Rationale:
To summarize the Clinical and Genetic Characteristics of patients with ATP6V1A related epilepsy.
Methods:
The clinical data of 10 patients with epilepsy associated with ATP6V1A variants who were admitted to the Neurological Department of Children’s Medical Center, Peking University First Hospital from January 2019 to December 2024 were analyzed. The children’s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.
Results:
Among the 10 patients, there were 4 males and 6 females. All 10 ATP6V1A variants were de novo heterozygous variants, including 1 case of chimeric variation (chimeric ratio 21.4%). A total of 9 different variants were involved (p.Asp100Asn, p.Pro249Ala, p.Ala251Thr, p.Phe252Ser, p.Asn314Ser, p.Ser352Ala, p.Trp354Leu, p.Gly414Asp, p.Arg571Cys). Except the variants p.Asn314Ser and p.Trp354Leu have been reported, the other 7 variants have not been reported yet, and p.Gly414Asp was found in 2 patients. The age of onset of epilepsy ranged from 15 days to 4 years old and 3 months old. Five patients (50%, 5/10) first presented with febrile convulsions, followed by multiple seizure types, including focal seizures in 6 cases, epileptic spasms in 4 cases, tonic spasm in 1 case, and atonic seizures in 1 case. Among them, 8 patients (80%, 8/10) have global developmental delay, and 2 patients (20%, 2/10) were diagnosed as ASD. EEG showed slow background in 6 cases, hypsarrhythmia in 3 cases, multifocal discharge in 5 cases, generalized discharge in 2 cases, focal discharge in 3 cases, epileptic spasm in 3 cases, tonic spasm in 1 case and atonic seizure in 1 case. MRI abnormalities were noticed in 4 patients, including frontotemporal cortical dysplasia in 3 cases, delayed myelination of white matter in 1 case, dysplasia of the corpus callosum in 1 case, bilateral ventricular enlargement in 1 case, mild cerebellar atrophy in 1 case. Eight patients diagnosed as developmental epileptic encephalopathy (DEE), and four of them were diagnosed as infantile epileptic spasm syndrome (IESS). At the last follow-up, the age ranged from 1 year and 7 months to 17 years. Six patients had seizure free (five patients had only focal seizures during the course of the disease), and four patients still had seizures after treatment with a variety of Antiseizure medications (ASMs).
Conclusions:
Patients with epilepsy associated with ATP6V1A variants have a wide range of age of onset. Common seizure types include focal seizures and epileptic spasms. Most patients have global developmental delay, and a few patients’ intellectual motor development are consistent with that of normal people. Patients with focal seizures are relatively easy to control (by using 1 or 2 ASMs), while patients with epileptic spasms are mostly drug refractory epilepsy.
Funding:
This study was supported by the National Key R&D Program of China (No. 2023YFC2706300, 2023YFC2706301).