Kleefstra syndrome 2 in an adult

The Kleefstra syndrome spectrum (KSS) is a group of neurodevelopmental disorders characterized by intellectual disability, behavioral disorders, growth and neurodevelopmental delay, facial dysmorphism and neurological deficits. Kleefstra syndrome 2 (KLEFS2) causes KSS and is due to heterozygous nonsense variants in the KMT2C gene. We report the long-term clinical course and multi-organ manifestations of a patient with KLEFS2 caused by a novel heterozygous pathogenic variant in KMT2C. Methods A patient with KSS phenotype develops proteinuria with progressive kidney dysfunction secondary to focal segmental glomerular sclerosis. She subsequently developed recurrent episodes that mimicked mitochondrial stroke-like episodes, featured by encephalopathy, stroke-like episodes with complex partial status epilepticus associated with cortical and subcortical T2/FLAIR signal hyperintensities that partially responded to intravenous arginine infusions. Results Exome sequencing revealed a novel heterozygous pathogenic nonsense variant in KMT2C c.3940C>T (p.Glu1314Ter). Nuclear and mitochondrial DNA variants associated with mitochondrial disorders have been excluded. Discussion This is a case of KLEFS2 with longitudinal 10 year follow up and its multi-organ clinical manifestations not previously reported. Our report further expands the genotypic and phenotypic spectrum of KLEFS2.