Prenatal Diagnosis of Autosomal Recessive Primary Microcephaly Type 2 Caused by Compound Heterozygous WDR62 Variants in a Family With Two Recurrent Cases.

OBJECTIVE

Autosomal recessive microcephaly type 2 (MCPH2), caused by biallelic WDR62 variants, is a rare neurodevelopmental disorder typically described postnatally. We aimed to delineate its prenatal phenotype via data from two affected fetuses in a family.

METHODS

Trio whole-exome sequencing (WES) was performed on one fetus and his parents. Variants were prioritized via population databases, computational predictions, and segregation analysis, which were confirmed via Sanger sequencing.

RESULTS

Prenatal imaging revealed microcephaly, agenesis of the corpus callosum, and neuronal migration defects (lobar holoprosencephaly and lissencephaly) in two fetuses. Trio-WES identified compound heterozygous WDR62 variants (c.1128C > A/p.Cys376* and c.643A > C/p.Thr215Pro) in one fetus, each inherited from a heterozygous parent. Sanger sequencing confirmed variants in both fetuses and parents.

CONCLUSIONS

Trio-WES is crucial for the prenatal diagnosis of fetuses with unresolved sonographic anomalies. We report the prenatal features and molecular diagnoses of MCPH2, expanding its prenatal phenotypic spectrum and enhancing its clinical genomic database utility.