Home > Medical Reference > Patient EducationServices at Maryland GeneralA complete list of inpatient and outpatient healthcare services at MGH.Restless legs syndrome and related disorders - CausesDescriptionAn in-depth report on the causes, diagnosis, treatment, and prevention of RLS.Alternative NamesEkbom's syndrome; Nocturnal leg cramps; Periodic limb movement disorder Causes:The main cause of restless legs syndrome (RLS) is unknown. Researchers are investigating neurologic (nervous system) problems that may arise either in the spinal cord or the brain. One current theory suggests that a deficiency in a brain chemical called dopamine causes restless legs syndrome. RLS may often have a genetic basis, particularly in those who develop it before age 40. When the condition occurs in older adults, it is most likely due to a neurological problem. The central nervous system is comprises the brain and spinal cord. The peripheral nervous system includes all peripheral nerves. ![]() Genetic FactorsPeople with restless legs syndrome (RLS) often have a family history of the disorder. Researchers have detected specific genetic locations or factors that might be responsible for this condition. Much of the research comes from studies of families with a strong history of RLS-related conditions. Researchers originally linked a location on chromosome 12 to RLS. They named this genetic marker RLS1. Since then, 4 more locations have been mapped on chromosomes 2, 9, 14, and 20. These genes are labeled RLS 2 through 5. Neurologic AbnormalitiesDopamine and Neurologic Abnormalities in the Brain. A variety of studies support the theory that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS. Dopamine and serotonin cause numerous nerve impulses that affect muscle movement. The effect is similar to what happens in Parkinson's disease. Moreover, drugs that increase dopamine levels treat both disorders. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose a person to Parkinson's later on. Neurologic Abnormalities in the Spine. Other research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. Researchers considered that such abnormalities were likely to start in nerve pathways in the lower spine. However, some patients with RLS have symptoms in the arms, indicating that the upper spine may also be involved. Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. So far, there is no evidence of a causal relationship. Deficiencies in Iron MetabolismIron deficiency, even at a level too mild to cause anemia, has been linked to restless legs syndrome (RLS) in some people. Studies suggest, in fact, that RLS in some people may be due to a problem with getting iron into cells that regulate dopamine in the brain. Some studies have reported RLS in 25 - 30% of people with low iron levels. Causes of Periodic Limb Movement DisorderThe cause or causes of periodic limb movement disorder (PLMD) are not clear. Some research suggests that it may be due to abnormalities in the autonomic nervous system, which regulates the involuntary actions of the smooth muscles, heart, and glands. Resources
ReferencesBayard M, Avonda T, Wadzinski, J. Restless Legs Syndrome.American Family Physician. 2008;78(2): 235-240. Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006 Jan;81(1):17-27. Claman DM; Redline S; Blackwell T, Ancoli-Israel S, Surovec S, Scott N, et al. Prevalence and correlates of periodic limb movements in older women. J Clin Sleep Med. 2006 Oct;2(4):438-445. Gamaldo CE, Earley CJ. Restless Legs Syndrome. Chest. 2006;130(5):1596-1604. Lohmann-Hedrich K, Neumann A, Kleensang A, et al. Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci? Neurology. 2008;70(9):686-694. Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep. 2007; 30(7): 866-71. Oertel WH, Benes H, Bodenschatz R, Peglau I, Warmuth R, Happe S, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology. 2006 Sep 26;67(6):1040-6. Ong KH, Tan HL, Tam LP, et al. Accuracy of serum transferrin receptor levels in the diagnosis of iron deficiency among hospital patients in a population with a high prevalence of thalassaemia trait. Int J Lab Hematol. 2008;30(6):487-493 Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. Sleep Med. 2006 Aug;7(5):407-17. Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005 Jul 1;28(7):891-8. Picchietti D. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics. 2007; 120(2): 253-66. Stefansson H, Rye DB, Hicks A, et al. A Genetic Risk Factor for Periodic Limb Movements in Sleep. N Engl J Med. 2007;357:639-47. Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034-9. Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet (in press). [cited in: Winkelmann J. Periodic Limb Movements in Sleep - Endophenotype for Restless Legs Syndrome? N Engl J Med. 2007; 357:703-05.
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