Down Syndrome



  • Down syndrome (DS) is a congenital condition associated with intellectual disability and an increased chance of multisystem medical problems.
  • Synonym: trisomy 21

Pediatric Considerations
Murmur may not be present at birth.

Geriatric Considerations
Life expectancy has increased to ~60 years.

Pregnancy Considerations

  • The American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM) and the American College of Medical Genetics and Genomics (ACMG) recommends all women be offered traditional prenatal screening and diagnostic testing for DS.
  • ACOG and the SMFM acknowledge that any women may choose noninvasive prenatal screening (NIPS). ACMG recommends all women be offered NIPS (1),(2).


In the United States, 1/792 live births, ~5,300 births per year

~212,000 persons in the United States (3)

Etiology and Pathophysiology

  • Etiology: presence of all or part of an extra chromosome 21
  • Trisomy 21: 95% of DS, an extra chromosome 21 is found in all cells due to nondisjunction, usually in maternal meiosis.
  • Translocation DS: 3–4% of DS, extra chromosome 21q material is translocated to another chromosome (usually 13, 14, or 21); ~25% have parental origin.
  • Mosaic trisomy 21: 1–2% of DS, manifestations may be milder.


  • Online Mendelian Inheritance in Man (OMIM) 190685
  • Inheritance: most commonly sporadic nondisjunction resulting in trisomy 21
  • Chance of having another child with DS is
    • 1% (or age risk, whichever is greater) after conceiving a pregnancy with nondisjunction trisomy 21
    • 10–15% for mothers/sisters and 3–5% for fathers/brothers who carry balanced translocation with chromosome 21
    • 100% if the parental balanced translocation is 21;21 (45,t[21;21])
    • Unclear after child with mosaic DS but ~1%

Risk Factors

  • DS believed to occur in all races and ethnicities with equal frequency, although live birth prevalence may differ based on different elective termination rates
  • Chance of having an infant with DS increases with mother’s age.

General Prevention

Preimplantation diagnosis with in vitro fertilization (IVF), prenatal diagnosis followed by termination, and adoption are current options for expectant parents who do not wish to raise a child with DS.

Commonly Associated Conditions

  • Cardiac
    • Congenital heart defects (40–50%)
  • GI/growth
    • Feeding problems are common in infancy.
    • Structural defects (~12%)
    • Gastroesophageal reflux
    • Constipation
    • Celiac disease (~5%)
  • Pulmonary
    • Tracheal stenosis/tracheoesophageal fistula
    • Pulmonary hypertension
    • Obstructive sleep apnea (50–75%)
  • Genitourinary
    • Cryptorchidism, hypospadias
  • Hematologic/neoplastic
    • Transient myeloproliferative disorder (~10%): generally resolves spontaneously; can be preleukemic (acute megakaryoblastic leukemia [AMKL]) in 20–30%
    • Leukemia (AMKL or acute lymphoblastic leukemia [ALL]) in 0.5–1%
    • Decreased risk of most solid tumors; increased risk of germ cell tumors/testicular cancer
  • Endocrine
    • Hypothyroidism: congenital or acquired (13–63%)
    • Diabetes
  • Skeletal
    • Atlantoaxial instability (15%): ~2% symptomatic
    • Short stature is common.
    • Scoliosis (Some cases have adult onset.)
    • Hip problems (1–4%)
  • Immune/rheumatologic
    • Abnormal immune function with increased rate of respiratory infections
    • Increased risk of autoimmune disorders, including Hashimoto thyroiditis, celiac disease, and alopecia
  • Neurologic
    • Intellectual ability ranging from mild to severe disability. Average is moderate intellectual disability.
    • Autism spectrum disorder (<18%)
    • Hypotonia
    • Seizures (8%); typically occurring <1 year of age (infantile spasms) or >30 years of age
    • Alzheimer disease: At least 40% at age 40 years develop signs of dementia; percentage increases with age.
  • Psychiatric
    • Attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and autism spectrum disorder increased frequency in children.
    • Generalized depression and anxiety with increased frequency in young adults/adults
    • Down syndrome disintegrative disorder is a very rare clinical regression syndrome that can occur in adolescents or young adults (4).
  • Sensory
    • Hearing loss (75%): mostly conductive due to high frequency of asymptomatic middle ear effusion; otitis media (50–70%)
    • Visual impairment (60%): strabismus (refractive errors, 15%), myopia, hyperopia, nystagmus, cataracts (15%)
  • Dermatologic
    • Xerosis, eczema, palmoplantar hyperkeratosis, atopic or seborrheic dermatitis, onychomycosis, syringomas, furunculosis/folliculitis, hidradenitis suppurativa

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