Overview

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.


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

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.

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.

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) ( 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) ( 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:

• Esophageal dysmotility including achalasia [Viegelmann: 2014]
• Gastro-esophageal reflux disease [Macchini: 2011]
• Constipation or intermittent diarrhea [Pavlovic: 2017]
• Gallstones [Boëchat: 2007] [Taşdemir: 2004]
• Celiac disease. (~5%) Note that about a third of individuals with Down syndrome and celiac disease have no overt clinical symptoms. [Bull: 2011] [Pavlovic: 2017] See Celiac Disease for more detail.

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:

• Celiac disease (~5%): [Bull: 2011] [Book: 2001] Note that about a third of individuals with Down syndrome and celiac disease have no overt clinical symptoms. [Pavlovic: 2017] See Celiac Disease for more detail.

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

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

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.

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.

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

Funding & Access to Care

Writing Letters of Medical Necessity

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 Checklists & Visit Tools

Down Syndrome Checklist (2018) ( 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) ( 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) ( 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.

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 ( 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 (NV)

Service Categories	# of providers* in:	NV	NW	Other states (5)  (show)		ID	MT	NM	RI	UT
Audiology		6	1		33	48	300	20	51
Bone Densitometry/DEXA							4		1
Dental Care Expense Assistance		4			1	1	19	3	16
Developmental - Behavioral Pediatrics		3	1		2	6	4	15	8
Developmental Assessment		1			144	11	265	29	46
Disability Related Sports			3		4	5	16	12	46
Early Intervention for Children with Disabilities/Delays		24	2		150	22	216	12	54
General Dentistry		19			105	251	8	6	152
Gynecology (Ped/Adol, Special Needs)					2				21
Nutrition Assessment Services		11			104	2	171	3	20
Occupational Therapy, Pediatric		10			23	34	301	7	35
Orthodontics		4				49	6		22
Pediatric Cardiology		2	1		4	16	47	15	4
Pediatric Dentistry		24			59	47	77	21	61
Pediatric Dermatology			1			2	2	1	1
Pediatric Endocrinology		4	1		1	13	27	14	4
Pediatric Gastroenterology		5	1		2	20	5	18	3
Pediatric Genetics		2			3	6		4	5
Pediatric Immunology/Rheumatology					1	3		1	3
Pediatric Infectious Disease		2			1	1		4	1
Pediatric Neurology		7			3	14	33	17	4
Pediatric Neurosurgery		4	1		1	1		1	1
Pediatric Ophthalmology		5	1		8	14	8	7	6
Pediatric Orthopedics		4	1		2	11	10	10	16
Pediatric Otolaryngology		4	1		3	4		7	9
Pediatric Pulmonology		5			1	6	5	10	4
Pediatric Rheumatology		1	1				3
Pediatric Sleep Medicine					3	2		1	3
Pediatric Urology		13			1	5	4	1	2
Physical Therapy		18			30	34	363	3	60
Psychiatrist, Child-18 (MD)		14			9	17	23	135	25
Psychologist, Child-18 (PhD, PsyD)					7	11	3	19	143
Public Schools		4						18	11
Public Special Schools		2				1	15	2	19
Speech - Language Pathologists		14	3		68	46	418	16	65

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

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

Alberman E.
The National Down Syndrome Cytogenetic Register (NDSCR).
J Med Screen. 2002;9(3):97-8. PubMed abstract

Alexander M, Ding Y, Foskett N, Petri H, Wandel C, Khwaja O.
Population prevalence of Down's syndrome in the United Kingdom.
J Intellect Disabil Res. 2016;60(9):874-8. PubMed abstract

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.
Obstet Gynecol. 2016;127(5):e108-22. PubMed abstract

Aumonier ME, Cunningham CC.
Breast feeding in infants with Down's syndrome.
Child Care Health Dev. 1983;9(5):247-55. PubMed abstract

Bagić I, Verzak Z, Cuković-Cavka S, Brkić H, Susić M.
Periodontal conditions in individuals with Down's syndrome.
Coll Antropol. 2003;27 Suppl 2:75-82. PubMed abstract

Barca D, Tarta-Arsene O, Dica A, Iliescu C, Budisteanu M, Motoescu C, Butoianu N, Craiu D.
Intellectual disability and epilepsy in down syndrome.
Maedica (Buchar). 2014;9(4):344-50. PubMed abstract / Full Text

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

Bertapelli F, Pitetti K, Agiovlasitis S, Guerra-Junior G.
Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: A literature review.
Res Dev Disabil. 2016;57:181-92. PubMed abstract

Bocian AB, Wasserman RC, Slora EJ, Kessel D, Miller RS.
Size and age-sex distribution of pediatric practice: a study from Pediatric Research in Office Settings.
Arch Pediatr Adolesc Med. 1999;153(1):9-14. PubMed abstract

Book L, Hart A, Black J, Feolo M, Zone JJ, Neuhausen SL.
Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study.
Am J Med Genet. 2001;98(1):70-4. PubMed abstract

Boëchat MC, Silva KS, Llerena JC Jr, Boëchat PR.
Cholelithiasis and biliary sludge in Downs syndrome patients.
Sao Paulo Med J. 2007;125(6):329-32. PubMed abstract

Brouillette RT, Manoukian JJ, Ducharme FM, Oudjhane K, Earle LG, Ladan S, Morielli A.
Efficacy of fluticasone nasal spray for pediatric obstructive sleep apnea.
J Pediatr. 2001;138(6):838-44. PubMed abstract

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
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.
J Am Acad Orthop Surg. 2006;14(11):610-9. PubMed abstract

Capone G, Goyal P, Ares W, Lannigan E.
Neurobehavioral disorders in children, adolescents, and young adults with Down syndrome.
Am J Med Genet C Semin Med Genet. 2006;142C(3):158-72. PubMed abstract

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.
J Dev Behav Pediatr. 2008;29(2):106-16. PubMed abstract

Committee on Practice Bulletins—Obstetrics, Committee on Genetics, and the Society for Maternal-Fetal Medicine.
Practice Bulletin No. 163: Screening for Fetal Aneuploidy.
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

Moore SW.
Down syndrome and the enteric nervous system.
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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.
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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.

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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.
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Pavlovic M, Berenji K, Bukurov M.
Screening of celiac disease in Down syndrome - Old and new dilemmas.
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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.
J Pediatr Gastroenterol Nutr. 2004;39(2):187-91. PubMed abstract

Unachak K, Tanpaiboon P, Pongprot Y, Sittivangkul R, Silvilairat S, Dejkhamron P, Sudasna J.
Thyroid functions in children with Down's syndrome.
J Med Assoc Thai. 2008;91(1):56-61. PubMed abstract

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.
Am J Med Genet A. 2004;128A(1):15-8. PubMed abstract / Full Text

de Graaf G, Buckley F, Skotko BG.
Estimation of the number of people with Down syndrome in the United States.
Genet Med. 2017;19(4):439-447. PubMed abstract