U01.01.064 Autosomal trisomies

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Learning Objective:

By the end of this session, the learner will be able to: Describe the genetics, clinical features, prenatal screening findings, and complications of common autosomal trisomies (Down, Edwards, and Patau syndromes).

Autosomal trisomies result from meiotic nondisjunction, producing gametes with an extra chromosome. Most common: Down syndrome (Trisomy 21) > Edwards (18) > Patau (13). Autosomal monosomies are incompatible with life because of the complete loss of essential genes.

Down Syndrome (Trisomy 21)

Feature	Description
Genetics	Extra copy of chromosome 21 due to meiotic nondisjunction (95%), Robertsonian translocation (4%), or mitotic error (1%).
Risk factor	Advanced maternal age — nondisjunction risk rises sharply after age 35.
Clinical findings	Intellectual disability, flat facies, epicanthal folds, single palmar crease, incurved 5th finger, gap between 1st and 2nd toes, congenital heart disease (AVSD), duodenal atresia, Hirschsprung disease, and Brushfield spots.
Associations	Early-onset Alzheimer’s disease, ↑ risk of AML/ALL, and umbilical hernia.
Screening	↑ hCG, ↑ inhibin A, ↑ nuchal translucency, ↓ PAPP-A.
Mnemonic – 6 As	Atlantoaxial instability, Advanced maternal age, Atresia (duodenal), AV septal defect, Alzheimer’s (early), AML/ALL.
Age mnemonic	Drinking age = 21.

Edwards Syndrome (Trisomy 18) 👶

Feature	Description
Genetics	Nondisjunction leading to an extra chromosome 18.
Clinical findings	PRINCE Edward: Prominent occiput, Rocker-bottom feet, Intellectual disability, Nondisjunction, Clenched fists (overlapping fingers), low-set Ears. Also: micrognathia, congenital heart defects, omphalocele, myelomeningocele.
Screening	↓ β-hCG, ↓ PAPP-A (first trimester), ↓ hCG, ↓ estriol, ↓ AFP (quad test).
Prognosis	Death usually occurs by age 1.
Age mnemonic	Election age = 18.

Patau Syndrome (Trisomy 13) ❤️

Feature	Description
Genetics	Nondisjunction or translocation causes an extra chromosome 13.
Clinical findings	Severe intellectual disability, microphthalmia, microcephaly, cleft lip/palate, polydactyly, holoprosencephaly, rocker-bottom feet, cutis aplasia, congenital heart defects, polycystic kidney disease, and omphalocele.
Screening	↓ β-hCG, ↓ PAPP-A; no significant changes in quad test markers.
Prognosis	Death usually occurs by age 1.
Age mnemonic	Puberty = 13.