Clinical findings
Developmental delay (DD) is the most prevalent clinical feature but varies from mild to severe among affected individuals. Many children with SLC6A1-NDD come to medical attention with hypotonia and delayed motor and language milestones within the first year of life.
Language development is often more delayed than motor development.
Some children with SLC6A1-NDD have developmental regression that is either episodic, with recovery of skills, or followed by a plateau in development.
Intellectual disability (ID). Approximately one third of individuals will have ID; severity varies from mild to severe. Many of those who do not meet the criteria for ID will have a specific learning disorder such as dyslexia or dysgraphia.
Other neurodevelopmental manifestations. Approximately one third of individuals have autism spectrum disorder, and 10%-20% have attention-deficit/hyperactivity disorder.
Epilepsy. Several seizure phenotypes have been reported in individuals with SLC6A1-NDD:
• Early-onset absence epilepsy / childhood absence epilepsy.
• Myoclonic and atonic seizures.
• Developmental and epileptic encephalopathy (DEE).
• Focal epilepsy.
• Age of onset is typically early childhood.
Movement disorders. Approximately half of individuals with SLC6A1-NDD have abnormal movements.
Behavioral issues are common in individuals with SLC6A1-NDD and likely have a significant contribution to the burden of disease.
Gastrointestinal issues.
Other
• Psychiatric features. A small number of adults with an SLC6A1 pathogenic variant have been diagnosed with schizophrenia.
Prognosis
Life expectancy is not reduced. Seizure may be refractory to anti-seizure medications. Some individuals are incapable of independent living.
SLC6A1