspect of the eye examination is abnormal) and on an ongoing schedule.

Pediatric Gastroenterology (see Services below for local providers)

May be helpful in evaluating a child with vomiting, constipation, GERD, dysphagia, poor oral intake, chronic diarrhea, or suspected celiac disease.

Pediatric Genetics (see Services below for local providers)

May be helpful in diagnosis, evaluating recurrence risk and prenatal testing options (particularly in the case of translocation-related DS), and counseling the family regarding etiology and outcomes.

Pediatric Neurology (see Services below for local providers)

May be indicated when a child has neurologic findings that are not commonly seen (e.g., tremor, nystagmus, severe hypotonia), atypical neurologic findings (e.g., spasticity, ataxia), relative microcephaly or macrocephaly, developmental delays beyond those typically seen, or any regression in development or neurologic function.

Pediatric Neurosurgery (see Services below for local providers)

If concerns about atlantoaxial instability

Pediatric Orthopedics (see Services below for local providers)

May be helpful if there is a concern about gait or, more commonly in teens, back pain

Pediatric Sleep Medicine (see Services below for local providers)

Very helpful if there are concerns about sleep apnea or poor sleep.

Treatment & Management

Overview

Since there is no treatment for the underlying genetic abnormality in Down syndrome (DS), treatment focuses on the management of comorbid conditions and optimizing outcomes related to function and societal participation.

Pearls & Alerts for Treatment & Management

Respiratory infections can cause hospitalization after NICU discharge

Respiratory infections, such as pneumonia and bronchiolitis, are second only to congenital heart disease as causes for hospitalizations and are associated with increased morbidity and mortality compared to other children hospitalized for the same infections.

Altitude and pulmonary edema

A case series of high-altitude pulmonary edema was reported that included 6 children with Down syndrome. [Durmowicz: 2001] These children travelled up to moderate altitudes (1738-3252 feet) within a short period of time (several in under 24 hours) and developed pulmonary edema. Among the 6 children reported, 4 had congenital heart defects, 3 had chronic pulmonary hypertension, and 5 had developed an intercurrent illness just prior to their travel. The author suggested that care should be taken when traveling to even moderate altitudes with children with DS. Other authors have suggested an increased risk for those with obstructive sleep apnea perhaps related to altered chemo responsiveness to hypoxia. [Richalet: 2008]

Atlanto-axial instability

New onset of focal weakness or bowel/bladder incontinence merits urgent neurosurgical consultation. More of my time is spent these days explaining why x-rays are not needed to screen, helping them know the signs to watch for (and that these are rare but important to take seriously), and encouraging them to have their child participate in sports avoiding the very few activities that guidelines suggest restricting (head first diving, trained tumbling (toddlers are going to do it and stopping them just wants to make them do it more), rugby, trampoline before 6 years of age and after that ensure supervision).

Polycythemia and sleep apnea

Increased red blood cells may be noted in the setting of chronic sleep apnea.

Psychoactive medications

Many children with neurodevelopmental disorders are sensitive to psychoactive medications. Use very low doses (e.g., half the starting dose for a neurotypical child) when starting medications, such as SSRIs, and titrate slowly to avoid activation and other side effects. Having said that, many children with DS benefit from careful management of mental health issues with medications such as stimulants for ADHD, SSRIs for depression or anxiety, and mood stabilizers for self-injury in the face of ASD.

Anticipatory well care

Safety and toilet training (often as part of the child’s IEP) are often overlooked in the fray of the child’s medical needs, but they are critical to include in the child’s preventive care discussions.

How should common problems be managed differently in children with Down Syndrome ?

Growth or Weight Gain

The most current guidance is to use a standard growth chart complemented by use of the DS growth charts published in 2015 (and not the widely distributed DS growth charts previously published).

Development (cognitive, Motor, Language, Social-Emotional)

Be aware that some but not all children with DS may also have an autism spectrum disorder (ASD). Formal evaluation for an ASD in the context of DS should be performed by a specialist. Evaluation can be helpful in accessing services specific to treatment of ASD, such as ABA therapy. See Autism Spectrum Disorder for more details.

Viral Infections

Children with DS can have significant morbidity from viral respiratory infections, particularly in the face of a heart defect, pulmonary hypertension, severe LTM, or significant sleep obstruction. Some children may qualify for Synagis to reduce the risk of RSV infection; based on age and co-morbidities, influenza vaccination should be encouraged. Many children have had recurrent croup, and proactive provision of single dose steroids can be helpful.

Bacterial Infections

Due to narrow ear canals, it can be challenging to visualize tympanic membranes in children with DS and sometimes the clinician really cannot tell but suspects given the clinical scenario (e.g., the child has had a URI for a number of days and suddenly becomes febrile and sleeping poorly). In some cases, the clinician may have to make a judgement call. Over time work with an Ear, Nose, Throat specialist (otolaryngologist) to determine if persistent effusions are present and to place tubes for recurrent middle ear infections. Children with DS do have an increased prevalence of sinusitis. Many children with DS will benefit from a Pneumovax vaccination at age 2 years based upon co-morbidities.

Prescription Medications

Many children with neurodevelopmental disorders are sensitive to psychoactive medications. Use very low doses (e.g., half the starting dose for a neurotypical child) when starting medications, such as SSRIs, and titrate slowly to avoid activation and other side effects. Review with families carefully potential side effects (e.g., agitation, insomnia) and targeted symptoms (e.g., anxiety, impulsivity, depression symptoms).

Other

Many children with DS have significant oral sensory symptoms. Consideration of this when prescribing oral medications (e.g., pill crushed vs. liquid vs. sprinkles, compounding for taste) may help with compliance.

Systems

Cardiology

Congenital heart defects are found in 44% of infants with DS. [Plaiasu: 2017] Children with DS are more likely than other children with similar congenital heart defects to develop increased pulmonary vascular resistance. Fixed pulmonary vascular obstructive disease can be seen before the first birthday and may present as an apparent paradoxical improvement in cardiac symptoms. Because of this, optimal timing of surgical repair differs from that for similar cardiac lesions in children without DS. The primary care clinician to apprise the child’s cardiologist of any development of signs or symptoms of airway obstruction or sleep apnea as these may impact the child’s cardiac management.

Children with DS and congenital heart disease should receive all routine childhood immunizations, the importance of the influenza vaccine should be discussed and Pneumovax and RSV prophylaxis may be indicated for some children Endocarditis prophylaxis prior to dental procedures will be indicated in select patients. See the Dental and Oral Health Screening page for guidelines.

Adults with DS are at increased risk of valvular dysfunction, arrhythmias, and coronary artery disease. [Lin: 2008]

Specialty Collaborations & Other Services

Pediatric Cardiology (see Services below for local providers)

Important for those with congenital heart defects and those with pulmonary hypertension. All infants should have an echocardiogram.

Pediatric Sleep Medicine (see Services below for local providers)

To identify or manage a sleep disorder or sleep disordered breathing. A sleep study can help to identify the type (obstructive, central, or mixed) and severity of suspected sleep apnea, as well as other sleep disorders such as restless leg syndrome.

Nutrition/Growth/Bone

Nutritional monitoring/intervention is critical to prevent over/undernutrition and to promote self-feeding. See Nutrition under comorbid conditions for nutritional risk factors. Suboptimal growth is characteristic and begins during gestation. Growth should be plotted and followed on the same growth charts used for children without DS as well as the growth charts for DS published in 2015. [Bull: 2011] See Down Syndrome Growth Charts (CDC).

Some children will need significant support during the first few weeks of life to attain success with nursing or bottle feeding – these may include positioning, special nipples, thickening of formula, special feeding techniques (e.g., chin or jaw support), more frequent feeding, higher calorie formulas, or supplemental tube feedings. A speech therapist or occupational therapist can assess the child's suck and make recommendations regarding feeding technique. A low threshold should be maintained for a video/modified barium swallow to assess safety and optimal thickness of liquids.

Feeding therapy may also be important in the second half of infancy if a child has difficulty accepting new tastes or textures. Some children who have not had aspiration issues can develop concerns so even if a swallow study has been performed previously, a low threshold should be maintained to repeat if there are concerns suggestive of aspiration. Some children with DS appear to have limited satiety cues, and the family may need to structure portions to prevent excessive eating. A referral for behavioral support may be important to help a family implement a healthy diet, a structured feeding plan (e.g., the child refuses to eat at meal times and grazes all day), dietary changes for excessive weight gain or has food seeking behaviors. Consider prescribing a standard multivitamin to ensure adequate vitamin and mineral intake.

Consider testing for thyroid dysfunction and celiac disease in children with inadequate linear growth. However, feeding behavior and dysphagia concerns are certainly frequent causes of failure to thrive than thyroid or celiac disease. Growth hormone markers should be checked if the growth pattern is suggestive of growth hormone deficiency (e.g., failed linear growth despite good nutritional reserves).

Specialty Collaborations & Other Services

Pediatric Gastroenterology (see Services below for local providers)

Helpful for persistent vomiting, constipation, GERD, dysphagia, poor oral intake, chronic diarrhea, or suspected celiac disease.

Nutrition Assessment Services (see Services below for local providers)

Helpful in assessing nutritional status and adequacy of caloric intake, recommending special formulas and/or nutritional supplements, determining safety of nutritional supplements used for complementary therapy, and may guide the treatment of obesity.

Speech - Language Pathologists (see Services below for local providers)

May provide evaluation and intervention to optimize communication (verbal or using augmentative approaches) and cognitive abilities. In some communities, they take the role of feeding therapists. In some cases, the speech and language pathologist who is evaluating the child through early intervention can evaluate the child's feeding skills.

Occupational Therapy, Pediatric (see Services below for local providers)

Can provide intervention focused on feeding, as well as the treatment of the oral sensory issues that may affect feeding, dietary choices, behavior, and function. In some cases, the occupational therapist who is evaluating the child through early intervention can evaluate the child's feeding skills.

Respiratory

Children with DS are predisposed to pulmonary conditions that can lead to recurrent acute illness and/or chronic lung disease. For more detail, see the Respiratory section under Comorbid Conditions in Down Syndrome , Initial Diagnosis above. Strongly consider administration of the polysaccharide pneumonia vaccine (23-valent), as early as age 2, and encourage annual influenza vaccination. RSV prophylaxis may be indicated in some patients. [Watts: 2013]

Management of chronic lung disease is similar to that in patients without Down syndrome. The Portal's Asthma provides helpful information on the diagnosis and treatment of asthma/chronic airway inflammation; however, wheezing in DS often does not stem from asthma (although children with DS can have asthma like any other child!) and therefore its some cases will be less responsive to bronchodilators and controllers. Involvement of a pulmonary specialist can be helpful to manage decisions regarding the use of these.

Consider an immunology evaluation and/or evaluation for gastro-esophageal reflux and/or oral aspiration in children with repeated pneumonias, other pyogenic lung infections, or chronic lung disease.

High altitude pulmonary edema can occur in children with Down syndrome. Care should be taken when traveling to moderate altitudes, particularly for those with cardiac defects, pulmonary hypertension, or obstructive sleep apnea that might contribute to altered chemoresponsiveness to hypoxia. [Watts: 2013] If parents note symptoms, they should retreat to a lower threshold and seek care emergently if symptoms persist. If the symptoms resolve, they should discuss with their clinicians a plan to manage future travel to higher elevations.

Specialty Collaborations & Other Services

Pediatric Cardiology (see Services below for local providers)

Important for children with congenital heart defects and those with pulmonary hypertension.

Pediatric Pulmonology (see Services below for local providers)

May be helpful for children with recurrent or persistent pulmonary symptoms, chronic lung disease, chronic respiratory symptoms, recurrent pneumonia, or acute compromise in breathing/air exchange.

Sleep

Sleep apnea occurs in 30-60% of children with DS and may be asymptomatic. [Farhood: 2017] See the Comorbid Condition section in Down Syndrome , Initial Diagnosis, above, for a discussion of the factors contributing to sleep apnea and suggestive symptoms. Evaluation should include a sleep study (note: nap studies may be significantly less sensitive than overnight studies). although insurance funding issues and children’s sensory and anxiety based behavioral issues can sometimes impact the reality of getting a sleep study. The following may also be indicated:
  • Echocardiography: If a sleep study is positive for obstructive sleep apnea, an echo helps to evaluate for pulmonary hypertension. Over time a child may need a repeat echo if the OSA persists, particularly if treatment is ineffective or adherence is poor.
  • Chest radiography may be considered if there is cancer for comorbid chronic lung disease
  • Hemoglobin: Chronic hypoxia due to OSA may result in polycythemia
  • Serum bicarbonate and/or early morning blood gas will help determine the extent of carbon dioxide retention. This can be ordered as part of the sleep study if there is clinical concern for hypoventilation.
  • Evaluation by a pulmonologist boarded in sleep medicine and by an ENT specialist should be considered for all children with OSA to develop an optimal treatment plan
  • Consider evaluation for gastro-esophageal reflux if there are suggestive symptoms
Interventions may include:
  • Adenoidectomy and tonsillectomy are often successful in improving symptoms, although often symptoms do not completely resolve and may require additional interventions such as CPAP.
    • Post-operative apnea is a frequent complication, suggesting a need for longer postoperative monitoring. [Farhood: 2017] [Nation: 2017]
    • A follow-up sleep study should be considered approximately 6-8 weeks after surgery
    • A sleep endoscopy may be performed in some patients to determine anatomic contributors to obstruction, particularly if tonsils and adenoids do not appear to be the problem clinically.
  • Treatment for chronic sinusitis, allergies, or GERD may be helpful in the child with suggestive symptoms. [Brouillette: 2001]
  • The use of nighttime oxygen and/or continuous positive airway pressure (CPAP) may be recommended. Some patients are treated with high flow nasal cannula oxygen although the role of HFNC vs. CPAP is yet to be clarified. Patients often do not tolerate these devices due to oral hypersensitivity so a behavioral desensitization program may be necessary. Parents need extensive support as they face many challenges (sometimes insurmountable) in providing these treatments, are often frustrated, and are often extensively sleep deprived.
  • A plan for lifestyle intervention should be discussed with the family If obesity is contributing to OSA
  • Other surgical procedures may be indicated when the above have failed (e.g., uvulopalatoplasty, tongue reduction surgery, tracheostomy)

Specialty Collaborations & Other Services

Pediatric Sleep Medicine (see Services below for local providers)

Helpful in diagnosing and managing a sleep disorder or sleep disordered breathing. A sleep study can help identify sleep apnea and its cause, as well as other sleep disorders such as restless leg syndrome.

Pediatric Otolaryngology (see Services below for local providers)

Indicated in almost all children with documented or suspected obstructive sleep apnea to determine the contributors such as enlarged tonsils, adenoids, laryngomalacia.

Pediatric Cardiology (see Services below for local providers)

Consider referral for children with significant sleep apnea and concern for pulmonary hypertension.

Hematology/Oncology

Obtain a CBC in the newborn to screen for transient myeloproliferative disorder and polycythemia. Subsequently monitor hemoglobin annually, with testing for iron deficiency anemia when there are concerns (e.g., with a ferritin and CRP, or other iron indices). Routine monitoring for leukemia is not advised despite the increased lifetime risk as it is still very rare and presents symptomatically. If the infant had myeloproliferative disorder, monitor the complete blood count for several years after resolution. [Bull: 2011]

Gastro-Intestinal & Bowel Function

GI anomalies occur with increased frequency in DS– see the Down Syndrome , Ongoing Assessment Comorbid Conditions section for detail.
  • In the newborn period, significant vomiting or failure to pass meconium warrant immediate evaluation. The infant with significant chronic constipation should be evaluated for Hirschsprung's disease; the incidence is 25-fold higher in DS, and there is high mortality associated with enterocolitis, particularly in those patients with cardiac malformations. [Ieiri: 2009]
  • The prevalence of celiac disease in individuals with Down syndrome is about 4-10% among US Caucasians (compared to 1:150-300 in the general population). About 1/3 of individuals with Down syndrome and celiac disease have no overt clinical symptoms. [Pavlovic: 2017] Treatment includes life-long dietary exclusion of wheat, rye, barley, and possibly oats; identification and treatment of complications (e.g., anemia, malnutrition); and possibly evaluation of family members. See the Medical Home Portal's Celiac Disease for management details.
  • Functional gastrointestinal disorders such as esophageal dysmotility and chronic constipation can be a problem in children with Down syndrome and can lead to pain and decreased appetite as well as behavioral problems. [Moore: 2008] See Constipation and Gastroesophageal Reflux Disease for more detailed management information.

Specialty Collaborations & Other Services

Pediatric Gastroenterology (see Services below for local providers)

May assist in the evaluation/management of vomiting, constipation, GERD, dysphagia, poor oral intake, chronic diarrhea, or suspected celiac disease.

Neurology

See Comorbid Conditions section on neurologic conditions (microcephaly, seizures, myelopathy). In addition, special consideration should be given to the following two presentations:
  1. New onset of weakness has a broad differential diagnosis, is likely serious, and deserves prompt evaluation. [Worley: 2004] Urgent neurology consultation is indicated for new onset of focal weakness. Due to atlanto-axial instability, clinicians need to remain vigilant for signs of spinal cord injury and myelopathy and teach families what to watch for set focal weakness. All families should be educated on the signs and symptoms of myelopathy (change in gait or use of arms or hands, change in bowel or bladder function, neck pain, stiff neck, head tilt, torticollis, how the child positions his or her head, change in general function, or weakness), how to avoid high-risk activities like trampoline, football, soccer, specific gymnastics, and head first diving, and to seek care if signs/symptoms emerge. valuation should proceed with c-spine x-rays (neutral position followed by flexion/extension only if no abnormality is seen), neuroimaging, and consultation with neurosurgeon or orthopedic surgeon with expertise in this area. Families should also know about positioning precautions during anesthesia/sedation, surgical procedures, and radiographic examinations.
  2. Regression in function: : Alzheimer-type dementia is not seen in pediatric or young adult patients with DS. However, a small number of teens will present with sudden decline in function. The patients should have a complete evaluation to exclude the issues listed below. Although rare, autoimmune encephalitis has been reported in teens with DS and sudden loss of cognitive function and should also be excluded if clinically suspected based on presentation. A few patients will have no explanation and be diagnosis with DS Disintegration Disorder and, in case series, only a subset have regained prior functional level. [Worley: 2015]
    • Hearing problems
    • Visual deficits
    • Thyroid disorders
    • Sleep problems (e.g., sleep apnea can contribute to impaired attention)
    • Impaired expressive communication
    • Education or occupational setting not appropriate for cognitive level or learning style
    • Emotional problems (e.g., depression, anxiety)
    • Auditory processing disorders
    • Boredom due to lack of recreation or social outlets
    • Traumatic injury (e.g., subdural hematoma)
    • Stroke (e.g., from Moyamoya)
    • Myelopathy from atlanto-axial instability

Specialty Collaborations & Other Services

Pediatric Neurology (see Services below for local providers)

Helpful in evaluating and managing concerning neurologic findings.

Psychiatrist, Child-18 (MD) (see Services below for local providers)

May be helpful, particularly in the evaluation of cognitive decline to exclude mental health concerns (e.g., depression) as a contributing factor.

Developmental Pediatrics (see Services below for local providers)

May be helpful in evaluating unusual developmental patterns (e.g., associated autism) or cognitive decline.

Mental Health/Behavior

See Down Syndrome , Initial Diagnosis, Comorbid Conditions section for details about dual diagnosis and evaluation.

Behavioral supports and parent training remain the best management for behavioral challenges. However, carefully target use of psychotropic medication can be beneficial. Little research has been published to guide use medications for ADHD, depression, anxiety, and cognitive function in children with DS. In general, individuals with neurodevelopmental disabilities may have idiosyncratic reactions to psychotropic medications. A patient may show a positive response at a relatively low dose or may experience significant adverse effects at a minimal dose. Initiating treatment at a low dose (e.g., half of the starting dose for a neurotypical child) and gradual upward titration may help identify the appropriate dose for a patient while minimizing the potential for adverse effects. Recognize the lack of evidence upon which to base treatment, cautiously define for the family the goals of the medication to be observed (e.g., focus in the case of ADHD), be cautiously watch for side effects. Families need to understand the specific goal of the medication (i.e., the treatment target) as opposed to expecting a broad impact on their child’s behavior.

The most commonly prescribed types of psychoactive medication for children with DS in the United States include stimulants, selective serotonin reuptake inhibitors, atypical antipsychotics, and alpha-adrenergic agonists. [Downes: 2015] A 2016 study of guanfacine used to treat symptoms of ADHD in children with Down syndrome showed a positive impact on irritability and hyperactivity, and the medication was generally well-tolerated. [Capone: 2016]

There has been limited study regarding interventions for autism spectrum disorders in DS. A small trial of risperidone in children with DS, autism, severe intellectual disability, and disruptive behaviors and self- injury demonstrated the potential for benefit but cautioned that side-effects (weight gain, metabolic alterations) might limit long-term utility. [Capone: 2008] See Autism Spectrum Disorder, Treatment & Management for a discussion of behavioral and educational interventions and medications used in the approach to autism.

A 2017 review of pharmaceutical trials aimed at treating cognitive and adaptive function impairments in individuals with DS revealed many more questions than answer; current definitive guidance is lacking. [Keeling: 2017]

Specialty Collaborations & Other Services

Psychologist, Child-18 (PhD, PsyD) (see Services below for local providers)

Can provide standardized testing to help to understand a child's neurocognitive profile (e.g., intelligence testing and autism-specific testing), provide behavioral guidance, and counseling/therapy. A psychologist with experience working with patients with dual diagnosis will be critical.

Developmental Assessment (see Services below for local providers)

Often includes developmental pediatricians, neurologists, psychologists, speech and language pathologists, and occupational therapists; can document current functional abilities and make recommendations for intervention programming.

Psychiatrist, Child-18 (MD) (see Services below for local providers)

Particularly helpful for patients with dual diagnosis.

Developmental - Behavioral Pediatrics (see Services below for local providers)

Can provide support in ensuring optimal health monitoring, identification of co-morbid conditions, assessing developmental progress and assuring optimal intervention services, and management of behavioral concerns.

Ears/Hearing

By adulthood, 60-80% of individuals with DS have hearing loss due to sensorineural, conductive, or combined causes. During early development, even minor hearing loss can negatively impact the development of hearing, speech, and intellect. Auditory processing deficits may exist in some children although often hard to diagnose. See Ears/Hearing section above under Co-morbid Conditions in Down Syndrome , Initial Diagnosis above, for details of hearing monitoring.

If a child is identified as having an auditory/hearing impairment, consider:
  • Full evaluation and monitoring by an audiologist for diagnosis, to determine benefit from amplification (e.g., hearing aid, FM trainer) and family support
  • If diagnosed in the newborn period, consider sending testing for CMV (in some states this may be mandated by law)
  • All children should be evaluated by an otolaryngologist. If the hearing loss is conductive, ventilation tubes may be indicated.
  • Evaluation by a speech and language therapist for program planning and family support
  • Notification of the child's teacher so that the child’s IEP can be adapted to provide appropriate classroom modifications. The public schools hearing support services should be consulted to advise on classroom modifications such as:
    • Limiting background noise in teaching environments
    • Optimal positioning of the child in the classroom
    • Ensuring the child can always see the speaker's face
    • Slowing the pace of verbally presented material
    • Checking in with the child to verify understanding
    • Increased use of visual materials in the classroom
    • Total or alternate communication programming
    • An intervener or aid indicated
  • Local programs for the hearing impaired should be contacted to advise the child's school, teacher, and family
  • Vision should be evaluated to ensure there is no additional sensory deficit
Once a hearing impairment is identified, continued monitoring of hearing and vision are indicated to identify any changes over time. See the Hearing Loss & Deafness for more information.

Specialty Collaborations & Other Services

Audiology (see Services below for local providers)

Can provide hearing screening, monitor hearing status, evaluate for and adjust amplification, and help families identify intervention services and adaptations.

Pediatric Otolaryngology (see Services below for local providers)

Consider referral for recurrent otitis media and/or conductive hearing loss, or if unable to visualize the eardrum or monitor for effusion. May also be indicated for obstructive sleep apnea or recurrent sinus infection.

Public Special Schools (see Services below for local providers)

May offer specialized classroom settings or consultation with a classroom teacher regarding modifications to aid the child with auditory impairment. May also offer infant and parent education programs.

Eyes/Vision

Individuals with DS are at risk for a number of ocular abnormalities as outlined in the DS, Clinical Assessment Comorbid Conditions section. Monitoring vision is key to prevent secondary, preventable/treatable disability. Referral to pediatric ophthalmology is recommended by 6 months of age (sooner if eye examination is abnormal). Management of visual impairment may be complicated by the child's ability to tolerate glasses, patching, or other intervention.

Specialty Collaborations & Other Services

Pediatric Ophthalmology (see Services below for local providers)

Perform detailed vision exams, prescribe glasses and other interventions, and perform surgery when necessary.

Public Special Schools (see Services below for local providers)

May offer specialized classroom settings or consultation with a classroom teacher regarding modifications to aid the child with visual impairment. May also offer infant and parent education programs.

Dental

Children and young adults with DS are at risk for multiple oral and dental disorders, as outlined in the Down Syndrome , Initial Diagnosis, Comorbid Condition section.

To assist in the prevention and early detection of dental disorders and associated complications, the primary care provider should:
  • Encourage routine dental care. Families may need support in identifying a provider and/or advocating for funding. Dental check-ups are recommended by age 1 year and then every 6 months. If indicated, facilitate care by offering the dental care provider relevant information about DS. See Dental and Oral Health Screening for more information about how to assess and prevent dental problems in the primary care setting.
  • Provide fluoride varnish at well checks as recommended by the Bright Futures Guidelines and ensure adequate home water fluoridation or prescribe supplementation.
  • Manage children will resist brushing due to sensory issues. Children with feeding behaviors that result in grazing, frequent bottle sipping, or night time oral intake are at increased risk and ideally these behaviors should be addressed. Many children are on thickened water. Unfortunately, thickened water results in frequent carbohydrate exposure to the teeth and can result in severe caries. If improvement in dysphagia allows, discontinuation of thickened water should occur as soon as possible.
  • Ensure that families and dental care providers are aware of medical issues that may affect care (e.g., need for bacterial prophylaxis, sedation risks).
  • Monitor general oral hygiene and dental health and discuss issues with families as they arise. If signs of periodontal disease are evident, refer as soon as possible.
  • Help the child/teen/family manage halitosis, which may significantly affect social inclusion. Simple interventions, such as tongue brushing, mouthwashes, breath fresheners, and better dental hygiene may help. Medical issues that can cause halitosis include chronic sinusitis, gastro-esophageal reflux, drooling, and periodontal disease.
The Dental and Oral Health Screening page provides guidelines for bacterial endocarditis prophylaxis.

Specialty Collaborations & Other Services

General Dentistry (see Services below for local providers)

It is important that a dentist has previously worked with children with special health care needs and is equipped to provide safe sedation for procedures as necessary.

Pediatric Dentistry (see Services below for local providers)

May be more comfortable with children with developmental delays. Referral to special centers may be necessary if a child requires sedation for dental treatment, particularly if the child's medical status places them at increased risk for complications of sedation.

Orthodontics (see Services below for local providers)

Patients with missing/malformed teeth, dental crowding, malalignment, or malocclusion should be referred to an orthodontist familiar with treating these issues in patients with DS.

Occupational Therapy, Pediatric (see Services below for local providers)

For help with sensory resistance to brushing and behavioral feeding issues that predispose to caries development

Dental Care Expense Assistance (see Services below for local providers)

Funding is often a barrier to optimal dental care. Some programs offer assistance with dental funding.

Endocrine/Metabolism

Thyroid disorders, particularly congenital, autoimmune, and subclinical hypothyroidism occur with increased frequency in DS. Management of hypothyroidism does not differ from that in individuals without DS; however, there is considerable disagreement regarding treatment of subclinical hypothyroidism (when the TSH is elevated but free T4 is normal). Some endocrinologists favor “preventative” (early use of thyroxine supplementation); however, this practice is not part of the AAP guidelines. Because of this lack of consensus, the AAP recommends consultation with a Pediatric Endocrinologist. However, since sometimes this is transient, in the otherwise healthy thriving child with a mild election of TSH (e.g., <12) and normal free t4, repeating the labs in 6-8 weeks before referring may reduce excessive referrals. Growth is discussed above under Nutrition/Growth/Bone.

Specialty Collaborations & Other Services

Pediatric Endocrinology (see Services below for local providers)

May be helpful in diagnosis and management of thyroid dysfunction or other hormonal disorders.

Immunology/Infectious Disease

Individuals with DS are at risk for autoimmune disorders as outlined under Down Syndrome , Initial Diagnosis, Comorbid Conditions. Management of autoimmune disorders does not differ from that in individuals without DS. The DS screening guidelines only address routine screening for thyroid disorders and celiac disease. Clinicians need to stay attuned to signs and symptoms that might suggest the development of other autoimmune conditions (e.g., Addison's, type I DM).

Specialty Collaborations & Other Services

Pediatric Endocrinology (see Services below for local providers)

May be helpful in optimizing management of thyroid or other hormonal disorders, including auto-immune adrenalitis and diabetes mellitus.

Pediatric Dermatology (see Services below for local providers)

Should be knowledgeable about the latest treatments for vitiligo and alopecia areata.

Pediatric Gastroenterology (see Services below for local providers)

Can evaluate for celiac disease if blood screening tests are positive and help to diagnose and treat autoimmune hepatobiliary disease.

Pediatric Rheumatology (see Services below for local providers)

Can evaluate children with arthritic symptoms and diagnose and treat conditions such as juvenile idiopathic arthritis and lupus.

Musculoskeletal

Individuals with DS are at risk for primary anatomic skeletal differences as well as complications of hypotonia, ligament laxity, and increased joint flexibility. See Down Syndrome , Initial Diagnosis, Comorbid Conditions section for details. Regular exercise and weight control should be emphasized to reduce the risk of degenerative musculoskeletal disease. [Mik: 2008] Some authors suggest yearly monitoring by an orthopedic surgeon for prompt identification and management of musculoskeletal disorders that may limit function. [Caird: 2006]

Specialty Collaborations & Other Services

Pediatric Orthopedics (see Services below for local providers)

Can monitor the musculoskeletal exam of children at risk, evaluate and optimize gait, and provide management options for identified musculoskeletal problems.

Bone Densitometry/DEXA (see Services below for local providers)

Can be used to evaluate for osteopenia; however, children must be scanned in a facility that maintains normative pediatric data.

Pediatric Endocrinology (see Services below for local providers)

Can evaluate for the underlying causes of osteopenia or osteoporosis.

Pediatric Neurosurgery (see Services below for local providers)

Referral may be indicated if cervico-spinal instability is identified on screening X-rays or by symptoms.

Skin & Appearance

Individuals with DS are at risk for a number of dermatologic conditions. See the Down Syndrome , Initial Diagnosis Comorbid Conditions section for details of these conditions.
  • Patients with alopecia areata and/or vitiligo should be evaluated for other autoimmune conditions, including thyroid disorders and celiac disease. Therapies may be helpful (e.g., topical and intralesional steroids), though individual response varies and there is a high rate of spontaneous remission and relapse. Psychosocial support, coping mechanisms, and peer education may be important.
  • Angular cheilosis may be treated with a mild steroid cream unless fungal or bacterial super-infection is suspected.
  • Syringomas may be removed with laser treatments if indicated.
  • A dermatologic consult should be considered if atopic dermatitis, dry skin or xerosis is resistant to treatment (which is often the case).
  • · Thickened skin on palms and soles is common and benign.

Specialty Collaborations & Other Services

Pediatric Dermatology (see Services below for local providers)

Helpful in managing vitiligo, alopecia, chronic dry skin, and eczema refractory to treatment.

Pediatric Infectious Disease (see Services below for local providers)

Helpful for chronic, severe, or recurrent skin infections such as folliculitis, angular chelosis, and Norwegian scabies.

Genito-Urinary

Individuals with DS are at risk for multiple renal and collecting system abnormalities as outlined in the Down Syndrome , Initial Diagnosis, Comorbid Conditions section. Treatment of urologic conditions is based upon the malformation present and should be guided by a pediatric urologist.

Specialty Collaborations & Other Services

Pediatric Urology (see Services below for local providers)

Helpful for patients with urinary tract abnormalities or those with persistent unexplained urinary symptoms.

Maturation/Sexual/Reproductive

The clinician can provide families and children/adolescents with DS with information about these issues as well as model how to talk about these issues in understandable, accurate ways. Issues of sexuality in DS include:
  • Body parts and pubertal maturation
  • Personal care and hygiene
  • Menstrual management
  • Masturbation
  • Personal space, privacy, and social norms
  • The risks of sexual abuse
  • Dating and marriage
  • Reproduction and fertility including family planning and pregnancy outcomes
  • Sexually transmitted diseases
  • Individuals with DS as parents

The clinician should encourage the family to have open and clear discussions with their child or adolescent so he or she can learn about what is happening during puberty and understand the family’s values. The AAP’s 2006 clinical report on Sexuality of Children and Adolescents with Developmental Disabilities is an excellent resource. [Murphy: 2006] Also see Patient Education under Down Syndrome , Services & Other Resources for more resources for clinicians and families.

Specialty Collaborations & Other Services

Pediatric Urology (see Services below for local providers)

A urologist may aid in the evaluation of sexual dysfunction (e.g., impotence).

Gynecology (Ped/Adol, Special Needs) (see Services below for local providers)

A gynecologist with expertise in pediatric/adolescent issues can provide family planning guidance and, when indicated/desired, menstrual suppression management.

Development/Motor

Gross Motor Impairments
Most children with DS have delayed gross motor development secondary to hypotonia, ligamentous laxity, decreased muscle strength, motor planning challenges. Physical therapy is important for young children with DS to teach correct strengthening exercises and to prevent the child from using compensatory motor patterns that will be detrimental in the long run. Common issues in children who do not receive adequate physical therapy include:
  • Standing and walking with their hips in external rotation, knees stiff, and feet flat and turned out
  • Sitting with their trunk rounded and pelvis tilted back
  • Standing with a lordosis
Before age 3, physical therapy is usually available through an Early Intervention Program, which will focus on teaching parents to work with the child in the home. An additional benefit will be the ongoing education about their child's abilities and how best to work with him or her. For older children, a physical therapist may design an exercise program to prevent deconditioning and/or obesity. At school, physical therapy may design adapted physical education programs. See Adapted Athletic Programs (general).

Fine Motor Impairments
Fine motor impairments are common and are usually treated by working through early intervention in infancy and early childhood, then with an occupational therapist to improve skills and develop adaptive techniques.

Sensory Integration Concerns
Many children with DS are sensitive to touch, manipulation, and textures in and around their mouth and other parts of their body. Sensory issues may affect oral motor skills, the ability of the parents to care for the child (e.g., dental and facial hygiene, feeding), and the willingness/ability of the child to eat a variety of tastes and textures or to wear certain clothes. Sensory integration issues may be important in expressive communication since producing communicative responses requires processing and integrating sensory input. Occupational therapy and/or feeding therapy are often helpful. Before age three, occupational and feeding therapy may be available through an early intervention program, and the focus will be teaching parents to work with the child in the home. However, not some early intervention programs consider feeding to be “medical” in nature and will not address these issues in which case the child will benefit from a private referral. An additional benefit will be the ongoing education about their child's abilities and how best to work with him or her. For older children, an occupational therapist will help with sensory integration issues and fine motor problems. Feeding therapists are either occupational or speech therapists with additional training in feeding; they can help with sensory issues around eating and swallowing. At school, occupational therapy can work with the student on self-help skills and other means to participate more fully in the academic program.

Oral Motor Impairments
Intervention for oral motor impairments may be critical during early development to facilitate adequate feeding. Subsequent interventions may be important to facilitate advancement in textures, improve drooling, and to develop expressive language. A swallow study should be done early if concerns for aspiration and repeated as skills change over time or new concerns arise. Feeding therapy may help with tolerating different foods and textures and safe swallowing.

Specialty Collaborations & Other Services

Physical Therapy (see Services below for local providers)

Helpful in designing/implementing programs in the home and at school for strength, coordination, and conditioning.

Occupational Therapy, Pediatric (see Services below for local providers)

Can provide evaluation and intervention to address fine motor and self-help skills.

Speech - Language Pathologists (see Services below for local providers)

Can provide evaluation and intervention to address oral motor skills as well as optimize communication (verbal or using augmentative approaches).

Disability Related Sports (see Services below for local providers)

Allows individuals with disabilities to participate in sports and recreational programs with support and adaptation of environment and equipment.

Early Intervention for Children with Disabilities/Delays (see Services below for local providers)

For children under 3 years. When there is an associated fee, private services funded through health insurance may cost less.

Public Schools (see Services below for local providers)

For children ages 3-21 years PT, OT, and speech-related services are provided to support mobility, fine motor and self-help skills, and communication for education-related goals, but not necessarily for medical goals (e.g., to enhance range of motion or improve feeding skills).

Development/Language

All children with DS have language deficits and will benefit from early referral for speech and language therapy. Children experience delays in both receptive and expressive speech. Often expressive language is substantially more delayed than receptive language. This is important to recognize as these children will benefit from alternate approaches to communication (e.g., sign). Speech disorders such as dysfluency, verbal apraxia, and articulation disorders are common. Up to 30% of children with DS will have autism however it is important not to assume that a child with DS who is not speaking has autism as there are many other reasons to have challenges with verbal output (e.g., verbal dyspraxia). Sensory integration issues factor into expressive communication, since producing communicative responses requires processing and integrating sensory input. Oral motor skills play a role in language development (see Development/Motor above). Intervention to provide appropriate stimuli and a bridge to verbal communication (though the use of an alternative communication method) is extremely important. Most children will require language support throughout their education.

The primary care clinician can help by:
  • Referring promptly to early intervention service providers
  • Ensuring appropriate hearing screening throughout childhood
  • Helping families understand the role of alternative communication methods. While 95% of children with DS will ultimately use verbal language, language acquisition is universally delayed. Alternative communication methods can help until this occurs and does not retard verbal language development. As soon as the child is able to produce words with efficiency, the child will prefer verbal communication.
  • Screen for signs and symptoms of autism and refer for additional evaluation if concern
  • Working with the family around behavioral issues that emerge due to limited communication and sensory aversions
  • Assisting in finding alternative supports when the early intervention or educational system is unable to meet the child's needs. Funding through private insurance, Medicaid, or other community programs may be available. Private referral may be appropriate for less “educational” goals (e.g., to work on a feeding disorder, drooling or oral aversion), since school-based services must relate to educational goals.
  • Keeping expectations high: Let families know that over half of children with DS learn to read and write. See Down Syndrome Misconceptions vs. Reality (Global Down Syndrome Foundation).

Specialty Collaborations & Other Services

Developmental Pediatrics (see Services below for local providers)

May be helpful to distinguish developmental from medical issues, guide referral or therapy, and to monitor progress.

Developmental Assessment (see Services below for local providers)

May include developmental pediatricians, neurologists, psychologists, speech and language pathologists, and occupational therapists. Can document current functional abilities and recommend optimal intervention programming.

Audiology (see Services below for local providers)

Can provide hearing screening, monitor hearing status, evaluate for and adjust amplification, and help families identify appropriate intervention services and adaptations.

Speech - Language Pathologists (see Services below for local providers)

Can provide evaluation and intervention to optimize communication (verbal or using augmentative approaches) and cognitive abilities.

Early Intervention for Children with Disabilities/Delays (see Services below for local providers)

Helpful from birth to age 3. When there is a fee, private services funded through health insurance may cost less.

Public Schools (see Services below for local providers)

Above age 3 years, most children with DS will qualify for services through the special education program offered by their local school district.

Complementary & Alternative Medicine

Many families of children with special health care needs utilize complementary and alternative medicine. Be sure to inquire about over-the-counter medications, herbs, nutritional supplements, and homeopathic remedies. Explain risks of using unregulated substances including various types of unregulated hormones. Identify possible interactions with prescription medications used by the child. Teaching the family a decision-making process when they are considering use of an alternative treatment will be helpful for them over the long term as they will face options repeatedly through the child’s life.

Chiropractic adjustments could be fatal if atlanto-axial instability is present. [La: 1990] In the medical literature there do not appear to be evidence-based protocols for chiropractic manipulation of patients with DS. Caution families who are considering chiropractic manipulation for their child.

Issues Related to Down Syndrome

Funding & Access to Care

Writing Letters of Medical Necessity

Ask the Specialist

The parents are overwhelmed with this child’s behavior, how do I help?

Contrary to some popular beliefs, many children with DS have very challenging behavior. Delays in development, anxiety, oppositional personalities, communication deficits, short attention span, limited impulse control, sensory concerns, and autism can be contributors. Start by trying to understand where the child functions (Are they 4 years old but functioning like a 2-year-old? Is this just the "terrible twos?") Ask the parent to describe specific events, which helps to give an understanding of contributing factors. Sometimes the child’s therapists or teachers can give insightf. (Can the child settle and focus during therapy? Are they acting out in the classroom and if so, what are the triggers?) If it is just the terrible twos in an older child, talk about that. If the child is primarily oppositional, parent training in behavioral techniques is helpful. If there are attention and impulse control issues or anxiety, depending on the severity, environmental supports, parent training for behavioral approaches, and sometimes medications are used. In some case, the child should be referred for an evaluation for autism.

Resources for Clinicians

On the Web

Council on Genetics, American Academy of Pediatrics
Supports the integration of genetic and genomic medicine in pediatric health care by expanding the genetic literacy of pediatric teams and supporting the professional needs of geneticists.

Trisomy 21 (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Helpful Articles

PubMed search for Down syndrome in children or adolescents, last year

Baumer N, Davidson EJ.
Supporting a happy, healthy adolescence for young people with Down syndrome and other intellectual disabilities: recommendations for clinicians.
Curr Opin Pediatr. 2014;26(4):428-34. PubMed abstract

Watts R, Vyas H.
An overview of respiratory problems in children with Down's syndrome.
Arch Dis Child. 2013;98(10):812-7. PubMed abstract

Clinical Tools

Clinical Checklists & Visit Tools

Down Syndrome Checklist (2018) (PDF Document 132 KB)
A checklist for recommended monitoring and screening of children with Down syndrome, adapted from the AAP guidelines by Bull et al.

Growth/BMI Charts

Down Syndrome Growth Charts (CDC)
Growth charts used on over 1500 measurements on 637 individual with DS, published by Zemel, et al. in 2015, from the Centers for Disease Control and Prevention's site.

Patient Education & Instructions

Children with Down Syndrome: Health Care Information for Families (AAP)
Guide to help parents and families of children with Down syndrome. Focuses on medical topics, by age, that affect physical health. PDF downloads available; American Academy of Pediatrics.

Living with Down Syndrome (Down Syndrome Educational Trust) (PDF Document 951 KB)
A 34-page, printable booklet with information about family, school, social, and medical issues particular to those with Down syndrome.

A Parent's Guide to Puberty for Children with Disabilities (LEND) (PDF Document 7 KB)
A toolkit for parents to help adolescents with disabilities learn about puberty, personal hygiene, acceptable public behavior, and peer relations; Vanderbilt Leadership Education in Neurodevelopmental Disabilities (LEND) long-term trainees.

Toilet Training Children with Down Syndrome (National Down Syndrome Society)
A guide to help determine toileting readiness and teach toileting skills to children with developmental disabilities. Includes simple images that may be used as visual cues.

Resources for Patients & Families

Where can I go for further information?

Information on the Web

Down Syndrome (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

Atlantoaxial Instability in Children with Down Syndrome (HealthyChildren.org)
Warning signs for compression of the spinal cord called atlantoaxial instability; American Academy of Pediatrics.

Down Syndrome - Health Issues
Site developed and edited/authored by a pediatrician, Len Leshin, MD, who has a son with Down syndrome. Includes a number of essays by experts about specific health topics and provides other useful links.

Down Syndrome Misconceptions vs. Reality (Global Down Syndrome Foundation)
The reality of misconceptions about Down syndrome.

The International Mosaic Down Syndrome Association
Aims to assist any family or individual whose life has been affected by mosaic Down syndrome.

What is Down Syndrome (National Down Syndrome Society )
An in-depth look at Down syndrome with information for children and adults.

Sexuality and People with Disabilities (PDF Document 257 KB)
This Medical Home newsletter provides information for primary care providers and families including Sexuality and People with Disabilities; American Academy of Pediatrics recommendations for education about sexuality; tips for parents; and resources, books, and websites for parents and providers.

Hearing and Vision Loss Associated with Down Syndrome (TSBVI)
An overview for families; Texas School for the Blind and Visually Impaired.

Dental Care for the Patient with Down Syndrome
Topics covered: Medical problems associated with Down syndrome that can affect dental treatment; proper home care and prevention of dental disease; techniques to help children with Down syndrome become cooperative dental patients; choosing the right dentist; and how to communicate effectively with the dental staff. by Dr. Elizabeth S. Pilcher, 1997, but still relevant.

National & Local Support

National Down Syndrome Congress
The NDSC, a membership organization, offers parent resources, including a "new parent package" of information, as well as news and events, government activities, and information on self-advocacy.

Studies/Registries

Clinical Trials in Children with Down Syndrome (clinicaltrials.gov)

DS-Connect: The Down Syndrome Registry (NIH)
Developed by the Down Syndrome Consortium, led by the National Institutes of Health and involving several Down syndrome advocacy and professional organizations, to offer opportunities for patients/families and researchers to connect and to allow access to research data by families.

Services for Patients & Families in Nevada

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Audiology

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Bone Densitometry/DEXA

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Dental Care Expense Assistance

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Developmental - Behavioral Pediatrics

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Developmental Assessment

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Developmental Pediatrics

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Disability Related Sports

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Early Intervention for Children with Disabilities/Delays

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General Dentistry

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Gynecology (Ped/Adol, Special Needs)

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Nutrition Assessment Services

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Occupational Therapy, Pediatric

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Orthodontics

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Pediatric Cardiology

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Pediatric Dentistry

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Pediatric Dermatology

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Pediatric Endocrinology

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Pediatric Gastroenterology

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Pediatric Genetics

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Pediatric Immunology/Rheumatology

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Pediatric Infectious Disease

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Pediatric Neurology

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Pediatric Neurosurgery

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Pediatric Ophthalmology

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Pediatric Orthopedics

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Pediatric Otolaryngology

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Pediatric Pulmonology

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Pediatric Rheumatology

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Pediatric Sleep Medicine

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Pediatric Urology

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Physical Therapy

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Psychiatrist, Child-18 (MD)

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Psychologist, Child-18 (PhD, PsyD)

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Public Schools

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Public Special Schools

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Speech - Language Pathologists

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For other services related to this condition, browse our Services categories or search our database.

Authors & Reviewers

Last update/revision: February 2019; initial publication: June 2013
Current Authors and Reviewers:
Author: Lisa Samson-Fang, MD
Authoring history
2018: update: Jennifer Goldman-Luthy, MD, MRP, FAAPCA
2013: first version: Lisa Samson-Fang, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

AAP.
AAP Publications Reaffirmed or Retired.
American Academy of Pediatrics; (2018) http://pediatrics.aappublications.org/content/141/5/e20180518. Accessed on 2/10/2019.

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The National Down Syndrome Cytogenetic Register (NDSCR).
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Population prevalence of Down's syndrome in the United Kingdom.
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American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal–Fetal Medicine.
Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders.
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Periodontal conditions in individuals with Down's syndrome.
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Supporting a happy, healthy adolescence for young people with Down syndrome and other intellectual disabilities: recommendations for clinicians.
Curr Opin Pediatr. 2014;26(4):428-34. PubMed abstract

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Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study.
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Boëchat MC, Silva KS, Llerena JC Jr, Boëchat PR.
Cholelithiasis and biliary sludge in Downs syndrome patients.
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Brouillette RT, Manoukian JJ, Ducharme FM, Oudjhane K, Earle LG, Ladan S, Morielli A.
Efficacy of fluticasone nasal spray for pediatric obstructive sleep apnea.
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An expert consensus panel of the American Academy of Pediatrics (AAP) published these guidelines for the care of children with Down syndrome in 2011, which were reaffirmed in January 2018.

Caird MS, Wills BP, Dormans JP.
Down syndrome in children: the role of the orthopaedic surgeon.
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Capone G, Goyal P, Ares W, Lannigan E.
Neurobehavioral disorders in children, adolescents, and young adults with Down syndrome.
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Capone GT, Brecher L, Bay M.
Guanfacine Use in Children With Down Syndrome and Comorbid Attention-Deficit Hyperactivity Disorder (ADHD) With Disruptive Behaviors.
J Child Neurol. 2016;31(8):957-64. PubMed abstract

Capone GT, Goyal P, Grados M, Smith B, Kammann H.
Risperidone use in children with Down syndrome, severe intellectual disability, and comorbid autistic spectrum disorders: a naturalistic study.
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Committee on Practice Bulletins—Obstetrics, Committee on Genetics, and the Society for Maternal-Fetal Medicine.
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Obstet Gynecol. 2016;127(5):e123-37. PubMed abstract

Committee on Practice and Ambulatory Medicine, Bright Futures Periodicity Schedule Workgroup.
2017 Recommendations for preventive pediatric health care.
Pediatrics. 2017;139(4). PubMed abstract / Full Text
Includes a link to the Periodicity Schedule, https://www.aap.org/en-us/Documents/periodicity_schedule.pdf.

Dixon N, Kishnani PS, Zimmerman S.
Clinical manifestations of hematologic and oncologic disorders in patients with Down syndrome.
Am J Med Genet C Semin Med Genet. 2006;142C(3):149-57. PubMed abstract

Dixon NE, Crissman BG, Smith PB, Zimmerman SA, Worley G, Kishnani PS.
Prevalence of iron deficiency in children with Down syndrome.
J Pediatr. 2010;157(6):967-971.e1. PubMed abstract / Full Text

Downes A, Anixt JS, Esbensen AJ, Wiley S, Meinzen-Derr J.
Psychotropic Medication Use in Children and Adolescents With Down Syndrome.
J Dev Behav Pediatr. 2015;36(8):613-9. PubMed abstract

Durmowicz AG.
Pulmonary edema in 6 children with Down syndrome during travel to moderate altitudes.
Pediatrics. 2001;108(2):443-7. PubMed abstract
of particular relevance perhaps in Utah.

Dykens EM.
Psychiatric and behavioral disorders in persons with Down syndrome.
Ment Retard Dev Disabil Res Rev. 2007;13(3):272-8. PubMed abstract

Farhood Z, Isley JW, Ong AA, Nguyen SA, Camilon TJ, LaRosa AC, White DR.
Adenotonsillectomy outcomes in patients with Down syndrome and obstructive sleep apnea.
Laryngoscope. 2017;127(6):1465-1470. PubMed abstract

Gillespie KM, Dix RJ, Williams AJ, Newton R, Robinson ZF, Bingley PJ, Gale EA, Shield JP.
Islet autoimmunity in children with Down's syndrome.
Diabetes. 2006;55(11):3185-8. PubMed abstract

Ieiri S, Higashi M, Teshiba R, Saeki I, Esumi G, Akiyoshi J, Nakatsuji T, Taguchi T.
Clinical features of Hirschsprung's disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan.
J Pediatr Surg. 2009;44(12):2347-51. PubMed abstract

Juj H, Emery H.
The arthropathy of Down syndrome: an underdiagnosed and under-recognized condition.
J Pediatr. 2009;154(2):234-8. PubMed abstract

Keeling LA, Spiridigliozzi GA, Hart SJ, Baker JA, Jones HN, Kishnani PS.
Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.
Am J Med Genet A. 2017;173(11):3058-3066. PubMed abstract

La Francis ME.
A chiropractic perspective on atlantoaxial instability in Down's syndrome.
J Manipulative Physiol Ther. 1990;13(3):157-60. PubMed abstract

Lin AE, Basson CT, Goldmuntz E, Magoulas PL, McDermott DA, McDonald-McGinn DM, McPherson E, Morris CA, Noonan J, Nowak C, Pierpont ME, Pyeritz RE, Rope AF, Zackai E, Pober BR.
Adults with genetic syndromes and cardiovascular abnormalities: clinical history and management.
Genet Med. 2008;10(7):469-94. PubMed abstract / Full Text

Lott IT.
Neurological phenotypes for Down syndrome across the life span.
Prog Brain Res. 2012;197:101-21. PubMed abstract / Full Text

Macchini F, Leva E, Torricelli M, Valadè A.
Treating acid reflux disease in patients with Down syndrome: pharmacological and physiological approaches.
Clin Exp Gastroenterol. 2011;4:19-22. PubMed abstract / Full Text

Menéndez M.
Down syndrome, Alzheimer's disease and seizures.
Brain Dev. 2005;27(4):246-52. PubMed abstract

Mik G, Gholve PA, Scher DM, Widmann RF, Green DW.
Down syndrome: orthopedic issues.
Curr Opin Pediatr. 2008;20(1):30-6. PubMed abstract

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Down syndrome and the enteric nervous system.
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Morris JK, Alberman E.
Trends in Down's syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register.
BMJ. 2009;339:b3794. PubMed abstract / Full Text

Murphy NA, Elias ER.
Sexuality of children and adolescents with developmental disabilities.
Pediatrics. 2006;118(1):398-403. PubMed abstract / Full Text
This American Academy of Pediatrics' Clinical Report provides additional information and guidance for providers relating to puberty, psychosocial considerations, sexual abuse, sexuality education, and the pediatrician's role.

Nation J, Brigger M.
The Efficacy of Adenotonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review.
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Oxelgren UW, Myrelid Å, Annerén G, Ekstam B, Göransson C, Holmbom A, Isaksson A, Åberg M, Gustafsson J, Fernell E.
Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study.
Dev Med Child Neurol. 2017;59(3):276-283. PubMed abstract

Pavlovic M, Berenji K, Bukurov M.
Screening of celiac disease in Down syndrome - Old and new dilemmas.
World J Clin Cases. 2017;5(7):264-269. PubMed abstract / Full Text

Plaiasu V.
Down Syndrome - Genetics and Cardiogenetics.
Maedica (Buchar). 2017;12(3):208-213. PubMed abstract / Full Text

Richalet JP, Chenivesse C, Larmignat P, Meille L.
High altitude pulmonary edema, down syndrome, and obstructive sleep apneas.
High Alt Med Biol. 2008;9(2):179-81. PubMed abstract

Taşdemir HA, Cetinkaya MC, Polat C, Belet U, Kalayci AG, Akbaş S.
Gallbladder motility in children with Down syndrome.
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Unachak K, Tanpaiboon P, Pongprot Y, Sittivangkul R, Silvilairat S, Dejkhamron P, Sudasna J.
Thyroid functions in children with Down's syndrome.
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Viegelmann G, Low Y, Sriram B, Chu HP.
Achalasia and Down syndrome: a unique association not to be missed.
Singapore Med J. 2014;55(7):e107-8. PubMed abstract / Full Text

Walker JC, Dosen A, Buitelaar JK, Janzing JG.
Depression in Down syndrome: a review of the literature.
Res Dev Disabil. 2011;32(5):1432-40. PubMed abstract

Watts R, Vyas H.
An overview of respiratory problems in children with Down's syndrome.
Arch Dis Child. 2013;98(10):812-7. PubMed abstract

Worley G, Crissman BG, Cadogan E, Milleson C, Adkins DW, Kishnani PS.
Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome.
J Child Neurol. 2015;30(9):1147-52. PubMed abstract

Worley G, Shbarou R, Heffner AN, Belsito KM, Capone GT, Kishnani PS.
New onset focal weakness in children with Down syndrome.
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Estimation of the number of people with Down syndrome in the United States.
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