What Causes Restless Legs Syndrome?

The exact cause of restless legs syndrome is not known. The idiopathic or primary form of the disease seems to occur sporadically for unknown reasons. A family history of RLS is reported in many of these patients, suggesting a genetic component to the disease. Documented cases of parent-to-child transmission suggest that, in some familial cases, RLS may be inherited. In 2001, a French-Canadian group reported on a study of 25 family members, 14 of whom had RLS. The researchers suggest an autosomal recessive mode of inheritance in this family, with several candidate locations on chromosome 12 (Desautels A, Turecki G, Montplaisir J, et al. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am J Hum Genet. 2001;69:1266-1270).

Secondary (or symptomatic) RLS occurs as a result of an underlying medical condition or in association with the use of certain drugs. For example, some conditions that may cause secondary RLS include kidney failure, low levels of iron, anemia, pregnancy, and peripheral neuropathy.

The symptoms of RLS may begin at any stage of life, including childhood, adolescence, or adulthood; however, the disease is more common with increasing age. Children with RLS are often misdiagnosed with "growing pains," anxiety disorders, or attention-deficit hyperactivity disorder (ADHD). Forty percent of those diagnosed with RLS during adulthood report having experienced symptoms before the age of 20 years. RLS affects both males and females; however, females often seem to be more severely affected and thus may be more likely to seek medical attention leading to a diagnosis of RLS. About 42% of patients initially experience symptoms on one side of the body, and approximately 25% report unusual sensations and motor restlessness in their arms. A large majority (about 94%) experience associated sleep disturbance.

Is it possible that another medical problem may cause RLS?
Before recommending or prescribing any treatments, physicians assess patients to exclude any underlying disorders, conditions, or other factors that may be responsible for causing or aggravating their RLS. Secondary causes may be suspected when RLS symptoms are brief or have recently become more severe.

Symptomatic restless legs syndrome may occur secondary to iron deficiency, anemia, folate deficiency, uremia, thyroid problems, diabetes, or peripheral neuropathy. In such cases, appropriate treatment of the underlying condition may eliminate or alleviate RLS symptoms. Such treatments may include the use of iron supplements for iron deficiency, medications that lower blood sugar levels for underlying diabetes mellitus, etc. Appropriate supplementation with B vitamins, vitamin C, vitamin E, folate, or magnesium may help ease symptoms even if a specific deficiency has not been determined.

Are there medications that may cause secondary RLS?
The use of certain prescription or over-the-counter medications may cause or aggravate restless legs syndrome. Therefore, before recommending or prescribing any specific treatments, physicians may ask for detailed information about the patient's current regimen of medications. If physicians suspect that specific over-the-counter medications are contributing to the occurrence of RLS, they may suggest the use of alternative medications. If they suspect that certain necessary prescription medications are causing or exacerbating RLS symptoms, physicians may work in coordination with a patient's other physicians to ensure appropriate, comprehensive treatment of any disorders or conditions that are present. The potentially offending medication may be replaced with another drug.

Medications that may cause or aggravate RLS symptoms include many antinausea drugs, such as Compazine® or Reglan®; certain medications that are administered to help prevent or control seizures, such as phenytoin; droperidol; particular antipsychotic drugs that produce tranquilizing effects, such as haloperidol and phenothiazine derivatives; and some cold and allergy medications. In addition, some rare instances have been reported where individuals who take certain drugs to treat depression (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs]) may experience some improvement in RLS symptoms; however, for the most part, such medications typically aggravate the symptoms of RLS.

	What is Happening to Produce RLS Symptoms?