Trisomy 21 (Down Syndrome)

Definition

Epidemiology

• Most common trisomy compatible with live birth (others include Edwards and Patau Syndromes)
• Incidence between 1/700 to 1/1000, parental age-related
• High infant mortality (prevalence in population is 1/3000)
• 93%:  Complete extra copy of chromosome 21 in all cells, as a result of meitotic disjunction (80-90% of which are from maternal nondisjuntion).
•  5%:  Extra chromosome 21 from a translocation, often a balanced 14:22 translocation
•  3%:  Mosaics resulting from meitotic nondisjunction.

Risk Factors

• Maternal age
• Parental carrier of translocation

Prenatal Testing

• Triple screen (alpha-fetal protein decreased, estriol decreased, beta-HCG increased)
• If positive, amniocentesis or chorionic villus sampling may be indicated

Clinical Features

• Hypotonia ("you can't have Down Syndrome without hypotonia")
• Mental retardation
• Short stature
• Prematurity
• Lower birth weights
• Brachycephaly
• Macroglossia
• Small mandible and maxilla
• Excess nuchal skin
• Epicanthal folds
• Flat, depressed nasal bridge
• Atlantoaxial instability
• Velvety, loos adhering mottled skin in infancy; coarse skin in adolescence
• Palpebral fissures slant upwards
• Brushfield spots
• Single palmar crease
• Posterioly rotated ears
• Upturned nose
• Flattened occiput
• Short, broad hands
• Clinodactyly of the fifth finger
• Gap between the first and second toes

Diagnosis

Complications

• Congenital Heart Disease
• Usually endocardial cushion defects, followed by ASD and VSD
• Surgical repair with increase survival
• Gastrointestinal Malformation
• Duodenal atresis or stenosis
• Esophageal atresia
• Anal atresia
• Megacolon (Hirschprung's)
• Hearing Loss
• Conductive hearing loss
• May be secondary to serous otitis media
• Ophthalmic Complications
• Cataracts, nystagmus, strabismus present early
• Myopia in preschool
• Joint Instability
• Especially increased risk of atlantoaxial (C1-C2) subluxation
• Oncology
• 10-30 fold increased risk of leukemia

Prognosis

• 30 die within the first one year, and 50% die within 5 years
• 10 year survival with heart disease is 75%; without is 95%
• After age 10, average life span is 55 years