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Down Syndrome

Basics

Description

  • Down syndrome (DS) = congenital trisomy 21 associated with intellectual disability and multisystem medical complications

  • Pediatric: requires multidisciplinary evaluation

  • Geriatric: life expectancy ~60 years

  • Pregnancy: All women may opt for noninvasive prenatal screening (NIPS) per ACOG, SMFM, and ACMG

Epidemiology

  • Incidence: 1 in 772 live births (~5,100/year in U.S.)

  • Prevalence: ~217,000 individuals in the U.S.

Etiology & Pathophysiology

  • Trisomy 21 (95%): maternal meiotic nondisjunction

  • Translocation (3–4%): chromosome 21q material on chromosomes 13, 14, or 21

  • Mosaicism (1–2%): some cells normal β†’ milder phenotype

  • Genetics:

    • Most cases sporadic

    • Recurrence risk:

      • 1% after nondisjunction

      • 10–15% for mothers/sisters with balanced translocation

      • 100% if parental 21;21 translocation

Risk Factors

  • Maternal age ↑

  • Occurs across all ethnicities, though live birth rates vary due to elective terminations

Prevention

  • Preimplantation genetic testing with IVF

  • Prenatal diagnosis (CVS/amniocentesis) with possible elective termination

  • Adoption as an option

Commonly Associated Conditions

Cardiac

  • Congenital heart defects (40–50%)

GI / Growth

  • Feeding issues, GERD, constipation, celiac disease (~5%)

Pulmonary

  • Tracheal anomalies, pulmonary hypertension, OSA (50–75%)

Genitourinary

  • Cryptorchidism, hypospadias

Hematologic/Oncologic

  • Transient myeloproliferative disorder (~10%)

  • Risk of AMKL, ALL (0.5–1%)

  • ↓ solid tumor risk; ↑ germ cell/testicular tumors

Endocrine

  • Hypothyroidism (13–63%), diabetes

Skeletal

  • Atlantoaxial instability (15%), scoliosis, short stature

Immune/Rheumatologic

  • ↑ infections, ↑ autoimmune (Hashimoto, alopecia, celiac)

Neurologic

  • Moderate intellectual disability, hypotonia, seizures (8%)

  • Alzheimer’s signs by age 40 in β‰₯40%

  • Rare: Down syndrome regression disorder

Psychiatric

  • ↑ ADHD, OCD, autism, anxiety, depression

Sensory

  • Hearing loss (75%), otitis media, visual impairment (60%)

Dermatologic

  • Eczema, xerosis, seborrheic dermatitis, onychomycosis

Diagnosis

History

  • 85% of mothers learn diagnosis postnatally, though this is changing with NIPS

Physical Exam

  • Brachycephaly (100%), hypotonia (80%)

  • Low-set ears, upslanting palpebral fissures (90%)

  • Epicanthic folds, Brushfield spots

  • Short neck, single palmar crease

  • Toe gap, clinodactyly, brachydactyly

Diagnostic Tests

Prenatal Screening

  • 1st Trimester: Combined screen (Ξ²-hCG, PAPP-A, nuchal translucency)

  • 2nd Trimester: Quad screen (AFP, Ξ²-hCG, estriol, inhibin A)

  • NIPS (cfDNA): from ~10 weeks

Prenatal Diagnosis

  • CVS: ~99% accurate; ~1% miscarriage

  • Amniocentesis: ~99% accurate; ~0.25% risk

Postnatal Testing

  • FISH for rapid screen; confirm with karyotyping

  • Parental karyotype if translocation

  • Newborn workup:

    • Echocardiogram

    • CBC with differential

    • TSH, audiogram

    • Ophthalmology exam, swallowing study, car seat test

Special Considerations

  • Use DS-specific growth charts

  • Use compassionate, private counseling if diagnosed postnatally

Treatment

Referrals

  • Lactation, PT/OT/ST, cardiologist

Surgery

  • Correct congenital anomalies if present

CAM

  • No supplements supported

  • Avoid craniosacral therapy (due to atlantoaxial instability)

Admission & Nursing

  • If adoption planned, refer to NDSAN

Ongoing Care

Follow-Up

AAP Recommendations:

  • Vision: baseline by 6 mo, then regularly

  • Hearing: ABR/OAE at birth β†’ audiogram every 6 months (up to age 3), then annually

  • TSH: newborn, 6 mo, 12 mo, then annually

  • Celiac screen if symptomatic

  • Cervical spine X-rays if symptomatic, age 3–5+

  • CBC annually for iron-deficiency anemia

  • Repeat ECHO in teens if murmur or fatigue

  • Polysomnography (age 3–5) for all due to OSA prevalence

Diet

  • No specific diet, but lower caloric needs

  • Monitor and manage obesity

Patient Education

Prognosis

  • 99% of young adults/adults with DS report happiness

  • Life expectancy β‰ˆ 60 years

References

  1. Bull MJ, et al. Pediatrics. 2022

  2. Rose NC, et al. Obstet Gynecol. 2020

  3. Dungan JS, et al. Genet Med. 2023

  4. Zemel BS, et al. Pediatrics. 2015

  5. Tsou AY, et al. JAMA. 2020
    Additional: Antonarakis SE, et al. Nat Rev Dis Primers. 2020

See Also

  • Algorithm: Intellectual Disability

ICD-10 Codes

  • Q90.0 – Trisomy 21, nonmosaicism

  • Q90.1 – Trisomy 21, mosaicism

  • Q90 – Down syndrome (unspecified)

Clinical Pearls

  • 99% of DS individuals are happy with their lives

  • Virtual DS specialty clinics (e.g., DSC2U) improve care

  • Multidisciplinary, lifespan approach is essential