A Novel KMT5B Frameshift Variant Presenting with Autism and Psychiatric Features: Intrafamilial Phenotypic Variation - A Case Report.

Abstract

Introduction: Pathogenic variants in the KMT5B gene, encoding a lysine methyltransferase involved in chromatin remodeling, have been associated with intellectual disability, autism spectrum disorder, and various craniofacial features. However, the detailed genotype-phenotype correlations have yet to be fully elucidated.

Case presentation: We report a four-year-old male patient who presented with developmental delay, impaired social interaction, repetitive behaviors, and language delay. Whole-exome sequencing identified a novel heterozygous frameshift variant in KMT5B (c.618del; p.Glu206Aspfs*7). Segregation analysis revealed that the patient's father also carried the same variant and exhibited intellectual disability and obsessive-compulsive disorder.

Conclusion: By presenting a novel KMT5B variant alongside an atypical adult neuropsychiatric presentation, this report broadens both the variant and phenotypic spectrum of KMT5B haploinsufficiency. It further underscores the potential for neurobehavioral manifestations to extend beyond childhood, advocating for sustained clinical surveillance and age-spanning neuropsychiatric assessment.