Down Syndrome

Key Features

Essentials of Diagnosis

• Typical craniofacial features (flat occiput, epicanthal folds, large tongue)

• Intellectual disability

• Congenital heart disease (eg, atrioventricular canal defects) in 50% of patients

• Three copies of chromosome 21 (trisomy 21) or a chromosome rearrangement that results in three copies of a region of the long arm of chromosome 21

General Considerations

• Maternal age is risk factor of increasing the chance of having a child with Down syndrome

  • Risk increases exponentially with the age of the mother at conception

  • Risk rises markedly after age 35

  • By age 45 years, the odds of having an affected child are as high as 1 in 40

• The risk of other conditions associated with trisomy also increases because of the predisposition of older oocytes to nondisjunction during meiosis

• Increased paternal age is not associated with risk of trisomy

Demographics

• Nearly 0.5% of all human conceptions are trisomic for chromosome 21

• Because of increased fetal mortality, birth incidence of Down syndrome is 1 per 700 but varies from 1 per 1000 in young mothers to more than three times as frequent in women of advanced maternal age

Clinical Findings

• Typical craniofacial features

• Hypotonia

• Single palmar crease

• Duodenal atresia

• Congenital heart disease

• Hematologic malignancy

• An Alzheimer-like dementia usually becomes evident in the fourth or fifth decade

Diagnosis

• Cytogenomic analysis

• Prenatal detection

  • "Multiple marker screening" (screening maternal serum for alpha-fetoprotein and other biomarkers) in the first trimester or early in the second trimester

  • Ultrasonography can visualize increased nuchal thickness and underdevelopment of the nasal bone

  • Assaying fetal DNA that is circulating in maternal blood can diagnose Down syndrome with high sensitivity and specificity

Treatment

• Duodenal atresia should be treated surgically

• Congenital heart disease should be treated as in any other patient

• Any leukemia typically responds to reduced-dose chemotherapy

• No medical treatment has been proven to affect the neurodevelopmental or the neurodegenerative aspects

• Supplementation with antioxidants has shown no benefit

Outcome

Complications

• Atlanto-axial instability

• Celiac disease

• Frequent infections due to immune deficiency

• Hypothyroidism

Prognosis

• Patients who survive childhood and in whom dementia develops have a reduced life expectancy; on average, they live to about age 55 years

• The intestinal and cardiac anomalies usually respond to surgery

• A transient neonatal leukemia generally responds to conservative management

• If relapse of leukemia occurs, outcome is poor

When to Refer

• For comprehensive evaluation of infants to investigate congenital heart disease, hematologic malignancy, and duodenal atresia

• For genetic counseling of the parents

• For signs of dementia ...