Prenatal Detection of Trisomy 2: Considerations for Genetic Counseling and Testing

Area of Science:

• Genetics
• Prenatal Diagnosis
• Medical Genetics

Background:

• Non-invasive prenatal testing (NIPT) is increasingly used for fetal aneuploidy screening.
• Targeted NIPT panels may miss rare chromosomal abnormalities like trisomy 2.
• Accurate genetic counseling and testing algorithms are crucial for managing high-risk pregnancies.

Observation:

• A pregnant patient with abnormal first-trimester markers refused invasive testing, opting for targeted NIPT which showed low risk.
• Serial ultrasounds revealed fetal growth retardation, oligohydramnios, and other anomalies suggestive of chromosomal abnormality.
• Whole-genome sequencing NIPT and placental biopsy revealed trisomy 2, but invasive testing was unfeasible due to complications.

Findings:

• Conventional cytogenetics confirmed low-level true fetal mosaicism for trisomy 2 (0.6% in fetal tissues) with placental mosaicism (83.2%).
• Whole-genome sequencing NIPT detected trisomy 2, unlike the initial targeted NIPT.
• Pathological examination of the aborted fetus showed severe structural abnormalities consistent with trisomy 2.

Implications:

• Whole-genome sequencing NIPT offers broader detection of aneuploidies compared to targeted NIPT in high-risk pregnancies.
• Distinguishing true fetal mosaicism from placental-confined mosaicism is critical for accurate genetic counseling.
• High-resolution ultrasound is vital for decision-making when invasive sampling is impossible due to oligohydramnios or fetal growth restriction.