Dual Diagnosis of Sifrim-Hitz-Weiss Syndrome and Neurofibromatosis Type 1: Expanding the Phenotype of Cardiac Features in Sifrim-Hitz-Weiss Syndrome and Quick Literature Review.

Abstract

Sifrim-Hitz-Weiss syndrome (SIHIWES) is a rare autosomal dominant disorder characterized by neurodevelopmental delay and variable congenital defects, including cardiac and skeletal, caused by mutations in the CHD4 gene. Neurofibromatosis type 1 (NF1) is a well-known disease characterized by cafe-au-lait spots and fibromatous tumors of the skin caused by heterozygous mutations in the NF1 gene. We report a male patient, 6 months old at the time of the first examination and 4.5 years old at the time of the second examination, with dysmorphic facial features, multiple café-au-lait spots, bilateral postaxial polydactyly, hydrocephalus, and dextrocardia. Whole exome sequencing revealed a de novo heterozygous c.4256G>A (p.Arg1419His) variant in the CHD4 and a heterozygous c.1411A>T (p.Lys471Ter) variant in the NF1 gene, compatible with the dual diagnosis of NF1 and SIHIWES. Although congenital heart anomalies have been reported as a component of SIHIWES, dextrocardia is a novel finding that has not previously been reported in this syndrome. Adding dextrocardia to the previously described findings, including polydactyly and hydrocephalus, suggests that a gene related to ciliary function may be a downstream target of CHD4.