A rare genetic association of one silent (ADGRV1) and other unquiet (MED13L) mutation: A case report

Two genes likely to cause epilepsy, one silent and the other manifesting in a patient with drug-resistant epilepsy, can be quite unusual. Herein, we described the case of a 2-year-old girl who presented with predominant language development delay, facial dysmorphism, and refractory epilepsy with normal neuroimaging and metabolic profiles, which prompted us to consider genetic etiology. Her genetic test revealed two novel likely pathogenic mutations, in Mediator complex subunit 13-like (MED13L) and adhesion G protein-coupled receptor V1 (ADGRV1). Sanger sequencing of her parents revealed an ADGRV1 variant in her unaffected mother. The child had a phenotypic match with the MED13L genotype. However, only a few cases of MED13L have reported refractory epilepsy and the corresponding mutation was missense. To the best of our knowledge, this is the first case of frameshift mutation in MED13L presenting with refractory epilepsy. Although the child harbored two likely pathogenic mutations, the one inherited from her mother in ADGRV1 did not manifest, whereas the frameshift mutation in MED13L had expressed as refractory epilepsy, which has not been described hitherto.