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
gene—it 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.
