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Abstract
Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene–microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.
GLOSSARY
- CI=
- confidence interval;
- CRI=
- chronic renal insufficiency;
- CVD=
- cardiovascular disease;
- DSM-5=
- Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
- ESRD=
- end-stage renal disease;
- GWAS=
- genome-wide association studies;
- HR=
- hazard ratio;
- IDA=
- iron deficiency anemia;
- MS=
- multiple sclerosis;
- MSA=
- multiple system atrophy;
- OR=
- odds ratio;
- PD=
- Parkinson disease;
- PLMS=
- periodic limb movements in sleep;
- RLS=
- restless legs syndrome
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received July 23, 2015.
- Accepted in final form December 10, 2015.
- © 2016 American Academy of Neurology
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