TY - JOUR
T1 - Epilepsy in cardiofaciocutaneous syndrome
T2 - Clinical burden and response to anti-seizure medication
AU - Kenney-Jung, Daniel L.
AU - Collazo-Lopez, Josue E.
AU - Rogers, Dante J.
AU - Shanley, Ryan
AU - Zatkalik, Abigail L.
AU - Whitmarsh, Ashley E.
AU - Roberts, Amy E.
AU - Zenker, Martin
AU - Pierpont, Elizabeth I.
N1 - Publisher Copyright:
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
KW - BRAF
KW - MAP2K1
KW - RASopathies
KW - seizures
KW - treatment
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U2 - 10.1002/ajmg.a.63428
DO - 10.1002/ajmg.a.63428
M3 - Article
C2 - 37827855
AN - SCOPUS:85173898949
SN - 1552-4825
VL - 194
SP - 301
EP - 310
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 2
ER -