Genetics of epilepsy in clinical practice

Berkovic SF.  Genetics of epilepsy in clinical practice. Epilepsy Currents, Vol. 15, No. 4 (July/August) 2015 pp. 192–196

Abstract

Genetics should now be part of everyday clinical epilepsy practice. Good data exist to provide empiric risks based on epilepsy syndrome diagnosis. Investigation of the molecular basis of some epilepsies is now a practical clinical task and is of clear value to the patient and family. In some cases, specific therapeutic decisions can now be made based on genetic findings, and this scenario of precision therapy is likely to increase in the coming years,

From the article

Nihilistic views are sometimes expressed that finding a genetic cause does not alter management, and therefore genetic testing is unnecessary. If such views were ever defensible, they are certainly not now, for a number of reasons.

First, even if a condition is untreatable, patients and families nearly always want to know why the affliction has occurred. “Closure” of diagnosis is very important; it brings an end to the diagnostic odyssey, and families can stop searching for “answers” from multiple physicians or alternative medicine practitioners. This situation is particularly true when a previously healthy child develops an epileptic encephalopathy with refractory seizures and developmental regression. The parents may carry guilt, with a false belief that minor head knocks or vaccination caused the disorder—identifying the true cause can provide considerable consolation and assuage unfounded blame. Even in milder familial epilepsies, subjects generally wish to know.

Second, a specific genetic diagnosis avoids unnecessary testing with repeated blood tests, MRIs, invasive biopsies, pre-surgical workup, and even intracranial electrodes in the vain hope that a focal lesion or some other cause might be found in an unsolved case of epileptic encephalopathy. In turn, this allows families to focus on the problem and not be distracted by searching for the cause. A genetic diagnosis may provide useful prognostic information regarding the natural history of the disorder as large case series accumulate—this has already happened with Dravet syndrome and PCDH19-related epilepsy and will occur in time for rarer epilepsies. Families often derive benefit by meeting similarly affected families, either in person or online. Family-driven groups focused on a specific disorder have become a powerful force for aggregation of accessible information, for effective public advocacy, and for encouraging and driving research…

In addition to the general benefits of testing outlined above, there is a small but growing number of genetic diagnoses in which specific alterations in management are indicated. This may include the choice of conventional antiepileptic agents or the use of an alternative treatment…

Genetics is transforming clinical practice in epilepsy, especially in children. Useful clinical information can be provided to families, and a specific molecular diagnosis, where possible, adds greatly to the accuracy of the information. The promise of precision therapies is becoming a reality and may eventually become widely applicable.

http://www.epilepsycurrents.org/doi/pdf/10.5698/1535-7511-15.4.192