Prenatal presentation of Walker–Warburg syndrome with a POMT2 mutation: an extended fetal phenotype

Abstract

Abstract Background Walker–Warburg syndrome (WWS) is a rare, lethal, genetically, and clinically heterogeneous congenital muscular dystrophy resulting from defective glycosylation of α-dystroglycan (α-DG) and is associated with both cranial and ocular malformations. Prenatal detection of posterior fossa anomalies in association with hydrocephalus are nonspecific, however, an additional finding of eye anomalies are typical for WWS. The purpose of this report is to elucidate the pattern of associated malformations in a fetus with WWS born to 3rd degree consanguineously married couple. Additionally, the fetal ultrasonography revealed congenital heart disease, clenched hands, and talipes equinovarus; these findings have not been previously reported and represent an expansion of prenatal spectrum associated with WWS. Case presentation We report on a specific sonographic pattern of congenital anomalies including hydrocephalus, agenesis of corpus callosum, and Dandy–Walker malformation. Ocular abnormalities include microphthalmia, cataract, and an echoic structure suggestive of persistent primary vitreous. Other features include congenital heart disease, unilateral multicystic kidney, and previously unreported findings of bilateral clenched hands and talipes equinovarus. The molecular analysis detected a homozygous splicing mutation, c.924-2A>C, in the POMT2 gene; this variant segregated with the phenotype. Conclusion WWS syndrome has characteristic prenatal ultrasound findings which can improve the prenatal identification of this condition and help in guiding the molecular diagnosis and counseling. The detection of bilateral clenched hands and talipes equinovarus is a novel finding that further expands the phenotypic spectrum of WWS.