Intrafamilial variability in SLC6A1-related neurodevelopmental disorders

Introduction Phenotypic spectrum of SLC6A1 -related neurodevelopmental disorders ( -NDD) includes intellectual disability (ID), autistic (ASD), epilepsy, developmental delay, beginning from early infancy or after seizure onset, and other neurological features such as hypotonia movement disorders. Data on familial phenotypic heterogeneity have been rarely reported, thus in our study we aimed to investigate intrafamilial variability families with variants. Methods We collected clinical, laboratory genetic data 39 individuals, including 17 probands, belonging 13 harboring inherited variants . were through an international network Epilepsy Genetic Centers. Results Main clinical findings the whole cohort subjects were: (a) mainly presenting generalized seizures, reported 71% probands 36% siblings first/second-degree relatives. Within a family, same epilepsy type (generalized focal) was observed; (b) ID 100% 13% relatives, respectively; (c) learning disabilities detected 28% carriers, all them relatives proband; (d) around 51% presented psychiatric symptoms behavioral disorders, 82% probands. Out 19 patients symptoms, ASD diagnosed 40% them; (e) (primarily tremor speech difficulties) observed 38.5% cohort, 10 Our harbored 12 different variants, one frameshift, two stop-gain, while remaining missense. No genotype–phenotype associations identified. Discussion showed that first-or second-degree less severe phenotype, featuring mild and/or disabilities, at variance who suffered moderate ID, generalized, sometimes intractable, epileptic These may suggest proportion individuals -NDD might be missed, particular those older age where testing is not performed. Further studies are needed confirm results possibly expand these benefit counseling.