Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

ABSTRACT

Objective@#To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.@*Methods@#The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords " SLC6A1" and " myoclonic-atonic epilepsy" . The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.@*Results@#A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in SLC6A1 gene. A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before epilepsy onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear.@*Conclusions@#The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures, cognition before epilepsy onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment.