Thursday, May 26, 2016

Blog #70: Genetic Testing Can Impact Epilepsy Care

     More and more genes are now known to cause epilepsy. When I was training as a neurology resident in 1970, most epilepsy conditions were thought to be “idiopathic,” i.e., of unknown cause. The origin of most neurological conditions was of unknown cause at that time. We just treated the symptoms of stroke, epilepsy, dementia, etc. However, in 2016, the cause of so many of those conditions can now be identified as definite gene aberrations on our chromosomes. Scientists have sometimes even been able to alter certain genes that cause diseases and improve or even cure the condition.

     Dr. Annapurna Poduri, MD, MPH, Associate Professor of Neurology at Harvard Medical School, reviewed the latest on genetic epilepsy at the 69th Annual Meeting of the American Epilepsy Society in Philadelphia. Her comments were reviewed in the May 2016 Neurology Reviews. She explained that there are a small but growing number of genes associated with specific treatment recommendations which can allow for precision-medicine-in-epilepsy-treatment. Altered genes have been identified, to date, in 3 percent of genetic epilepsy. An abnormal gene should now be considered as the possible cause in people whose brain scans and medical histories give no clue as to why their epilepsy developed, in contrast to the many people with epilepsy whose brain scans show scars, abnormal blood vessels, tumors, infections, and other changes known to be associated with epilepsy. The SCN1A gene is important in epilepsy. SCN1A-related seizure disorders are inherited in an autosomal dominant manner. For example, half of the offspring of one parent who passed down that gene has a high risk of developing epilepsy, but the risk of developing seizures is not definite since genetic effects are not always manifest even if the abnormal gene is present. Genetic counselors can be very valuable in evaluating for genetic diseases and in interpreting genetic tests. Other epilepsy genes are also being discovered, such as the DNM1 geneit has been associated with “infantile spasms” and with the Lennox-Gastaut Syndrome.

     Some genes are associated with a benign course of epilepsy. If genetic testing reveals this gene is present, that person can be encouraged that the course of his epilepsy will probably be benign and easily controlled by anticonvulsant medications. This knowledge can provide families and their physicians a degree of diagnostic certainty and reassurance. If the SCN1A-mutated gene in Dravet syndrome is identified, doctors would then know to avoid Lamotrigine (Lamictal) and Phenytoin (Dilantin) because these commonly used antiepileptic medications can worsen these seizures. The GR1N2A gene mutation can cause changes that worsen seizures, but adding Memantine, a drug used in Alzheimer’s Dementia, dramatically reduced the seizures in a child in whom this gene was identified.

     Dr. Poduri concluded that neurologists should pursue genetic testing to give their patients the advantages of the latest genetic discoveries. Better-informed patients can now explore genetic testing with their neurologist to see if it would be appropriate for them.

Lance Fogan, M.D. is Clinical Professor of Neurology at the David Geffen School of Medicine at UCLA. “DINGS” is his first novel. It is a mother’s dramatic story that teaches epilepsy, now available in eBook, audiobook and soft cover editions.