Authors :
Presenting Author: Dorottya Kacsoh, – University of Central Florida College of Medicine
Omer Abdul Hamid, MD – Nemours Children's Hospital
Rationale:
Variants in the DEPDC5 gene cause a broad spectrum of focal epilepsies, most commonly familial focal epilepsy with variable foci. Most foci are in the frontal or temporal lobes, but involvement of the parietal and occipital lobes is not uncommon. This disorder is inherited in an autosomal dominant pattern with variable penetrance and many affected family members have areas of focal cortical dysplasia that vary from individual to individual. Interictal EEGs may be normal. Seizures may begin at any age, and intellect is generally preserved. We present a case of a teenaged female with focal cortical dysplasia found to have a novel variant in the DEPDC5 gene. Methods:
A teenage girl with a history of debilitating migraines, severe Tourette syndrome, ADHD, anxiety, and depression presented for new-onset seizures. Seizures were characterized by versive head turning to the left with a high frequency tremor, tongue biting, unresponsiveness, and a post-ictal period. She had a family history of epilepsy in a maternal uncle and cousin. Topiramate was started for migraine prophylaxis with the dual function of being anti-seizure medications. Her seizure frequency decreased, and oxcarbazepine was added to as adjuvant therapy. Results:
A routine EEG was normal. MRI of the brain showed an area of focal cortical dysplasia in the right frontal lobe subcortical white matter. Genetic testing showed a variant of uncertain significance in DEPDC5, c.2006+2 T >G.Conclusions:
To the best of our knowledge, we describe a novel intronic variant in the DEPDC5 gene causing familial focal epilepsy with variable foci. This variant is likely to be pathogenic because it occurs in the context of a patient with epilepsy and focal cortical dysplasia. While intronic variants have been described, the majority of reported variants occur in the exome. This case reinforces the idea that intronic variants may also contribute to the development of DEPDC5-related epilepsy.
Funding: n/a