Genetic testing in children enrolled in epilepsy surgery program. A real-life study
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
37812946
DOI
10.1016/j.ejpn.2023.09.009
PII: S1090-3798(23)00154-X
Knihovny.cz E-resources
- Keywords
- Focal drug-resistant epilepsy, Genetic testing, Malformations of cortical development, Paediatric epilepsy surgery, mTOR,
- MeSH
- Child MeSH
- Epilepsies, Partial * complications MeSH
- Epilepsy * genetics surgery complications MeSH
- Fibroblast Growth Factors genetics MeSH
- Genetic Testing MeSH
- Humans MeSH
- Malformations of Cortical Development * genetics MeSH
- Prospective Studies MeSH
- GTPase-Activating Proteins genetics MeSH
- Nerve Tissue Proteins genetics MeSH
- Drug Resistant Epilepsy * diagnosis genetics surgery MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- FGF12 protein, human MeSH Browser
- Fibroblast Growth Factors MeSH
- NPRL3 protein, human MeSH Browser
- GTPase-Activating Proteins MeSH
- Nerve Tissue Proteins MeSH
- SZT2 protein, human MeSH Browser
OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.
References provided by Crossref.org
