By: Clare Logan
What is the SLC6A1 Gene?
The SLC6A1 gene plays a critical role in keeping the brain’s activity balanced. It provides instructions for making a protein called GABA transporter 1 (GAT-1), which helps regulate levels of GABA, a chemical messenger that calms down brain activity. After GABA sends its message between neurons, GAT-1 brings it back into nerve cells so it can be reused or broken down. This process keeps GABA levels in the brain at the right balance.
When the SLC6A1 gene doesn’t function properly, often due to a random genetic variant, GAT-1 cannot do its job efficiently. As a result, GABA stays in the synapse too long or too little, disrupting normal brain signaling. This disruption can cause too much excitability in the brain, which is directly linked to epileptic seizures. These gene variants are also associated with developmental delays and other neurological symptoms, usually beginning in early childhood.
SLC6A1-Related Epilepsy
Epilepsy related to SLC6A1 changes is rare and often shows up as myoclonic-atonic epilepsy (MAE), also known as Doose syndrome. Children typically begin showing signs between 6 months and 3 years of age. Symptoms often include frequent seizures, such as sudden jerks, muscle weakness, or brief staring spells, that are caused by abnormal bursts of brain activity due to imbalanced GABA signaling.
Beyond seizures, many children experience developmental delays, especially in language and motor skills. Additionally, behavior challenges, including ADHD, autism-like features, and anxiety, are also common. These additional symptoms are thought to be related to the same GABA-related brain circuit disruptions that cause epilepsy.
Recent research shows how much the effects of SLC6A1 gene variants can vary between individual children. A 2024 study by Dr. Ream Goodspeed reported that 93% of children with these variants had significant speech delays, with many speaking fewer than 10 words by age two. Over 90% had learning difficulties, and 76% were diagnosed with autism. Another survey by Dr. Sharon Kahen found similar trends: high rates of ADHD (52%), anxiety (54%), and behavioral issues (60%). Because the symptoms overlap with other developmental disorders, many families face delayed or incorrect diagnoses, making it harder to start helpful treatments early.
Research and Treatment
Treatment for SLC6A1-related epilepsy is still developing. Seizure medications such as valproic acid, levetiracetam, and ethosuximide are commonly used, but their effectiveness can vary, since the root of the problem lies in the way GABA is processed in the brain. Researchers are exploring new treatments that go beyond managing symptoms, including gene therapies and targeted drugs that aim to restore normal GABA function. These approaches could better address the underlying cause of seizures and other symptoms.
Because children with SLC6A1-related conditions often face both medical and educational challenges, experts recommend a multidisciplinary care team, including, but not limited to, neurologists, speech and occupational therapists, behavioral specialists, and educators, to create personalized support plans. Though SLC6A1-related disorders are newly recognized, awareness is growing. Families, doctors, and researchers are working together to improve diagnosis, increase treatment options, and support those affected.
Resources:
“What Is SLC6A1?” SLC6A1 Connect, www.slc6a1connect.org/what-is-slc6a1. Accessed 4 Mar. 2025.
Johannesen, Katrine M., et al. “Defining the phenotypic spectrum of SLC6A1 mutations.” Epilepsia, vol. 59, no. 2, 2018, pp. 389–402. doi:10.1111/epi.13970.
“SLC6A1 Neurodevelopmental Disorder.” Genetic and Rare Diseases Information Center (GARD), U.S. Department of Health and Human Services, rarediseases.info.nih.gov/diseases/13340/slc6a1-neurodevelopmental-disorder. Accessed 4 Mar. 2025.
Goodspeed, Ream J., et al. “Parent-Reported Phenotypes in 43 Children with SLC6A1 Variants.” Epilepsia Open, vol. 9, no. 1, 2024, pp. 148–156. doi:10.1002/epi4.12754.
Kahen, Sharon, et al. “Phenotypic and Clinical Characteristics of Children with SLC6A1-Related Disorder: A Caregiver Survey Study.” Epilepsy & Behavior, vol. 145, 2024, 109399. doi:10.1016/j.yebeh.2024.109399.
