Epilepsy - autosomal recessive disorder

Epilepsy

Epilepsy

Epilepsy affects approximately 1% of the population making it one of the most common neurological diseases. Epilepsy can strike at any time of life—from infancy to old age. While epilepsy varies widely in type and severity, all forms of this disorder are characterized by recurring seizures resulting from abnormal cell firing in the brain. In approximately 30% of cases, epilepsy is caused by such events as head trauma, tumor, stroke, or infection. In those cases for which there is no known cause, recent evidence suggests there may be genetic predisposition to developing the disease.

There are many forms of epilepsy—most are rare. But to date, at least twelve forms of epilepsy have been demonstrated to possess some genetic basis. For example, LaFora Disease (progressive myoclonic, type 2), a particularly aggressive epilepsy, is characterized in part by the presence of glycogen-like Lafora bodies in the brain. It is an autosomal recessive disorder that has been linked to mutation of the gene EPM2A, found on chromosome 6. This gene produces a phosphatase called laforin. The regulatory function of the phosphatase may be disrupted by mutation, leading to LaFora Disease. Some recent work suggests that laforin may be found in similar parts of the cell as glycogen synthase, a glycogen processing enzyme, and that the mutations may misplace laforin within the cell, leading indirectly to a loss of EPM2A function.

Much progress has been made in narrowing down regions of chromosomes associated with different forms of epilepsy. With this effort, scientists continue to expand the list of genes involved in seizure disorders. Animal models of epilepsy also contribute to our understanding of electrical brain disturbances. By focussing on the genetic basis for epilepsy, scientists hope to develop more effective anticonvulsive treatments and, possibly, gene replacement therapies for seizure disorders such as LaFora Disease.top link