A Novel Truncating Variant in Sandestig-Stefanova Syndrome with Hydrocephalus

Abstract

<b><i>Introduction:</i></b> Sandestig-Stefanova syndrome (MIM:618804) is characterized by pre- and postnatal microcephaly, trigonocephaly, bilateral congenital cataracts, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, periventricular white matter loss, thin corpus callosum, and delayed myelination. Bi-allelic loss-of-function variants in the <i>Nucleoporin 188 (NUP188)</i> (MIM:615587) gene are implicated in the etiology. <b><i>Case Presentation:</i></b> Our patient, born to consanguineous parents, presented with tetralogy of Fallot, bilateral congenital cataracts, hydrocephalus, a bifid uvula, a right pelvic kidney, hepatomegaly, facial feature findings, and a history of a similarly affected ex-sibling. Whole exome sequence analysis in the index case revealed a novel homozygous variant NM_015354.2: c.124C>T/p.(Arg42Ter) in the <i>NUP188</i> gene. <b><i>Conclusion:</i></b> This study describes a new patient with Sandestig-Stefanova syndrome harboring a novel pathogenic variant in the <i>NUP188</i> gene.