Prenatal Phenotype of a Heterozygous Missense CHD4 Variant in a Fetus With Widened Cerebral Subarachnoid Space, Increased Head Circumference and Polyhydramnios

Abstract

CHD4-associated Sifrim-Hitz-Weiss syndrome (SIHIWES) is an autosomal dominant intellectual developmental disorder. The postnatally clinical manifestations primarily include heart defects, macrocephaly, and hypotonia. We report a well-documented prenatal case of SIHIWES presenting with increased head circumference, polyhydramnios, and widened cerebral subarachnoid spaces. Trio-based whole exome sequencing identified a de novo likely pathogenic variant in CHD4, confirming the diagnosis of SIHIWES in the fetus. Our report expands the prenatal phenotypic spectrum of SIHIWES and highlights the importance of considering whole exome sequencing in fetuses presenting with polyhydramnios, macrocephaly, and widened cerebral subarachnoid spaces.