Genotype-phenotype correlation of ODLURO syndrome comorbid epilepsy associated with KMT2E variations: Report on a novel case and systematic literature review.

Background: O'Donnell-Luria-Rodan (ODLURO) syndrome is a newly described neurodevelopmental disorder caused by a pathogenic KMT2E variant. The primary clinical phenotypes include developmental delay, intellectual disability (ID), and epilepsy. Epilepsy, observed in 29% of affected individuals, has not been thoroughly investigated. In this study, we describe the phenotypes and genetic profiles of patients with ODLURO syndrome and epilepsy.

Methods: We summarized and analyzed data from 30 patients with ODLURO syndrome and epilepsy from the systematic literature and DECIPHER database. Information regarding seizure classification, brain MRI findings, antiseizure medications, and genetics variations was collected and analyzed retrospectively.

Results: The risk factors associated with epilepsy in ODLURO syndrome remain unclear, and clinical heterogeneity exists. While focal seizures are most prevalent, various epilepsy classifications are observed. Brain MRI findings indicated that cerebral atrophy and cystic changes were common, though no correlation with epilepsy was established. Among ten individuals with a record of antiseizure medication, approximately 70% required two or more antiseizure medications.

Conclusions: A clear genotype-phenotype correlation remains elusive even among individuals with the same KMT2E variation. The pathogenesis of epilepsy associated with KMT2E variation is complex and necessitates further molecular genetic studies to elucidate the mechanisms underlying these genetic disorders. This research provides essential evidence for specific and individualized treatment approaches.