Pathogenic autosomal copy number variations were found in about 11% of epilepsy patients with comorbidities and 12.7% when possibly pathogenic variations were included, in a genetic study of over 1,000 patients in eight European epilepsy centers.
Subjects with nonneurological comorbidities, particularly dysmorphism, were more than four times as likely to carry a pathogenic copy number variation (CNV), a repeat in the genetic code. When seizures are associated with dysmorphism, intellectual disability (ID), and other comorbidities, “there is a higher probability of identifying a pathogenic CNV than in epilepsy alone,” said investigators led by Antonietta Coppola, PhD, a clinical research associate at the University of Naples Federico II Epilepsy Centre, in Italy.
“Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection,” they said.
She and her team are among many researchers unraveling the role of genetics in epilepsy. It’s estimated that up to 70% of cases have a genetic component, especially when diagnosed in childhood. Studies are proving that genetic anomalies – including CNVs – lead to specific and particularly devastating epileptic phenotypes (Epilepsia. 2019 Mar 13. doi: 10.1111/epi.14683).
The main driver of genetic testing for now seems to be diagnostic, to get a better idea of exactly what’s going on in particularly tough cases, but there might also be treatment implications. Whatever the case, it’s becoming important to test “for CNVs in patients with epilepsy and associated comorbidities,” the investigators said.
They pulled together CNV data from 1,097 patients with epilepsy and comorbid features including, among others, ID; autism; dysmorphic features; structural brain abnormalities; multidrug resistance; and psychiatric symptoms.
Overall, 120 (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 (1.7%) carried at least one autosomal CNV classified as possibly pathogenic.