SF3B2 Haploinsufficiency Associated With Hirschprung Disease and Complex Cardiac Defect Without Craniofacial...

Haploinsufficiency of SF3B2 is associated with craniofacial microsomia, characterized by mandibular hypoplasia and microtia, often with preauricular tags or pits, epibulbar dermoids, and cleft palate. In addition, extracraniofacial anomalies may be present, such as skeletal, cardiac renal, and abnormalities of the central nervous system. Variants have been either de novo or inherited, and both inter- and intrafamilial variability has been observed. Here we describe a patient referred for exome sequencing for a complex congenital heart defect and Hirschsprung disease found by exome sequencing to be heterozygous for a loss of function variant, c.945dup (p.Val316SerfsTer5), in SF3B2. This variant was inherited from a parent with an isolated cardiac defect. Interestingly, neither have the defining craniofacial features or other dysmorphisms. This report further illustrates the degree of phenotypic variability seen in SF3B2-related disease and expands the spectrum to include Hirschsprung disease.