GABRA1 gene variant detected for a patient with treatment-resistant epilepsy: a case report
GABRA1 (OMIM #137160) is a gene, located at chromosome 5q34, that encodes the alfa-1 receptor subunit of GABA. Variants that impair the function of this gene lead to treatment-resistant epilepsy and various degree of developmental delay, and autistic features. Idiopathic generalized epilepsy accounts for 30% of all epilepsies. We present an observed GABRA1 gene variant and its impact on the patient's health. Case Description. Our patient is a 9-year-old girl. She is diagnosed with developmental delay from infancy, predominantly speech impairment. At age 1 she presented with short seizures, manifesting differently. At first, it would recur 10-15 times a day. Sodium valproate was prescribed. It had a short-term effect but led to seizures recurring 90 times daily. In an attempt to control the seizures - polytherapy was indicated. Sleep EEG was performed - multifocal and generalized epileptiform activity were observed. Brain MRI showed likely terminal zones of myelination. The patient was diagnosed with idiopathic generalized epilepsy and showed resistance to therapy. When referred to a clinical geneticist consultation - whole exome sequencing (WES) with epilepsy & brain development disorders panel was performed and a missense heterozygous GABRA1 gene (NM_001127643.2) variant c.918G>T, p.Lys306Asn was detected and classified as likely-pathogenic. Parents' genetic testing results are unremarkable, therefore the variant is de novo. The patient's phenotype (OMIM #615744) and genetic testing results were compatible with a rare genetic epilepsy diagnosis. Summary A female patient, diagnosed with idiopathic generalized epilepsy and developmental delay was consulted suspecting a genetic etiology. WES was performed and a de novo like-pathogenic heterozygous GABRA1 gene variant was detected, confirming a developmental and epileptic encephalopathy 19. Conclusions. Genetic testing for patients, diagnosed with treatment-resistant epilepsy and developmental delay is crucial. It is necessary while determine the prognosis and treatment plan. In this case, the patient's condition is revised yearly.