Down Syndrome / Trisomy 21: Clinical Findings and Prenatal Considerations

WHAT IS IT?

  • Down syndrome is the most common chromosomal cause of intellectual disability
  • May affect almost every organ system but the following findings are particularly common and may be identified on prenatal sonogram:
    • Increased nuchal translucency (first trimester) and/or nuchal fold (second trimester) or cystic hygroma
    • Congenital heart disease (50%), particularly AV canal defects
    • Duodenal atresia (double bubble sign) usually identified in 3rd trimester
    • Prenatal ultrasound markers include: short femurs, echogenic intracardiac foci, dilated renal pelviectasis, mild ventriculomegaly
  • Other findings may not be apparent until postnatal life:
    • Dysmorphic features: epicanthal folds, single palmar crease, low set ears
    • Decreased muscle tone
    • Intellectual disability: usually in the mild (IQ ~70) to moderate range (IQ ~50)
      • Most individuals with Down syndrome can participate in numerous group and individuals activities, but may need some level of supervision throughout their lives
      • Individualized education programs can help children with Down syndrome reach their potential
      • Special education services at school can range from inclusion in the typical classroom with extra help to small group instruction
    • Hearing loss (up to 75%)
    • Sleep apnea (50-75%)
    • Eye disease, such as cataracts (50-70%)
    • Endocrine disease: thyroid, diabetes
    • Hirschsprung disease
    • Leukemia is slightly increased in this population, typically requiring lower doses of chemotherapy treatments
    • Plaques are frequently seen in older adults with Down syndrome (50+ years) but their presence does not mean that Alzheimer’s disease will necessarily develop – other treatable causes of decline are investigated first

CAUSE:

Down syndrome (DS) is a condition caused by the presence of an extra chromosome (#21) at the time of conception. In 90% of cases, it is the result of nondisjunction during meiosis (Trisomy 21), which is usually a sporadic occurrence. In 4-5% of DS affected individuals a chromosomal imbalance is the cause, inherited from a parent who has a balanced karyotype (i.e. Robertsonian translocation). A small proportion of affected individuals, < 1%, are diagnosed with mosaic DS.

KEY POINTS:

  • ACOG requires all women be offered prenatal screening (biochemical/cfDNA) or invasive testing (amniocentesis;CVS) to detect an increased risk for DS, or to diagnosis it, respectively
  • Children with Down syndrome are more similar to other children than they are different
  • Overall, this condition is present in approximately 1 in 800 live births. Risk increases with maternal age
    • At maternal age 25, the risk is 1/1250
    • At maternal age 35, the risk is 1/365
    • At maternal age 40, the risk is 1/110
    • At maternal age 45, the risk is 1/32
  • If there is a family history or previous DS pregnancy, refer for genetic counseling
  • Data is limited on obstetrical management of an ongoing pregnancy with trisomy 21
    • Increased risk of fetal loss (5.9%), growth restriction (17.5%) and anomalies (75.0%)
    • Non-reassuring fetal surveillance (35.9%) appears to be associated with placental insufficiency and not necessarily related to structural anomalies
    • Data suggests a role for antepartum surveillance

Note: ACMG provides healthcare professionals with open access ‘ACT Sheets’ to guide next steps following a positive NIPS report for trisomy 21 (see ‘Learn More – Primary Sources’ below) 


Learn More – Primary Sources:

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

ACMG: Noninvasive Prenatal Screening via Cell-Free DNA [Trisomy 21: Positive Cell Free DNA Screen]

Antepartum management and obstetric outcomes among pregnancies with Down syndrome from diagnosis to delivery

CDC: Facts about Down syndrome

lettercase.org: Understanding a Down syndrome Diagnosis

Practice Guidelines for Communicating a Prenatal or Postnatal Diagnosis of Down Syndrome: Recommendations of the National Society of Genetic Counselors

Locate a Genetic Counselor or Genetics Services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC