Developmental and epileptic encephalopathies with germline

Background: Diseases associated with the germline Methods: We identified five germline missense pathogenic/likely pathogenic variants in Results: In all probands, the clinical symptoms included early-onset epilepsy, hypotonia, dysmorphic features, and variable congenital anomalies. A literature review of 107 cases supports reclassification of the phenotypic spectrum into severe (15.9%), intermediate (72.0%), and milder (12.1%) categories. Notably, the phenotypes of the five cases were classified as severe (n = 2) or milder (n = 3), consistent with prior reports, but revealed population-specific traits such as universal febrile sensitivity and normal serum alkaline phosphatase levels that are in contrast to elevated levels often noted in Western cohorts. The three children with the milder phenotype were found to have pathogenic/likely pathogenic variants located in exon 2, while the two severe phenotypes showed these variants located in exons 3 and 5. Conclusion: Overall, we report three novel pathogenic/likely pathogenic variants that expand clinicians' understanding of the genetic diversity within this phenotypic spectrum. These insights are expected to be valuable for future pathogenic/likely pathogenic variant analysis and accurate classification of clinical subtypes, which would help improve the understanding of