Other Names

Trisomy 21
Down's syndrome
Translocation Down syndrome
Mosaic Down syndrome

Diagnosis Coding

Description

Down syndrome (DS), also commonly known as trisomy 21, is the most common genetic disorder causing intellectual disability and the most frequently occurring human chromosomal syndrome. Several physical characteristics are common to individuals with DS, particularly features of the face, hands, and feet. Numerous other congenital anomalies occur with increased frequency in DS, such as endocardial cushion defects, intestinal atresias, and Hirschsprung disease. A number of acquired conditions also occur with increased frequency, such as hypothyroidism, hearing impairment, and celiac disease.

Prevalence

The overall prevalence of DS is 1/732 (1.3/1000). [Canfield: 2006] An estimated 5,500 infants with DS are born annually in the United States. The risk of conceiving an infant with DS is related to maternal age – the risk of DS with each pregnancy is 1/1,600 for women less than 25 years of age, 1/250 for women age 35-39 years, and 1/40 for women greater than 42 years of age. Because a large majority of babies are born to younger women, the majority of babies with DS,are born to women under the age of thirty, even though the risk per pregnancy is higher in older women. With the advent of universal prenatal screening, the incidence of trisomy 21 may decline, as has been observed in some European countries. [Morris: 2009]

Genetics

In the majority of individuals with trisomy 21, the additional chromosome results from nondisjunction of chromosome 21 during meiosis (>90% are of maternal origin). A small percentage (4%) of DS results from a translocation, with attachment of the long arm of an extra chromosome 21 to another chromosome. An additional small percentage results from nondisjunction during mitosis of the fertilized egg, resulting in mosacism.

Prognosis

There is wide variability in the degree of associated cognitive disability and social adaptability. Scientific advances in health care 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 Down syndrome. With the aid of a job coach, many adults with DS are employed in the private sector.

Based on data from the West Australian birth defects registry, approximately 4% of live born infants with trisomy 21 die within the first year of life and an additional 7% die before 18 years of age. [Leonard: 2000] There is a strong correlation between congenital heart defects and death during the first 10 years of life. Pneumonia and other respiratory infections are also a primary cause for mortality. Nearly one third of individuals with trisomy 21 will live into or beyond their fifties.

Roles Of The Medical Home

For the child with DS, the Medical Home should provide treatment of acute illness, as well as well child and chronic care visits at which preventive services are provided and progress and problems can be reviewed and managed proactively. Treatment guidelines are available for the care of children with DS and the Medical Home is pivotal in implementing recommended screening, evaluations, and interventions. Children with DS often require the attention of sub-specialists and the Medical Home should initiate and coordinate these visits in collaboration with the family. The management of DS focuses on maximizing the child's capabilities at home and in the community. Treatment should be interdisciplinary and start as early as possible. Specific goals include optimizing growth and development and providing ongoing information to families regarding available interventions, relevant community resources, evolving scientific understanding of trisomy 21, and emerging treatments.

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

Helpful Articles

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

Overview

The health care of children with trisomy 21 begins with identification of the condition (based upon in utero screening or recognition of clinical features after delivery), confirmation of the diagnosis, identification of associated birth defects, and counseling families regarding the etiology of DS, range of outcomes, services available to optimize outcomes, and recurrence risk.  

For The Condition

Current guidelines for screening for fetal trisomy 21 include offering all women diagnostic testing for fetal aneuploidy by chorionic villus sampling (CVS), if available, or amniocentesis.  First trimester screening for pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), and, if available, nuchal translucency (NT) assessment is acceptable for women presenting early in pregnancy. Regardless of the results of chromosome analysis or biochemical screening, all women who have an elevated NT should be offered a detailed anatomic ultrasound, echocardiogram, or both. Women presenting for prenatal care at the second trimester should be offered multiple marker screening; those who had trisomy 21 screening in the first trimester and/or CVS/amniocentesis should be offered maternal serum alpha-fetoprotein screening and/or an anatomic survey between 16 and 20 weeks gestation to detect neural tube defects. The use of first and second trimester screening have improved detection rates and lowered false positive rates; adequate systems to manage screening protocols, disclosure/non-disclosure requests, and counseling for individualized decision-making is critical.[Driscoll: 2008]

Of Family Members

If a child with trisomy 21 is determined to have a chromosomal translocation, it important to determine if the parents carry a balanced translocation, since this impacts recurrence risks.

For Complications

Current guidelines [Bull: 2011] recommend screening for thyroid disorders, hearing impairments, visual concerns, celiac disease, sleep apnea, dysphagia, iron deficiency anemia, and atlanto-axial instability

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 an infant with DS that was not previously identified is becoming less common but will continue to occur. Clinicians ask "does this child have Down syndrome?" 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 over half of these not until adulthood (note 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 the majority of 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

Since many physical features of DS occur occasionally in typical infants, the clinician should look for a constellation of findings when considering the diagnosis. Nevertheless, diagnostic confusion can occur – in one laboratory's review, among blood samples obtained by clinicians to confirm or exclude trisomy 21, 28% had a normal karyotype. [Devlin: 2004] Epicanthal folds, protruding tongue, simian crease, widely-spaced first and second toes, hypotonia, and up-slanting palpebral fissures were physical findings that raised concern in the karyotypically normal infants. Confusing DS with another genetic syndrome is uncommon but can occur, since its features can overlap with other syndromes (e.g., Smith-Magenis syndrome, Noonan syndrome). These issues underscore the importance of genetic testing to confirm diagnosis.

Comorbid Conditions

Individuals with Down syndrome are at risk for a number of associated conditions, discussed below by organ system.

Cardiovascular

Congenital heart defects are found in 44% of infants with DS. Early mortality is associated with the presence of a cardiac defect, particularly if combined with a gastrointestinal malformation. The following occur with increased frequency in DS:

• 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 tetrology of Fallot (4%)
• Other (1%)
  
  

Acquired Valvular Dysfunction is common in adults without congenital heart disease (up to 50%), with mitral valve prolapse being the most common. Tricuspid, aortic, and mitral insufficiency have also been reported. 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]

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 and, in the patient with a unrepaired heart defect, Eisenmenger syndrome may evolve.

Nutrition

• Newborns with DS are at risk for feeding problems due to a weak suck and problems related to any organ malformations. However, the majority of mothers who breast feed are successful. [Aumonier: 1983] 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 generalized hypotonia.
• Older children are at risk for excessive weight gain. [Grammatikopoulou: 2008]
• Behavioral feeding concerns, celiac disease, 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. Contributing factors may include:

• Structural abnormalities – midface hypoplasia, large tongue, small subglottic area, laryngomalacia, narrow nasopharynx, tracheobronchomalacia, and tracheal stenosis)
• 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.
• Cardiac conditions
• Gastro-esophageal reflux or dysphagia leading to aspiration

A case series of high altitude pulmonary edema was reported that included 6 children with DS [Durmowicz: 2001].  Some of these children had underlying congenital heart defects and/or pulmonary hypertension. It is unclear if children with trisomy 21 have an increased risk of altitude sickness but the authors of the case series suggested that care be taken when traveling to moderate altitudes with children with DS, particularly those with obstructive sleep apnea that might contribute to altered chemoresponsiveness to hypoxia.

Sleep

Sleep apnea occurs in up to 45% of children with DS. Contributing factors may include: structural abnormalities (as mentioned under Respiratory above), tonsillar/adenoidal hyperplasia, hypotonia, obesity, and brainstem dysfunction. Symptoms 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
  
  

Gastrointestinal

The incidence of a gastrointestinal malformation in DS is approximately 5%. The most common are: tracheoesophageal fistula, duodenal obstruction, annular pancreas, imperforate anus, and Hirschsprung Disease. Individuals with DS are also at higher risk for:

• Esophageal dysmotility
• Gastro-esophageal reflux disease
• Constipation
• Gallstones
• Celiac disease. Up to 20% of individuals with DS and celiac disease have no overt clinical symptoms. [Book: 2001] Screening for symptoms that may be related to celiac disease in children with DS at yearly visits and serologic screening if symptoms are present. See the Celiac Disease module for more detail.

Hematologic  Neonates with trisomy 21 can have transient asymptomatic blood count abnormalities including neutrophilia, thrombocytopenia, and polycythemia. 10% of infants with DS develop transient myeloproliferative disease (characterize by the presence of blasts on the smear) with spontaneous regresssion in the vast majority transient myeloproliferative disease can itself cause significant morbidity/mortality due to rare liver/heart failure, sepsis, DIC, and hyperviscosity. However up to 20% of children with DS and myeloproliferation develop myeloid leukemia (often delayed with a mean age onset of 20 months) and monitoring for resolution of the myeloproliferation (and continued intermittent monitoring until 3 years of age) is indicated in children who have had transient myeloproliferation.  

Children with DS are at an increased risk of leukemia throughout childhood. Despite the increased incidence, the development of leukemia is still a relatively rare event and routine screening (beyond a complete blood count with differential at birth) is not recommended.

Guidelines recommend yearly monitoring of hemoglobin and for risk factors of iron deficiency with a CRP/ferritin (or reticulocyte hemoglobin) obtained yearly if any risk factors are present.

Neurology

• Microcephaly – Is relatively common in trisomy 21. Neuroimaging may be considered in those with severe microcephaly. Although the current guidelines do not recommend use of the previously derived DS growth charts to monitor growth, they remain the only published standard that a clinician might use to determine the extent to which a child head circumference is below that typically observed in trisomy 21.
• Seizures – the prevalence of seizures in children with DS is 8%. Seizure type may include generalized tonic-clonic seizures, partial seizures, and infantile spasms. Of note, about 13% of children with DS and no clinical seizures have EEG abnormalities that may complicate interpretation. The following articles offer useful information specific to children with DS: [Goldberg-Stern: 2001], [Stafstrom: 1994], [Quinlivan: 2005].
• New-onset weakness – 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), and brachial plexus injury. [Worley: 2004] Urgent neurology consultation is indicated for new-onset focal weakness.
• Dementia – Alzheimer-type neuropathologic abnormalities are found in patients with DS, with or without clinical dementia. More than half of individuals older than 50 years develop Alzheimer's disease (AD).
• Myelopathy may result from AAI or subluxation of the occiput on C1 due to the ligamentous laxity seen in some patients with trisomy 21.  Current evidence does not support the use of screening x-rays in asymptomatic children as they have proven to be sensitive or specific to development of myelopathy. 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) and instructed to seek care if signs/symptoms emerge.  Families should understand that participation in certain sports (gymnastics, football, soccer, diving) may carry a higher risk of spinal cord injury and that use of a trampoline is not recommended.  Families should also be educated about positioning precautions for all children at risk for AAI during anesthesia/sedation, surgical procedures, and radiographic examinations.  At yearly visits, medical home providers should reinforce this information and perform a neurologic exam monitoring for any signs of myelopathy (increased tone, brisk reflexes, clonus, positive Babinski).  If signs or symptoms 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 in this area.  Special Olympics has their own set of screening guidelines and, at the time of this publication, require screening neck x-rays to participate.
  
  

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 Neurobehavioral Disorders in Children, Adolescents, and Young Adults with Down Syndrome. [Capone: 2006] Other sections of the Medical Home Portal may be helpful, including those on Autism Spectrum Disorder, Depression, and Attention Deficit Hyperactivity Disorder (ADHD).

Attention Deficit Disorder - Concerns about focus, attention span, activity level and/or impulsiveness are common. 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? by Dianne McBrien, MD, a developmental pediatrician at Children's Hospital of Iowa.

Autism - The prevalence of autism spectrum disorders (ASD) is 5-10% in children with DS and is more common in boys than girls. [Capone: 2005] 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.

Ears/Hearing

Individuals with DS are at risk for hearing loss which may be sensorineural, conductive, or mixed in etiology. By adulthood, 60-80% have hearing loss. During early development, even minor hearing impairment can negatively impact language and cognitive development.

Children with DS have a high incidence of sino-pulmonary disease, including recurrent/chronic sinusitis and otitis. 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. Tympanometry may be helpful in the cooperative child. Consider referral to an otolaryngologist for monitoring if the middle ear cannot be adequately visualized or if the child has recurrent sinus or ear infections. Children with DS may also have auditory processing deficits that affect word perception, short term auditory memory, and sequential auditory memory. If a family, child, or teacher suspects auditory processing difficulties, referral to an audiologist for evaluation may be indicated. 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:

• Nystagmus
• Strabismus (42%, usually acquired)
• Far-sightedness
• Near-sightedness
• Accommodative weakness
• Amblyopia (22%)
• Keratoconus (cone-shaped cornea)
• Congenital cataracts
• Blepharitis
• Conjunctivitis
• Lacrimal duct obstruction
• Retinal abnormalities

The following may be helpful for families: Hearing and Vision Loss Associated with Down Syndrome (TSBVI) and National Keratoconus Foundation.

Dental

Children and young adults with DS are at risk for:

• Significant delay in eruption of both primary and secondary teeth
• Missing and/or malformed teeth
• 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 in DS. Screening with a TSH is indicated in the newborn period, at 6 months, 12 months, and then yearly. Some experts recommend measuring thyroxine level (free T4) along with TSH. [American: 2001] [Unachak: 2008] [Rose: 2006]  In the event of a mildly elevated TSH with a normal free T4, measurement of thyroid antibodies may help to identify those with euthyroid Hashimoto’s thyroiditis who may be more likely to progress to hypothyroidism over time. Of those with subclinical thyroid disease, only a minority will progress to hypothyroidism and no consensus exists on the need to treat subclinical hypothyroidism.

Autoimmune Disorders

The following are associated with DS:

• Hashimoto's thyroiditis [Unachak: 2008]
• Alopecia areata
• Auto-immune adrenalitis
• Pernicious anemia
• Vitiligo
• Diabetes mellitus [Gillespie: 2006]
• Autoimmune hepatobiliary disease (chronic active hepatitis, primary sclerosing cholangitis)
• Juvenile idiopathic arthritis [Juj: 2009]
• Celiac disease [Book: 2001]

A number of 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 celiac disease.

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 DS show evidence of atlanto-axial instability (AAI) on x-ray, only 1-2% have symptoms that require treatment. The value of screening for upper cervical spine instability has been questioned. [American: 1995]  Although, little is known about the positive and negative predictive values of screening x-rays, they are no longer recommended by the AAP and but currently are required by the Special Olympics for participation. The normal atlas-dens interval is less than 3.5mm in children but may normally reach 5mm in children with DS. 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. The yearly physical should include examination of reflexes, including the Babinski. A child with symptoms should have immediate evaluation. 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

Relevant citations: [Bull: 2011]

Dermatologic

Individuals with DS are at risk for:

• Alopecia areata:  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.
• 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

While not part of the AAP recommendations, some experts recommend routine screening of infants with DS with renal ultrasonography and, if abnormal, a voiding cystourethrogram. [Mercer: 2004] Any child with DS and urinary symptoms (e.g., UTI, difficulty with voiding, unexplained enuresis) should have evaluation of the urinary tract. Testicular examination during yearly physical exam is important, particularly in patients unlikely to do self-exams.

Pearls & Alerts

Sleep apnea occurs in up to 45% of individuals with DS.

The etiology may be obstructive, central, or mixed. A subset of individuals exhibit clinically significant sleep apnea without overt signs of upper airway obstruction. See Sleep under Co-Morbid Conditions below.

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. See below under CoMorbid Conditions for more detail.

The initial evaluation of the child with suspected Down syndrome 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.

Family History

A three-generation pedigree is indicated, though a family history of DS or other 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 Or 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), and detection of structural defects (including the prenatal diagnosis by ultrasound of cardiovascular malformations or duodenal atresia). The perinatal history is usually uncomplicated.

Current & Past Medical History

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

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. 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.
Review supports the child is receiving through early intervention, the school district, or private therapy providers, the child’s rate of progress, parents’ satisfaction with current services, and the family’s concerns regarding development or functional goals. Skills in activities of daily living, eating, and community integration should be discussed. If a child with DS is not making progress or his/her developmental pattern falls outside the expected, additional evaluation is indicated to identify comorbid conditions (e.g., verbal or motor apraxia, hearing impairment, autism, impairments in focus, neurologic conditions).

Behavior challenges are common, including sleep and feeding concerns, internalizing/externalizing behaviors, and 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. 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. Ask family members if they have known someone with DS may uncover 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 work force 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.

Physical Exam

Sensory Testing

Vision: Following a normal routine newborn examination, the AAP suggests consideration of referral to an ophthalmologist within the 6 months of life. Follow up with a pediatric ophthalmologist, or general ophthalmologist familiar with DS, should occur annually from 1 to 5, every 2 years from 6 to 13, and every three years from 14 to 21.

Hearing: AAP guidelines [Bull: 2011] suggest:

• Hearing be tested by an objective method (e.g., otoacoustic emissions) at birth
• Assessment by history at every well child visit
• Assessment "by objective method" at 6 months, 12 months, and annually through age 21.
• Attempt first behavioral audiogram by 1 year and insure assessment of ear specific hearing as soon as child is able.
• Objective hearing assessment should also be considered whenever there is parental concern or evidence of persistent middle ear effusions.

Laboratory Testing

AAP screening guidelines recommend:

• Thyroid stimulating hormone at newborn screen, 6 months, and annually
• Celiac testing (e.g., TTG IgA and serum IgA) if any suggestive symptoms
• Complete blood count with differential in the newborn period to screen for myeloproliferative disorder and polycythemia
• Hemoglobin annually
• Ferritin/CRP (or reticulocyte hemoglobin): annually if risk factor for iron deficiency or if hemoglobin less than 11

Imaging

• Echocardiogram should be performed on every child 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 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."
• Consider a KUB in any newborn in a 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.
• An “unprepped” barium enema for any concern for Hirschsrung disease.
• Neuroimaging is not routinely indicated, but should be considered in a child with macrocephaly or 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 can not be attributed to DS.

Genetic Testing

A karyotype performed on lymphocytes confirms the diagnosis and is important to clarify which of the chromosome abnormalities (parental nondisjunction of chromosome 21, translocation or mosaicism) is the cause. Studies are done on the parents only if there is a translocation present in the child. Prenatal diagnosis in future pregnancies, either with chorionic villous sampling at 10 weeks or amniocentesis at 15 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).

Other Testing

Sleep Study: If any symptoms of obstructive sleep apnea are noted, a sleep study should be obtained. Guidelines call for a sleep study by 4 years of age in all affected children.

Modified Barium Swallow (MBS): guidelines recommend evaluating for aspiration with a MBS in any infant with suggestive symptoms, including marked hypotonia, slow feeding, choking, recurrent/persistent respiratory symptoms, or failure to thrive.

Subspecialist Collaborations & Other Resources

Overview

There is no treatment for the underlying genetic abnormality in Down syndrome (DS) – treatment focuses on the management of specific comorbid conditions as outlined above.

Systems

These frequently asked questions are adapted from Down Syndrome Frequently Asked Questions.

Recreation & Leisure

Adapted Athletic Programs

Information for Clinicians

Committee on Genetics, American Academy of Pediatrics
Committee on Genetics studies and makes recommendations to the Board of Directors on recent advances in genetics and provides support to chapters on state legislative issues as they relate to genetics.

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

Clinical Checklists & Visit Tools

Down Syndrome Checklist (2013) ( 125 KB)
A checklist for recommended monitoring and screening of children with Down syndrome. Included in appendix 1 of the AAP Trisomy 21 treatment guidelines.

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 (AAP).

A Parent's Guide on Puberty for Children with Disabilities ( 7 KB)
A toolkit for parents to use as they choose, this publication was developed and written by Vanderbilt Leadership Education in Neurodevelopmental Disabilities (LEND) long-term trainees.

Dental Care for the Patient with Down Syndrome
Topics covered are: Medical problems associated with Down syndrome that can affect dental treatment; proper home care and prevention of dental diseaset; 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.

Toilet Training Children with Down Syndrome (National Down Syndrome Society)
The NDSS offers this guide on their website as a guide to determine toileting readiness and teaching toileting skills. Includes simple images that may be used as visual cues. This guide may be helpful in teaching toileting skills to any child with a developmental disability.

Down Syndrome (Genetic Science Learning Center)
A brief educational overview of the genetics of Down syndrome from the Genetic Science Learning Center at the University of Utah.

Toolkits

Health Care for Adults with Intellectual & Developmental Disabilities - Toolkit for Primary Care Providers (Vanderbilt)
Online compilation of knowledge resources, checklists, "Health Watch Tables" for autism, Down syndrome, fragile X, Prader-Willi, Williams syndrome, and 22q11.2 deletion syndrome, and other resources to support the adult primary care (and transition thereto) of individuals with developmental and intellectual disabilities; from the Vanderbilt Kennedy Center for Excellence in Developmental Disabilities.

Down Syndrome

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.

Down Syndrome (MedlinePlus)
From the National Library of Medicine and National Institutes of Health, offers many links to high-quality sources of information for patients and their families.

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 Resources: Washington State
The Center for Children with Special Needs provides various resources for specific conditions, including Down syndrome.

Living with Down Syndrome (Down Syndrome Educational Trust) ( 951 KB)
This 34-page document provides information about Down syndrome; family and school issues; People First and cultural issues.

Support National & Local

International Foundation for Genetic Research (The Michael Fund)
Advocacy organization aimed at fund-raising for research, improving care and education of children with Down syndrome, and right-to-life issues.

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.

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

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

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

Authors

American Academy of Pediatrics - Committee on Genetics.
Health supervision for children with Down syndrome.
Pediatrics. 2001;107(2):442-9. PubMed abstract / Full Text

American Academy of Pediatrics Committee on Sports Medicine and Fitness.
Atlantoaxial instability in Down syndrome: subject review. American Academy of Pediatrics Committee on Sports Medicine and Fitness.
Pediatrics. 1995;96(1 Pt 1):151-4. 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

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

Bower CM, Richmond D.
Tonsillectomy and adenoidectomy in patients with Down syndrome.
Int J Pediatr Otorhinolaryngol. 1995;33(2):141-8. 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 2017.

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

Canfield MA, Honein MA, Yuskiv N, Xing J, Mai CT, Collins JS, Devine O, Petrini J, Ramadhani TA, Hobbs CA, Kirby RS.
National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001.
Birth Defects Res A Clin Mol Teratol. 2006;76(11):747-56. 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, 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

Capone GT, Grados MA, Kaufmann WE, Bernad-Ripoll S, Jewell A.
Down syndrome and comorbid autism-spectrum disorder: characterization using the aberrant behavior checklist.
Am J Med Genet A. 2005;134(4):373-80. PubMed abstract

Devlin L, Morrison PJ.
Accuracy of the clinical diagnosis of Down syndrome.
Ulster Med J. 2004;73(1):4-12. PubMed abstract / Full Text

Driscoll DA, Gross SJ.
First trimester diagnosis and screening for fetal aneuploidy.
Genet Med. 2008;10(1):73-5. 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.

Geggel RL, O'Brien JE, Feingold M.
Development of valve dysfunction in adolescents and young adults with Down syndrome and no known congenital heart disease.
J Pediatr. 1993;122(5 Pt 1):821-3. 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

Goldberg-Stern H, Strawsburg RH, Patterson B, Hickey F, Bare M, Gadoth N, Degrauw TJ.
Seizure frequency and characteristics in children with Down syndrome.
Brain Dev. 2001;23(6):375-8. PubMed abstract

Grammatikopoulou MG, Manai A, Tsigga M, Tsiligiroglou-Fachantidou A, Galli-Tsinopoulou A, Zakas A.
Nutrient intake and anthropometry in children and adolescents with Down syndrome--a preliminary study.
Dev Neurorehabil. 2008;11(4):260-7. 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

Leonard S, Bower C, Petterson B, Leonard H.
Survival of infants born with Down's syndrome: 1980-96.
Paediatr Perinat Epidemiol. 2000;14(2):163-71. PubMed abstract / Full Text
There has been a considerable improvement in survival of infants born with Down’s syndrome in Western Australia. This improvement is similar to findings in recent international studies. The difference in survival between Aboriginal and non-Aboriginal children is particularly disturbing. These findings are useful for both clinicians and families who need to plan for the long-term care of these children.

Mercer ES, Broecker B, Smith EA, Kirsch AJ, Scherz HC, A Massad C.
Urological manifestations of Down syndrome.
J Urol. 2004;171(3):1250-3. 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

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

Quinlivan R, Roper H, Davie M, Shaw NJ, McDonagh J, Bushby K.
Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention.
Neuromuscul Disord. 2005;15(1):72-9. PubMed abstract

Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK.
Update of newborn screening and therapy for congenital hypothyroidism.
Pediatrics. 2006;117(6):2290-303. PubMed abstract

Stafstrom CE, Konkol RJ.
Infantile spasms in children with Down syndrome.
Dev Med Child Neurol. 1994;36(7):576-85. 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

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