Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication

Abstract

Treatment‐resistant epilepsy is among the most serious complications of cardiofaciocutaneous syndrome (CFCS), a rare disorder caused by germline variants in the RAS‐MAPK signaling pathway. This study analyzed the clinical characteristics of epilepsy and response to anti‐seizure medications (ASMs) in a multinational CFCS cohort. A caregiver survey provided data regarding seizure history, use of ASMs and other treatment approaches, adverse effects, caregiver perception of treatment response, and neurological disease burden impact among individuals with CFCS. Results from 138 survey responses were quantitatively analyzed in conjunction with molecular genetic results and neurological records. The disease burden impact of CFCS was higher among individuals with epilepsy (n = 74/138), especially those with more severe seizure presentation. Oxcarbazepine, a sodium‐channel blocker, had the best seizure control profile with relatively infrequent adverse effects. The most commonly prescribed ASM, levetiracetam, demonstrated comparatively poor seizure control. ASM efficacy was generally similar for individuals with BRAF and MAP2K1 gene variants. The high proportion of patients with CFCS who experienced poor seizure control despite use of multiple ASMs highlights a substantial unmet treatment need. Prospective study of ASM efficacy and clinical trials of therapies to attenuate RAS‐MAPK signaling may improve avenues for clinical management.

Long-term clinical course of adult-onset refractory epilepsy in cardiofaciocutaneous syndrome with a pathogenic MAP2K1 variant: a case report

“…In particular, the patient’s seizures responded well to LCM, which has a minimal risk of drug interactions, and is safe and effective. This finding is consistent with a recent publication showing relatively high efficacy scores of sodium-channel blockers in CFC ( Kenney-Jung et al, 2024 ). Our patient experienced DIHS, an adverse drug reaction commonly associated with aromatic antiseizure drugs in Japanese patients, such as PB and carbamazepine ( Hama et al, 2022 ).…”