STEPTRACKERGENETICS + OBSTETRICS | CHROMOSOMAL DISORDERS | HIGH-YIELD REVIEW

Autosomal Trisomies

Three extra-chromosome syndromes that survive to birth — their faces, hearts and prenatal screening signatures.

FOCUS ON
Down (21) > Edwards (18) > Patau (13) in frequency ("drinking age 21, election age 18, puberty 13"). ~95% of Down = meiotic nondisjunction (↑ maternal age), ~4% Robertsonian translocation (recurs, not age-linked), ~1% mosaic. Quad screen: Down = ↓ AFP, ↑ β-hCG, ↓ estriol, ↑ inhibin A; Edwards = all ↓ (inhibin normal/↓); Patau shows on first-trimester ↓ PAPP-A, ↓ hCG.
SYNDROME
CAUSE
FEATURES
SCREEN · CLUE
Down syndrome
trisomy 21
Nondisjunction in maternal meiosis I (most); Robertsonian 14;21 or 21;21; mosaicism
Flat facies, epicanthal folds, upslanting fissures, single palmar crease, sandal gap, Brushfield spots, ID, hypotonia
↑ Nuchal translucency, hypoplastic nasal bone
Down — heart & gut
Endocardial cushion defects
AV septal defect (most), VSD, ASD · duodenal atresia (double bubble), Hirschsprung
Echo all newborns with Down
Down — later risks
Extra APP gene (ch 21), immune and endocrine effects
Early-onset Alzheimer (by 40s), ALL and AML (M7 megakaryoblastic, transient myeloproliferative disorder), hypothyroidism, atlantoaxial instability, celiac
↓ Risk of many solid tumors
Edwards syndrome
trisomy 18
Nondisjunction
Severe ID, rocker-bottom feet, clenched fists with overlapping fingers, micrognathia, prominent occiput, low-set ears, VSD
Death usually within 1 year
Patau syndrome
trisomy 13
Nondisjunction
Severe ID, holoprosencephaly, cleft lip/palate, polydactyly, microphthalmia, cutis aplasia, omphalocele, rocker-bottom feet
Death usually within 1 year
Nondisjunction
Chromosomes fail to separate in meiosis I (homologs) or II (sister chromatids)
Trisomy or monosomy in the conceptus
Risk rises with maternal age
Robertsonian translocation
Fusion of long arms of two acrocentric chromosomes (13, 14, 15, 21, 22); balanced carriers are normal
Unbalanced gametes → translocation Down, recurrent miscarriage
Karyotype parents; recurrence high (esp. 21;21 → 100%)
Mosaicism
Postzygotic nondisjunction → two cell lines
Milder phenotype
Not maternal-age related
Cell-free fetal DNA
Placental DNA in maternal blood sequenced from ~10 weeks
Most sensitive screening for trisomies
Screening only — confirm with CVS or amniocentesis
Monosomies
Autosomal monosomies are lethal
Only 45,X survives (Turner, 5.08)
Common cause of first-trimester loss

Picture it — how extra chromosomes happen

n+1n+1n−1n−1Meiosis I error
Meiosis I nondisjunctionHomologs fail to separate → all four gametes abnormal (two n+1, two n−1).
n+1n−1nnMeiosis II error
Meiosis II nondisjunctionSister chromatids fail to separate → one n+1, one n−1, two normal.
14 + 21fused (short arms lost)
Robertsonian translocationLong arms of two acrocentric chromosomes fuse; carriers are healthy but can make unbalanced gametes.

Schematic diagrams, not to scale.

Mechanism — nondisjunction

Meiosis I errorHomologs don't separate
→
Two gametes n+1, two n−1
Meiosis II errorSister chromatids don't separate
→
One n+1, one n−1, two normal

Maternal meiosis I is the usual source in Down syndrome; oocytes sit in prophase I for decades, which is why age matters.

Second-trimester quad screen

MARKER
DOWN
EDWARDS
NTD
AFP
↓
↓
↑
β-hCG
↑
↓
—
Estriol
↓
↓
—
Inhibin A
↑
↓ / —
—

How it's tested

COMMON CONFUSION"HI" is high in Down (hCG, Inhibin); everything is low in Edwards. Neural tube defects raise AFP.
THE TRAPA young mother with a second Down baby → check parental karyotype for a Robertsonian translocation; recurrence risk is far above the age-based figure.
YOUR APPROACHFacial/limb clue → trisomy number → mechanism → recurrence counseling and associated heart/gut defects.

If you see… think…

Newborn with double-bubble X-ray and flat face → Down (duodenal atresia)
Down syndrome heart defect → AV septal (endocardial cushion) defect
Dementia in a 45-year-old with Down → Alzheimer (extra APP)
Rocker-bottom feet, clenched overlapping fingers → Edwards (18)
Holoprosencephaly, cleft lip, polydactyly → Patau (13)
Quad screen ↓ AFP, ↑ hCG, ↓ estriol, ↑ inhibin → Down
All quad markers low → Edwards
↑ AFP alone → neural tube defect (or wrong dates, twins)
Recurrent Down in a young couple → Robertsonian translocation
Most common cause of Down → maternal meiosis I nondisjunction