Familial Epilepsy Associated with Concurrent CHRNB2 Mutation and RBFOX1 Exon Deletion

Abstract

Abstract Background Understanding the genetic basis of epilepsy may lead to an improved understanding of the etiology, more precise medical management, and ultimately improved outcomes. It is imperative for patients with epilepsy to obtain a molecular diagnosis, especially when a strong familial epilepsy is discovered. Case presentation The proband was a 19 years old female who experienced focal onset seizures, with presenting symptoms of feeling dizzy, disorientation, and passing out. Her EEG studies revealed interictally focal slow and sharp waves in either the left or right hemisphere. EEG monitoring data showed that the seizures arose from the left fronto-temporal regions. Her brain MRI was normal. The proband sister also suffered from focal onset seizures. Her EEG showed focal epileptiform discharge in the right temporal regions, and a subsequent brain MRI was unrevealing. Two genetic tests were conducted for the proband: 1) array CGH revealed 16p13.3 deletion but no 22q deletion; and 2) NGS Epilepsy Panel revealed a few variants of uncertain significance (VUS) including in CHRNB2 (c.1423A >G, p.Ile475Val) and RBFOX1 (exon1-2 deletion). The proband’s sister also carries both the CHRNB2 variant and RBFOX1 deletion. The proband’s father carries the CHRNB2 variant her brother and her mother carry the deletion of RBFOX1. Conclusions In this family, the co-expression of the CHRNB2 variant and RBFOX1 deletion may cause the clinical seizures seen in the proband and her sister. It is also possible that the RBFOX1 deletion is associated with an increased risk of seizure disorder with variable expressivity.