What is the pathogenesis of restless legs syndrome (RLS)?

Updated: Feb 22, 2017
  • Author: Ali M Bozorg, MD; Chief Editor: Selim R Benbadis, MD  more...
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The pathogenesis of RLS is unclear. [2, 10, 11, 12] Currently, the most widely accepted mechanism involves a genetic component, along with abnormalities in the central subcortical dopamine pathways and impaired iron homeostasis. [13, 14]

When centrally acting dopamine receptor antagonists are administered to patients with the syndrome, symptoms are reactivated. Results of single-photon emission computed tomography (SPECT) have suggested a deficiency of dopamine D2 receptors. Iron homeostasis abnormalities have been implicated through cerebrospinal fluid (CSF) iron profile measures.

In addition, investigators have shown an increased severity of RLS with decreasing availability of serotonin transporter in the brainstem, which supports the hypothesis that increasing serotonin transmission in the brain may exacerbate RLS. [15]

RLS can also be genetic and run in families. [16] Various chromosomes have been implicated so far, including 12q, 14q, 9p, 20p, 4q, and 17p, in autosomal dominant and recessive fashion. [13]

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