Molecular Analysis of SCN1A Gene Variants Associated with Dravet Syndrome: Implications for Diagnosis and Management.

Clinical phenotype spectrum and prognostic analysis of DNM1L-related disorders: a single-center cohort study of 18 patients

To summarize the clinical and genetic characteristics of DNM1L -related disorders and explore genotype-phenotype correlations and prognosis. We retrospectively analyzed clinical data from 18 children with DNM1L variants diagnosed between 2015 and October 2025. Combined with systematic literature review (2007-October 2025) to analyze reported DNM1L variant types and clinical phenotypes. The cohort included 18 children (10 male, 8 female) with a median onset age of 3.5 years. Epilepsy occurred in 88.9% of patients, with 72.2% developing super-refractory status epilepticus; 66.7% had dystonia. Most patients exhibited brain MRI and EEG abnormalities. Eight novel pathogenic variants were identified (four missense, three frameshift, one compound heterozygous). Notably, eight patients with middle domain variants (primarily p.Arg403Cys) presented a novel “hemiconvulsion-hemiplegia-epilepsy syndrome” phenotype. At last follow-up, 83.3% had a modified Rankin Scale score ≥4, indicating severe disability and poor prognosis. Literatures review confirmed DNM1L variants are predominantly missense, with the middle domain as a hotspot. The p.Arg403Cys variant is recurrent and highly prevalent in the Chinese. Middle domain variants are more common in Asians, while GTPase domain variants are more frequent in Europeans. Missense variants in the middle domain correlated with higher rates of neurological dysfunction and mortality. This study represents an extension of our earlier work by incorporating an additional 18 cases, which expands the genetic and phenotypic spectrum of DNM1L -related disorders. It identifies “hemiconvulsion-hemiplegia-epilepsy syndrome” as a distinct feature and potential prognostic indicator for middle domain variants. The established genotype-phenotype patterns, based on protein domains and ethnic differences, provide critical insights for precise diagnosis and management.

[Clinical and genetic characteristics and genotype-phenotype correlations of pheochromocytoma and paraganglioma in children and adolescents].

Clinical heterogeneity and diagnostic challenges in CASK-related neurodevelopmental disorders: a longitudinal observational study

CASK-related disorders may present with severe neurodevelopmental impairment and cerebral palsy–like phenotypes, even in the absence of characteristic neuroimaging findings, which should raise suspicion for CASK-related disorders.

From targeted SCN1A analysis to whole exome sequencing: clinical utility and novel genetic findings in a Hungarian paediatric epilepsy cohort

Epilepsy represents a highly prevalent neurological disorder with a significant genetic component, particularly implicating ion channel genes, including SCN1A. In this study, 431 individuals with heterogeneous paediatric-onset epilepsy phenotypes were assessed at the Department of Medical Genetics, University of Pécs between 2018 and 2024. Genetic investigations employed Sanger sequencing, targeted epilepsy gene panels, whole exome sequencing, and multiplex ligation-dependent probe amplification for SCN1A copy number analysis. Thirty-six pathogenic or likely pathogenic SCN1A variants were identified, including 15 variants which have not been reported previously. Furthermore, 9 novel variants were detected in 12 additional epilepsy-associated genes. Diagnostic yield was proportional to the breadth of genomic interrogation. WES analysis revealed 6 novel variants in 19 genes. These findings underscore the considerable genetic heterogeneity of epilepsy and demonstrate the clinical utility of gene panels and WES, particularly in complex phenotypes. The identification of novel variants enhances molecular understanding and facilitates more precise genotype-phenotype correlations, reinforcing the value of comprehensive genomic diagnostics in epilepsy management.

Beyond Rett syndrome: a case series expanding the neurological spectrum associated with pathogenic MECP2 variants

[Clinical and genetic analysis of a child with MRXS34 syndrome due to variant of NONO gene].