The phenotypic spectrum of YWHAG-related epilepsy: From mild febrile seizures to severe developmental delay and epileptic encephalopathy

This study aimed to investigate the phenotypic spectrum and genotype–phenotype correlation in YWHAG-related epilepsy. We performed a comprehensive analysis of clinical data from 15 patients in our Chinese cohort and compared these findings with data from 40 patients documented in previous studies. Our investigation identified seven novel and five unique genetic variations in our cohort.

The results indicate that the majority of affected children experienced their first seizure within the first 2 years of life, with generalized tonic–clonic seizures (GTCS) and myoclonic seizures being the predominant seizure types observed. The phenotypic spectrum of YWHAG-related epilepsy ranged from mild febrile seizures plus to severe developmental and epileptic encephalopathy.

Significantly, most variants were localized within the highly conserved triad (HCT) domain Arg132-Arg57-Tyr133 of the YWHAG, whereas variations occurring outside this domain were generally associated with milder phenotype. Seizure control was achieved in seven children, primarily through the administration of valproate and levetiracetam.