Genetics Testing for Restless Leg Syndrome

Restless leg syndrome (RLS) is a neurological disorder that causes strange painful sensations in the legs when the patient tries to rest or lie down. According to the National Institutes of Health, an estimated 12 million Americans may have RLS, although it varies widely in severity. Many cases are thought to be inherited; while there's no genetic test to identify the disorder at present, researchers have made some progress in identifying genes that may be linked to the disease.

Effects

• When patients with RLS try to rest or relax, they experience peculiar unpleasant sensations in their legs that seem to diminish when they start to move their legs again. Patients with severe RLS often find it difficult to get to sleep since they have trouble lying down and staying still. While RLS sometimes originates with iron deficiency or peripheral neuropathy, it often has no clear cause. According to the Mayo Clinic, nearly half of those diagnosed have a family history of the disorder, implying that genetics is a likely factor in predisposing patients to the disease.

Features

• At present, doctors diagnose RLS based on clinical examination and medical history rather than genetic tests, since the genetics of the disease are still poorly understood and thus, no genetic tests are available yet. Scientists researching RLS hope, however, that elucidating the molecular basis of the disease could help develop a genetic test and even more importantly, develop treatments.

Types

• Scientists research the genetics of RLS by studying families in which the disorder is passed down from generation to generation. These studies have typically found that RLS is inherited in an autosomal dominant fashion, meaning that the gene(s) involved are not on a sex chromosome and that a child only needs to inherit one copy of the culprit gene(s) in order to develop RLS. One study, however, found a possible genetic candidate using an autosomal recessive model, meaning a child would have to inherit two copies of this gene (one from each parent) to have the disease.

Theories/Speculation

• A study published in the journal Nature Genetics in 2007 identified three genes that may be linked to RLS using statistical associations. Other studies have have located different regions of the genome that may be involved as well. Given that multiple genetic variants may be involved, the genetics of RLS might be more difficult to unravel than simpler disorders like sickle cell anemia, which involves a single gene.

Potential

• While scientists are reasonably confident that genetics plays a major role in RLS, it's still not clear which genes cause RLS or how they do so. Ongoing research aims at confirming the links or associations uncovered by past studies and determining how they cause the disease. The dramatic drop in the cost of genome sequencing over the past five years could provide scientists with more data, not only for RLS but also for many other disorders. If scientists can conclusively ascertain which genetic variants are responsible, it may become possible to test for RLS in the future.