SLC6A1–Related Neurodevelopmental Disorder: A Scoping Review of Clinical Features and Emerging Therapeutic Strategies

BACKGROUND: Solute carrier family 6 member 1 (SLC6A1) gene encodes gamma-aminobutyric acid transporter 1 (GAT-1), the principal synaptic gamma-aminobutyric acid (GABA) transporter. Pathogenic heterozygous loss-of-function variants of SLC6A1 cause a developmental and epileptic encephalopathy characterized by early-onset epilepsy, intellectual disability, and autistic features. Despite a rapidly expanding translational pipeline, clinical evidence remains fragmented. This scoping review systematically maps the published evidence on the phenotypic spectrum and therapeutic landscape of SLC6A1-related neurodevelopmental disorder. METHODS: A systematic search of PubMed, Embase, OVID/MEDLINE, Web of Science, and ClinicalTrials.gov was conducted through March 2026, supplemented by hand-searching reference lists and American Epilepsy Society conference abstracts (2019-2025). The review was conducted per the Arksey and O'Malley framework and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. RESULTS: Epilepsy affects approximately 90% of clinically identified individuals, with seizure onset typically between 14 months and 5 years; predominant types include absence (60-72%), myoclonic-atonic (24-35%), and atonic seizures. Intellectual disability or developmental delay is present in 82-100% of patients, with cognitive impairment antedating seizure onset in over 60% of cases. Autistic features occur in 22-65% and hypotonia in 60-71%. Clinical severity correlates with degree of residual GAT-1 activity as follows: variants with near-total loss of GABA uptake (