U01.01.064 Autosomal trisomies

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Learning Objectives

  • Identify the clinical features of Down, Edwards, and Patau syndromes.
  • Explain the mechanism of meiotic nondisjunction and the impact of maternal age.
  • Interpret first and second-trimester screening markers for autosomal trisomies.
  • Recognize high-yield associations, such as early-onset Alzheimer’s and hematologic malignancies.

1. Mechanism: Nondisjunction

Most autosomal trisomies result from a failure of chromosomes to separate properly during meiosis.

  • Meiosis I Nondisjunction: Results in gametes that are either n+1 or n-1. This is the most common cause of Down Syndrome, especially with advanced maternal age.
  • Meiosis II Nondisjunction: Results in two normal gametes (n), one n+1, and one n-1.

2. Clinical Comparison of Trisomies

Syndrome Findings (High-Yield) Mnemonics/Notes
Down Syndrome (21) Flat facies, epicanthal folds, single palmar crease, duodenal atresia, AV septal defects. The 6 As: Atlantoaxial instability, Age, Atresia, AVSD, Alzheimer, AML/ALL.
Edwards Syndrome (18) Prominent occiput, rocker-bottom feet, clenched fists (overlapping fingers), micrognathia. PRINCE Edward: Prominent occiput, Rocker-bottom, Intellectual disability, Nondisjunction, Clenched fists, Ears (low-set).
Patau Syndrome (13) Cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia. Puberty at 13: Midline defects (clefting, holoprosencephaly).

3. Prenatal Screening Markers

Screening depends on the trimester and the specific trisomy being evaluated.

First Trimester (β-hCG & PAPP-A)

  • Down (21): ↑ hCG, ↓ PAPP-A. (Markers are “HI” up: HCG and Inhibin).
  • Edwards (18) & Patau (13): ↓ All markers.

Second Trimester (Quad Screen)

Trisomy hCG Inhibin A Estriol AFP
21 (Down) ↑ ↑ ↓ ↓
18 (Edwards) ↓ ↓ (or —) ↓ ↓

4. High-Yield Associations

  • Alzheimer Disease: Down syndrome patients have a highly increased risk of early-onset Alzheimer’s because Chromosome 21 codes for amyloid precursor protein (APP).
  • Hematologic Malignancies: Down syndrome is associated with AML (specifically M7 subtype, < 5 years old) and ALL (> 5 years old).
  • Nuchal Translucency: Increased in the first-trimester ultrasound for Down syndrome.

 

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