While the cause is generally unknown, it is believed to be caused by changes in the nerve transmitter dopamine resulting in an abnormal use of iron by the brain.<unk>  is often due to iron deficiency (low total body iron status). Other associated conditions may include end-stage kidney disease and hemodialysis, folate deficiency, magnesium deficiency, sleep apnea, diabetes, peripheral neuropathy, Parkinson's disease, and certain autoimmune diseases, such as multiple sclerosis.<unk>  can worsen in pregnancy, possibly due to elevated estrogen levels. Use of alcohol, nicotine products, and caffeine may be associated with<unk> . A 2014 study from the American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with<unk>  symptom severity in untreated patients. ADHD An association has been observed between attention deficit hyperactivity disorder (ADHD) and<unk>  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)<unk> , and up to 26% of people with<unk>  had confirmed ADHD or symptoms of the condition. Medications Certain medications may cause or worsen<unk> , 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<unk>  from discontinuing benzodiazepine tranquilizers or sleeping pills * alcohol withdrawal can also cause<unk>  and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics * opioid withdrawal is associated with causing and worsening<unk>  Both primary and secondary<unk>  can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing<unk> . 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<unk>  could cause the conditions, or medication used to treat a condition could cause<unk> . Genetics More than 60% of cases of<unk>  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<unk>  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<unk> . * This locus maps to chromosome 2p and was found in three related families from population isolated in South Tyrol. * The sixth locus is located on chromosome 16p12.1 and was discovered by Levchenko et al. in 2008. Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to<unk> . Their role in<unk>  pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated with<unk> . There is also some evidence that periodic limb movements in sleep (PLMS) are associated with on chromosome 6p21.2, MEIS1, MAP2K5/SKOR1, and PTPRD. The presence of a positive family history suggests that there may be a genetic involvement in the etiology of<unk> .
Restless legs syndrome
Akathisia
Parkinsonism
Insomnia
Cancer-related fatigue
Gigantism
Bruxism
Lonomia