Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti-seizure medication.
Am J Med Genet A
; 194(2): 301-310, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-37827855
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ectodermal Dysplasia
/
Facies
/
Drug-Related Side Effects and Adverse Reactions
/
Epilepsy
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Failure to Thrive
/
Heart Defects, Congenital
Limits:
Humans
Language:
En
Journal:
Am J Med Genet A
Journal subject:
GENETICA MEDICA
Year:
2024
Document type:
Article
Affiliation country:
United States