Background: In recent years, many new candidate genes are being identified as putative pathogenic factors in children with developmental delay and autism. Recently, heterozygous mutations in the KMT2E gene have been identified as a cause of a unique neurodevelopmental disorder with variable combination of global developmental delay or isolated speech delay, intellectual disability, autistic features, and seizures.
Methods: Here, we present two new cases of KMT2E mutation-associated neurodevelopmental disorder in a 4-year-old girl and 5-year-old boy. We also performed a pooled review of the previously published cases of KMT2E-related neurodevelopmental disorder. Articles were identified through search engines using appropriate search terms.
Results: Along with the presented 2 cases, 40 cases were analyzed. Out of them, 30, 6, and 4 children had protein-truncating mutations, missense mutations, and copy number variants, respectively. The common features were global developmental delay (97%) followed by macrocephaly (35%), seizures (30%), and autism (25%). Children with missense variants had severe phenotype, with microcephaly, profound developmental delay, and increased frequency of seizures. Neuroimaging revealed nonspecific changes, including cerebral white matter signal abnormalities.
Conclusion: KMT2E-related neurodevelopmental disorder remains one of the clinical differentials in children with global developmental delay and/or autistic features/seizure. With the reporting of more cases in the future, the already heterogeneous clinical spectrum of this disease is likely to be widened.
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