Down Syndrome (Trisomy 21)

Basics

Description

Syndrome first described by John Langdon Down in 1866 consisting of multiple abnormalities, including hypotonia, flat facies, upslanting palpebral fissures, and small ears; also called “trisomy 21”; other abnormalities include the following:

  • Congenital heart disease (40–50%; most not symptomatic as a newborn)
    • Atrioventricular (AV) canal (60% of those with congenital heart disease)
    • Ventricular septal defect (VSD)
    • Patent ductus arteriosus (PDA)
    • Atrial septal defect (ASD)
    • Aberrant subclavian artery
    • Tetralogy of Fallot
  • Hearing loss (66–75%): sensorineural and conductive
  • Strabismus (33–45%)
  • Nystagmus (15–35%)
  • Fine lens opacities (by slit-lamp examination 59%), cataracts (1–15%)
  • Refractive errors (50%)
  • Nasolacrimal duct stenosis
  • Delayed tooth eruption
  • Tracheoesophageal fistula
  • Airway anomalies, including tracheo- and laryngomalacia
  • Obstructive sleep apnea (30–60%)
  • Gastrointestinal atresia (12%)
  • Celiac disease
  • Meckel diverticulum
  • Hirschsprung disease (<1%)
  • Imperforate anus
  • Renal malformations
  • Hypospadias (5%)
  • Cryptorchidism (5–50%)
  • Testicular microlithiasis
  • Thyroid disease (15–33%): hypothyroidism, hyperthyroidism
  • Transient myeloproliferative disorder (3–10%), neonatal (leukemoid reaction)
  • Transient neonatal polycythemia, neutrophilia, thrombocytopenia
  • Leukemia (<1%; 10 to 20 times greater risk than in general population, acute lymphoblastic and myeloid leukemias)
  • Decreased T and B lymphocytes
  • Testicular germ cell tumors
  • Infertility, especially in males
  • Obesity
  • Alopecia areata (10–15%)
  • Seizures (5–10%), usually myoclonic
  • Alzheimer disease (Nearly all age >40 years show neuropathologic signs.)
  • Mild to moderate mental retardation (IQ range 25 to 70)
  • Dry, hyperkeratotic skin (75%)

Epidemiology

  • Population prevalence: 8.3/10,000 population
  • 14/10,000 live births
  • Male > female (1.3:1)
  • Best recognized and most frequent chromosomal syndrome of humans
  • One of the three most common autosomal trisomies in humans (Others are trisomies 18 and 13.)
  • Most common autosomal chromosomal abnormality causing mental retardation
  • >50% of trisomy 21 fetuses are spontaneously aborted in early pregnancy.

Incidence

1/600 to 1/800 live births, although incidence varies with maternal age:

  • 1/1,500 for maternal ages 15 to 29 years
  • 1/800 for maternal ages 30 to 34 years
  • 1/270 for maternal ages 35 to 39 years
  • 1/100 for maternal ages 40 to 49 years

Risk Factors

Genetics

  • Approximately 90% of cases are the result of chromosomal nondisjunction (failure to segregate during meiosis) in the maternal DNA.
  • <5% of cases are the result of paternal nondisjunction.
  • 3–4% of cases are the result of translocations; mostly chromosomes 21 and 14 [t(14q21q)]; rarely between chromosome 21 and 13 or 15; 75% of translocations are sporadic de novo events; the others result from balanced translocations in one parent.
  • Of live births, 1–2% are mosaic (nondisjunction occurs after conception; two cell lines are present); generally less severely affected

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