We reviewed the results of testing in patients from the West of Scotland attending adult epilepsy clinics with MRI-negative drug-resistant epilepsies or epilepsies with co-morbid intellectual disability,
Methods 45 eligible (>18y) cases were referred for testing. Clinicians completed a structured electronic clinical referral proforma to aid variant interpretation. Cases were tested on a custom-designed 104-gene panel focusing on disorders for which MRI would not provide a diagnosis. Variants were classified using UK Association of Clinical Genetic Science Guidelines. Variants of uncertain significance (VUS), likely pathogenic, and definitely pathogenic variants were discussed by a multidisciplinary team. Diagnostic variants were confirmed by Sanger sequencing.
Results Among 45 cases, likely pathogenic and pathogenic (diagnostic) variants were identified in 8 (18%), with VUS in 10 (22%). Pathogenic variants were identified in the following genes; GAMT, CHRNB2, SCN2A, PCDH19, PRRT2, SLC2A1, SCARB2, and SBTX1B.
All cases with abnormal results or VUS were offered referral to a Genetic Epilepsy Clinic for counselling. Genetic findings altered therapy in several cases: some with VUS became seizure-free with targeted changes in treatment. Determination of clinical significance was sometimes helped by further familial testing.
Conclusion Genetic testing is an essential tool in the management of adult patients with drug-resistant epilepsy, particularly those with childhood onset and/or accompanying learning difficulties. Abnormalities can be expected in approximately 40% using these criteria, which can aid both management and family counselling.
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