Diagnostic Yield of Genetic Testing in an Adult Epilepsy Clinic
Abstract number :
2.209
Submission category :
4. Clinical Epilepsy / 4A. Classification and Syndromes
Year :
2024
Submission ID :
638
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Beatriz Giraldez, MD – Hospital Universitario Fundación Jiménez Díaz. Madrid, Spain
Jose Serratosa, MD, PhD – Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
Rationale: The diagnostic yield and utility of genetic testing has been widely reported in pediatric and, to a lesser degree, in adult cohorts mainly in phenotype-focused or basic research-based studies. This study aimed to evaluate the diagnostic yield of genetic testing and the landscape of genetic epilepsies in adult patients attending the outpatient epilepsy clinic of a single tertiary hospital.
Methods: Retrospective review of genetic findings in adult patients attending our outpatient epilepsy clinic. Patients were referred for testing based on clinical suspicion of a genetic etiology. Patients with a pathogenic or likely pathogenic (P/LP) variant were identified.
Results:
Among 79 unrelated patients with epilepsy referred for genetic testing, 26 patients harbored a P/LP variant (33%). Twenty-two patients had intellectual disability that was moderate to severe in most. Mean age at time of genetic testing was 33 years (range 18-72 years). The most common genes found were CHD2 (4 patients), SCN1A (2 patients) and MECP2 (2 patients). Single patients harbored sequence changes in PACS1, SHANK3, EHMT1, ZEB2, NEXMIF9, TSC1, TSC2, CCM2, GABRB3, ANKRD11, KRIT1 and NFIB. Most of the P/LP variants were sequence changes identified by NGS (90%), whereas 10% were identified by direct Sanger sequencing. Gross deletions or duplications were detected in 5 patients, 4 of them were also identified by NGS and confirmed with CGH array. An intronic expansion in MARCH6 was identified in one patient by means of RP-PCR. We did not identify variants in many genes frequently reported in pediatric cohorts (i.e KCNQ2, SCN2A, STXBP1, CDKL5 or SCN8A). Only 8 of 26 patients had onset of epilepsy before 3 years of age.
Besides genetic counseling, the most common management changes were follow-up of comorbidities (11 patients) and introduction of specific antiseizure medications (3 patients).
Conclusions: In our cohort of adult ambulatory patients with suspected genetic epilepsy the diagnostic yield of genetic testing was consistent with previous studies (33%). The genetic landscape is different to that of pediatric cohorts. In a high proportion of patients a genetic diagnosis was useful to identify unsuspected comorbidities.
Funding: No funding.
Clinical Epilepsy