SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) is an autosomal dominant disorder typically caused by a de novo pathogenic variant.
Molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.
If inherited, penetrance appears to be incomplete.
SLC6A1 encodes the sodium- and chloride-dependent GABA transporter 1 (GAT-1), which is responsible for the reuptake of GABA into presynaptic neurons and glia. GABA is the principal inhibitory neurotransmitter that counterbalances neuronal excitation in the brain. The exact mechanism of molecular pathology is not yet fully understood; however, it is known that disruption of this inhibitory balance can result in seizure.
Mechanism of disease causation. Loss of function
No genotype-phenotype correlations have been identified to date. However, ongoing studies suggest that the level of GAT-1 function (see Molecular Genetics) may correlate with disease severity, such that those with lower residual GAT-1 function have the most severe manifestations of SLC6A1-NDD
SLC6A1