ADHD
An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder. Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain. A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition. Medications
Certain medications may cause or worsen RLS, or cause it secondarily, including:
certain antiemetics (antidopaminergic ones)
certain antihistamines (especially the sedating, first generation H1 antihistamines often in over-the-counter cold medications)
many antidepressants (both older TCAs and newer SSRIs)
antipsychotics and certain anticonvulsants
a rebound effect of sedative-hypnotic drugs such as a benzodiazepine withdrawal syndrome from discontinuing benzodiazepine tranquilizers or sleeping pills
alcohol withdrawal can also cause restless legs syndrome and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics
opioid withdrawal is associated with causing and worsening RLSBoth primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS.
Genetics
More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra. Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine. Six genetic loci found by linkage are known and listed below. Other than the first one, all of the linkage loci were discovered using an autosomal dominant model of inheritance. The first genetic locus was discovered in one large French Canadian family and maps to chromosome 12q. This locus was discovered using an autosomal recessive inheritance model. Evidence for this locus was also found using a transmission disequilibrium test (TDT) in 12 Bavarian families. The second RLS locus maps to chromosome 14q and was discovered in one Italian family. Evidence for this locus was found in one French Canadian family. Also, an association study in a large sample 159 trios of European descent showed some evidence for this locus. This locus maps to chromosome 9p and was discovered in two unrelated American families. Evidence for this locus was also found by the TDT in a large Bavarian family, in which significant linkage to this locus was found. This locus maps to chromosome 20p and was discovered in a large French Canadian family with RLS. This locus maps to chromosome 2p and was found in three related families from population isolated in South Tyrol.