To report the frequency of autism in our cohort of patients with SLC6A1 Neurodevelopmental Disorder (SLC6A1-NDD) and severity of symptoms as measured on validated scales.

SLC6A1-NDD is a rising cause of epilepsy and autism. SLC6A1 haploinsufficiency disrupts GABA homeostasis causing neurobehavioral changes that present with developmental delay and hypotonia, later with developmental regression and seizures. Autism is frequently diagnosed. Here we describe the prevalence and severity of autism in our cohort and describe adaptive abilities.

We reviewed patient records from SLC6A1-NDD specialty clinic and natural history study to determine the prevalence of autism. We extracted the scores of Childhood Autism Rating Scales, second edition (CARS-2) and Adaptive Behavior Assessment Systems, third edition (ABAS-3), providing a sample of autistic traits and adaptive abilities.

In our group of 35 SLC6A1-NDD patients (M16:F19), 23 carry a diagnosis of autism (65%). Of these, 10 patients are assigned a level 3 autism diagnosis and 8 with a level 2. A designated level was not available in 4 patients. Autism diagnosis was evenly split between male (11) and female (12) but 50% of female patients were given a level 3 autism diagnosis compared to 36% of male patients. CARS-2 scores ranged from 27 to 58 with an average of 39.1, consistent with severe autism. All but one CARS-2 scale was consistent with a diagnosis of autism. The mean General Adaptive Composite (GAC) score for the ABAS-3 was 70.9 (range 47-82), >2 standard deviations below the standard population mean.  

Beyond seizures, pathogenic variants in SLC6A1 correlate with autism; the present study demonstrates the highest association yet reported. Even without autism, adaptive skills are disrupted as illustrated by two patients who did not meet autism criteria but had ‘borderline’ and ‘below average’ GAC scores. This study expands the understanding of SLC6A1-NDD and expectations for patients.