Prenatal diagnosis of SMPD4 loss ‐ A neurodevelopmental disorder with microcephaly, arthrogryposis and structural brain anomalies

Abstract

AbstractSMPD4 loss is a rare neurodevelopmental disorder that leads to severe mental and physical disability and early death in infancy. Most cases of this genetic condition have been diagnosed postnatally. This article focuses on the prenatal findings of affected fetuses. The phenotypes can include growth restriction, arthrogryposis (clenched hands, foot deformity), as well as cerebral abnormalities (simplified gyral pattern/lissencephaly, cerebellar hypoplasia, corpus callosum deformity). SMPD4 loss is detectable via exome sequencing. Here, two fetuses displayed a homozygotic pathogen variant in the SMPD4 gene, encoding for the enzyme Sphingomyelinase‐4. Both parents were heterozygous carriers of the pathogenic variant. On detection of the above mentioned signs exome sequencing is indicated, with focus on the SMPD4 gene.