Prenatal diagnosis of Walker–Warburg syndrome due to compound mutations in the B3GALNT2 gene

BACKGROUND: Congenital hydrocephalus is one of the symptoms of Walker–Warburg syndrome that is attributed to the disruptions of the genes, among which the B3GALNT2 gene is rarely reported. A diagnosis of the Walker–Warburg syndrome depends on the clinical manifestations and the whole‐exome sequencing after birth, which is unfavorable for an early diagnosis. METHODS: Walker–Warburg Syndrome was suspected in two families with severe fetal congenital hydrocephalus. Whole‐exome sequencing and Sanger sequencing were performed on the affected fetuses. RESULTS: The compound heterozygous variants c.1A>G p.(Met1Val) and c.1151+1G>A, and c.1068dupT p.(D357*) and c.1052 T>A p.(L351*) in the B3GALNT2 gene were identified, which were predicted to be pathogenic and likely pathogenic, respectively. Walker–Warburg syndrome was prenatally diagnosed on the basis of fetal imaging and whole‐exome sequencing. CONCLUSIONS: Our findings expand the spectrum of pathogenic mutations in Walker–Warburg syndrome and provide new insights into the prenatal diagnosis of the disease.