New Insights into Inherited SYNGAP1-Related Disorders and Their Genetic Origins

Researchers from Children's Hospital of Philadelphia have uncovered important findings regarding SYNGAP1-related disorders, a spectrum of neurodevelopmental conditions often associated with epilepsy, developmental delays, intellectual impairments, and behavioral differences such as autism spectrum disorder. While most cases of these disorders arise from spontaneous, de novo genetic mutations, recent studies have identified rare instances where the causative variants are inherited from a parent. This discovery has significant implications for genetic counseling, family planning, and the classification of genetic variants.

The study, published in the journal Epilepsia, analyzed eight individuals across three families who carried inherited, protein-truncating variants in the SYNGAP1 gene. In two families, the affected individual inherited the mutation from a heterozygous parent displaying symptoms consistent with SYNGAP1-related disorders. In a third case, the parent carried a mosaic mutation, meaning only a subset of their cells contained the variant, and they showed no symptoms. Additionally, the study examined families with missense variants—where an amino acid substitution occurs—and highlighted the need for further research to determine the clinical significance of these variants.

This ongoing research, part of the SYNGAP1 ProMMiS natural history study, aims to include as many individuals with SYNGAP1 mutations as possible to monitor disease progression and facilitate future clinical trials. The findings emphasize that while inherited variants are rare, they offer valuable insights into the genetic and clinical diversity of SYNGAP1-related disorders. For families affected by these conditions, understanding the potential for inherited mutations can improve genetic counseling and guide decisions about future pregnancies.

Overall, the discovery underscores the importance of accurate genetic variant classification and highlights the complexities of neurogenetic disorders, paving the way for more personalized approaches to treatment and care.

Source: https://medicalxpress.com/news/2025-06-instances-syngap1-disorders-inherited-genetic.html