Second-trimester detection of Mowat-Wilson syndrome using comparative genomic hybridization microarray testing.

Area of Science:

• Prenatal Diagnosis
• Medical Genetics
• Fetal Medicine

Background:

• Increased nuchal translucency in fetuses can indicate underlying genetic abnormalities not detected by standard karyotyping.
• Conventional cytogenetic studies may miss subtle genetic defects, necessitating advanced diagnostic methods.
• Microarray comparative genomic hybridization (array CGH) offers enhanced resolution for identifying submicroscopic chromosomal imbalances.

Observation:

• A fetus presented with significant nuchal translucency and ambiguous genitalia at 13 weeks gestation.
• Initial fetal karyotyping revealed a de novo inversion (46,XY,inv(1)(p31q42)).
• Array CGH identified a ZEB2 gene deletion at 2q22.3, indicative of Mowat-Wilson syndrome.

Findings:

• Array CGH successfully detected a ZEB2 gene deletion, a cause of Mowat-Wilson syndrome, in a fetus with increased nuchal translucency and a normal karyotype.
• The ZEB2 deletion was confirmed as the underlying genetic cause after initial conventional karyotyping was inconclusive for microdeletions.
• This case highlights the diagnostic utility of array CGH in identifying genetic causes for fetal anomalies.

Implications:

• Array CGH serves as a valuable complementary tool for prenatal diagnosis in cases of increased nuchal translucency with normal karyotypes.
• Early and accurate genetic diagnosis can inform clinical management and reproductive decisions.
• Advanced genomic technologies like array CGH are crucial for diagnosing rare genetic disorders prenatally.