Novel Variants in KMT2C Further Support a Neurodevelopmental Disorder Distinct From Kleefstra and Kabuki Syndromes

Heterozygous loss-of-function variants in the KMT2C gene were only recently recognized as a cause of neurodevelopmental disorder distinct from Kleefstra and Kabuki 1 syndromes. KMT2C-related neurodevelopmental disorder is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, seizures, craniofacial dysmorphism, and other comorbidities. Here we describe detailed phenotypes of three additional patients with novel variants in the KMT2C gene.

Using exome sequencing, we found two heterozygous variants c.3212G>A, p.(Trp1071*) and c.13204_13205delinsA, p.(Cys4402Ilefs*11) leading to premature stop codon and one heterozygous missense variant c.6517C>T, p.(Pro2173Ser) in the KMT2C gene (NM_170606.3) in patients with unrecognized neurodevelopmental disorder. Our patients suffer from developmental delay, speech delay, autism spectrum disorder, cognitive impairment, seizures, and/or craniofacial dysmorphism.

After detailed phenotype analysis and by comparison with previous reports, we found that our patients have very similar phenotypes as described before and thus further extend the list of KMT2C causal variants. Therefore, we believe that they fit into these previously described phenotypes of KMT2C-related Kleefstra syndrome 2 as well.