A 32-year-old G2P1 woman undergoes routine chorionic villus sampling (CVS) at 11 weeks for advanced maternal age. The CVS karyotype returns **46,XX/47,XX,+16** (marked as **A** in the diagram) in 40% of cytotrophoblast cells. Follow-up amniocentesis at 16 weeks reveals a normal 46,XX karyotype in cultured amniocytes. Serial growth ultrasounds at 24, 28, and 32 weeks show progressive intrauterine growth restriction (IUGR) with abdominal circumference falling from the 25th to the

Question

A 32-year-old G2P1 woman undergoes routine chorionic villus sampling (CVS) at 11 weeks for advanced maternal age. The CVS karyotype returns **46,XX/47,XX,+16** (marked as **A** in the diagram) in 40% of cytotrophoblast cells. Follow-up amniocentesis at 16 weeks reveals a normal 46,XX karyotype in cultured amniocytes. Serial growth ultrasounds at 24, 28, and 32 weeks show progressive intrauterine growth restriction (IUGR) with abdominal circumference falling from the 25th to the <3rd centile. Umbilical artery Doppler shows elevated S/D ratio but maintained end-diastolic flow.

Which of the following BEST describes the clinical significance of the karyotype abnormality marked **A**?

Accepted Answer

C. Confined placental mosaicism with normal fetal karyotype — IUGR results from impaired placental function despite fetal chromosomal normality; uniparental disomy must be excluded. ## Why option 1 is correct

The karyotype marked **A** — 46,XX/47,XX,+16 — represents **confined placental mosaicism (CPM) for trisomy 16**. The critical clinical finding is that CVS shows mosaic trisomy 16 in cytotrophoblast cells, but the follow-up amniocentesis reveals a **normal 46,XX fetal karyotype**. This dissociation defines CPM: the chromosomal abnormality is present in the placenta (derived from trophoblast) but absent from the fetus (derived from epiblast). Trisomy 16 is the most common autosomal trisomy at conception (~1% of pregnancies) but is universally lethal in non-mosaic form; most miscarry in the first trimester. When trisomy 16 arises post-zygotically and is then selectively lost from the fetal cell line via trisomy rescue, the pregnancy can continue, but the surviving placenta retains trisomic cells. This impairs placental function, causing the observed IUGR, oligohydramnios, and increased risk of stillbirth and preeclampsia. The normal amniocentesis is reassuring for the fetus, but **uniparental disomy (UPD) for chromosome 16 must be excluded** — trisomy rescue can leave the fetus with two copies from one parent, and maternal UPD16 is associated with IUGR even with a disomic karyotype. (Williams Obstetrics 26e, Prenatal Diagnosis chapter)

## Why each distractor is wrong

- **Option 2**: Incorrect. The amniocentesis explicitly shows a normal 46,XX fetal karyotype, ruling out universal fetal trisomy 16. Termination is not indicated when the fetus is chromosomally normal; the pregnancy is managed with intensive surveillance.
- **Option 3**: Maternal contamination would not explain the consistent mosaic pattern in 40% of cytotrophoblast cells or the progressive IUGR on serial ultrasounds. The normal amniocentesis result is not due to contamination but reflects true fetal normality with placental mosaicism.
- **Option 4**: The amniocentesis result (normal 46,XX) definitively excludes trisomy 16 in the fetus. Fetal echocardiography is not the gold standard for diagnosis of chromosomal abnormalities; karyotyping and FISH are. This option conflates placental and fetal involvement.

**High-Yield:** Confined placental mosaicism (CPM) for trisomy 16 = mosaic trisomy in placenta + normal fetal karyotype on amniocentesis + IUGR from placental dysfunction + must exclude UPD16.

[cite: Williams Obstetrics 26e — Prenatal Diagnosis]

Answer

A. Universal fetal trisomy 16 with poor prognosis — termination of pregnancy is recommended regardless of amniocentesis results

Answer

B. Maternal contamination of CVS sample — repeat amniocentesis is diagnostic and the pregnancy carries no additional risk

Answer

D. Trisomy 16 in both placenta and fetus — amniocentesis is unreliable and fetal echocardiography is the gold standard for diagnosis

Explanation

Why option 1 is correct

Why each distractor is wrong

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