Long term follow-up of multiorgan disease in Kleefstra syndrome 2 in an adult - case report.

objectivesThe 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) is a part of KSS and is due to heterozygous loss-of-function variants in the KMT2 C 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 KMT2 C.

methodsA patient with KSS phenotype developed proteinuria with progressive kidney dysfunction secondary to focal segmental glomerular sclerosis. She subsequently developed recurrent episodes that mimicked mitochondrial stroke-like episodes. The phenotype included encephalopathy, stroke-like episodes with focal status epilepticus with impaired consciousness associated with cortical and subcortical T2/FLAIR signal hyperintensities that partially responded to intravenous arginine infusions.

resultsExome sequencing revealed a heterozygous pathogenic nonsense variant in KMT2 C (NM_170606.3) c.3940C > T (p.Gln1314Ter). 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 previously unreported multi-organ clinical manifestations including stroke-like episodes and nephrotic disease. Our report further expands the phenotypic spectrum of KLEFS2. Further reports of patients with KLEFS2 with multi-organ involvement should be sought to confirm our findings.