De novo ANKRD11 and KDM1A gene mutations in a male with features of KBG syndrome and Kabuki syndrome

KBG syndrome is a rare, autosomal dominant disorder caused by mutations or deletions leading to haploinsufficiency for the Ankrin Repeating Domain‐Containing protein 11 ( ANKRD11 ) at chromosome 16q24.3. Kabuki syndrome is caused by mutations or deletions of lysine (K)‐specific methyltransferase 2D ( KMT2D ) and lysine‐specific methylase 6A ( KDM6A ). We report on a male with developmental delays, cleft palate, craniofacial dysmorphism, hypotonia, and central nervous system anomalies including diminished white matter with thinning of the corpus callosum. Exome sequencing revealed a de novo mutation in ANKRD11 , c.2606_2608delAGA, predicting p.Lys869del and an additional, de novo mutation, c.2353T>C, predicting p.Tyr785His in KDM1A , a gene not previously associated with a human phenotype. We describe this child as the first report of a deleterious sequence variant in KDM1A and hypothesize that his phenotype resulted from the combined effect of both mutations. © 2014 Wiley Periodicals, Inc.