TEMPORARY REMOVAL: Molecular and clinical Insights into KMT2E-Related O’Donnell-Luria-Rodan syndrome in a novel patient cohort

Le résumé fourni par la source

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.3 microdeletion encompassing the entire gene-locus. We further characterize both the clinical phenotype as well as its associated pathogenic variants' spectrum providing new information on sex-related phenotype distribution, according to the variant groups. We also highlight different epilepsy phenotype-genotype correlation with preferential association of generalized epilepsy and/or developmental and epileptic encephalopathy with missense pathogenic variants and focal epilepsy, childhood absence epilepsy and/or febrile seizures with pathogenic truncating variants and structural rearrangements. By a systematic review of the previously reported series, we also discuss previously unappreciated findings, including progressive macrocephaly, apraxia, and higher risk of bone fractures. • O'Donnell-Luria-Rodan syndrome is caused by KMT2E gene pathogenic variants. • Neurodevelopmental and behavioral manifestations are the main reported features. • Depicting a novel cohort, we further characterized its genotype-phenotype correlation. • Epilepsy semiology and novel findings are discussed in the text.

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