Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation

Abstract

Objective To explore the clinical features and genetic characteristics of myoclonic-atonic (MAE) caused by gene mutation. Methods The clinical data of a patient with 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 gene mutation and the clinical phenotype of children with myoclonic-atonic 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 gene. A total of 27 cases including the present case with 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 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 gene mutations is absence and atonic seizures, cognition before 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. Key words: Epilepsies, myoclonic; Epilepsy, absence; Glucose transporter type 1; Mutation; Child