Pathophysiology

congenital mental retardation caused by trisomy 21 (an extra chromosome 21)

Signs and Symptoms

1) moderate mental retardation progressing to severe mental retardation (IQ of 30 in adulthood) 2) characteristic mongoloid facies – flat nasal bridge, epicanthic folds, oblique palpebral fissures 3) short stature and obesity 4) spade-like hands with simian creases 5) speckled irises (Brushfield’s spots) 6) hypotonia 7) congenital heart defects – VSD, ASD, tetralogy of Fallot, and patent ductus arteriosus

Associated Conditions

1) increased incidence with advanced maternal age (1/30 live births at age 45 years) and previous child with Down syndrome 2) increased incidence of leukemia (especiallly ALL), Alzheimer’s disease (25-50%) by age 35 years), Hirschsprung’s disease, imperforate anus, duodenal stenosis, and atresia

Histology/Gross Pathology

1) senile plaques 2) neurofibrillary tangles 3) deposition of beta-amyloid protein in the brain

Biochemistry

mechanisms for production of trisomy 21 – nondisjunction during first meiotic division of gametogenesis (94% of cases), translocation of an extra long arm of chromosome 21 (5%), and mosaicism (1%)

Inheritance/Epidemiology

most common cause of congenital mental retardation

Treatment

surgery for congenital heart defects

Tips for USMLE

1) if Brushfield spots are mentioned, think Down’s 2) if question mentions a Down’s child, look for development of leukemia (ALL) or Alzheimer’s in the case scenario 3) if question mentions a Down’s child, look for the presence of congenital heart defects