Down Syndrome

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  • Down syndrome (DS) is a congenital condition associated with intellectual disability and an increased risk of multisystem medical problems.
  • System(s) affected: neurologic (100%), cardiac (40–50%), GI (8–12%)
  • Synonym(s): trisomy 21

Pediatric Considerations
Murmur may not be present at birth. Delay in recognition of heart condition may lead to irreversible pulmonary hypertension.

Geriatric Considerations
  • Life expectancy has increased to ~60 years.
  • Age-related health issues occur at earlier age than in the general population.
  • Communication difficulties may interfere with prompt recognition of some medical issues.
Pregnancy Considerations
  • American College of Obstetricians and Gynecologists (ACOG) recommends all pregnant women be offered traditional prenatal screening and diagnostic testing for DS.
    • Maternal prenatal screening may be performed in the 1st or 2nd trimester.
    • Prenatal diagnostic tests include chorionic villus sampling or amniocentesis.
  • ACOG and the Society for Maternal-Fetal Medicine (SMFM) acknowledge that any women may choose noninvasive prenatal screening (NIPS), although conventional screening tests might be more appropriate. American College of Medical Genetics and Genomics (ACMG) recommends all women be offered NIPS (1,2).
  • Most, but not all, men with DS are believed to be infertile.
  • Most women with DS are subfertile but can conceive children with and without DS.


In the United States, 1/792 live births, ~5,300 births per year (3)

~206,000 persons in the United States (4)

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
  • Chance of having an infant with DS increases with mother’s age.
  • Relatively more infants with DS are born to younger mothers because younger women are more likely to become pregnant.
  • Prenatal diagnosis of DS is more common in older women, and a high percentage of such pregnancies are electively terminated.

General Prevention

  • No prevention for nondisjunction trisomy 21
  • 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%); autism (<6%)
    • Seizures (8%); typically occurring <1 year of age 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), oppositional defiant disorder (ODD), and autism spectrum disorder increased frequency in children.
    • Generalized depression and anxiety with increased frequency in young adults/adults
  • Sensory
    • Hearing loss (75%): mostly conductive due to high frequency of asymptomatic middle ear effusion; otitis media (50–70%)
    • Visual impairment (60%): mostly strabismus (refractive errors, 15%), nystagmus, cataracts (15%)
  • Dermatologic
    • Xerosis, eczema, palmoplantar hyperkeratosis, atopic or seborrheic dermatitis, onychomycosis, syringomas, furunculosis/folliculitis

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