Down Syndrome (Trisomy 21)
The syndrome characterized by an abnormal number of chromosomes in this child is Down syndrome, caused by trisomy 21—the presence of an extra copy of chromosome 21. 1
Genetic Basis
Down syndrome results from the presence of an extra copy of chromosome 21, occurring through three mechanisms 1:
Free trisomy 21 (~95% of cases): Results from sporadic nondisjunction during parental meiosis
- Maternal origin in 95% of cases
- 77% occur during Meiosis I
- Risk increases with advancing maternal age
Robertsonian translocation involving chromosome 21: Can be inherited when a parent carries the translocation
Reciprocal translocation involving chromosome 21: Less common variant
Clinical Features
Down syndrome is one of the most common genetic causes of moderate to severe intellectual disability 1. The condition presents with a characteristic constellation of features:
Universal Features
- Hypotonia (present in virtually all individuals)
- Intellectual disability ranging from moderate to severe 1
Dysmorphic Features 1
- Upslanting palpebral fissures
- Epicanthal folds
- Flat nasal bridge
- Brushfield spots of the iris
- Shortened, incurving fifth finger
- Transverse palmar crease
Major Organ System Involvement
- Cardiac: Congenital heart disease in 40% of cases 1
- Gastrointestinal: 5% have anomalies such as duodenal atresia or Hirschsprung disease 1
- Hematologic: Childhood leukemia risk increased up to 20-fold over general population 1
Long-term Complications
Adults with Down syndrome experience neuronal degeneration identical to Alzheimer disease 2. By age 40 years, all adults with Down syndrome exhibit neuropathologic defects meeting criteria for Alzheimer disease, though clinical dementia is not inevitable 2. At least 50% of adults aged 60 years and older will have clinical evidence of dementia 2.
Prognosis
Individuals with Down syndrome without congenital heart disease can live beyond 60 years of age 1. The survival rate has increased dramatically from less than 50% during the mid-1990s to 95% in the early 2000s, with median life expectancy now reaching 60 years 3.
Diagnostic Confirmation
The definitive diagnostic test for Down syndrome is karyotyping of fetal cells, usually obtained by chorionic villus sampling (CVS) or amniocentesis 1. Newer diagnostic technologies using fluorescence in situ hybridization (FISH) or quantitative fluorescent polymerase chain reaction may also be employed 1.
Important Caveat
Prenatal screening tests using maternal serum markers and nuchal translucency measurements are screening tests, not diagnostic tests—they identify pregnancies at sufficient risk to warrant genetic counseling and offer of diagnostic testing 1, 4.