Restless legs Syndrome

Restless legs Syndrome (RLS, OMIM*102300) is one of the most common neurological disorders with an age-dependent prevalence of up to 5-10% in Europe and North America.  RLS is characterized by an irresistible urge to move the legs accompanied by disagreeable, painful sensations in the lower limbs at night. Moving the affected legs or walking leads to prompt but only temporary relief. As a consequence, patients suffer from severe insomnia resulting in an impairment of quality of life, physical, mental and social health. It is a lifelong disorder with progressive symptoms. About 30% of the affected require lifelong medication. RLS is a genetically complex trait with an interaction of genetic and environmental factors. Genetic risk variants were first identified by J. Winkelmann an her team in regions encoding the genes MEIS1, BTBD9, SKOR1/MAP2K5, PTPRD and TOX3. Rare and very rare variants of strong effect, which cannot be identified by means of GWAS due to their rarity, form an important component of the genetic spectrum. Further variants remain to be identified by means of large scale sequencing studies.

RLS is a fruitful trait for studying gene-environment interactions. RLS can occur as a comorbidity of specific environmental triggers including uremia and pregnancy, and can completely disappear after these environmental conditions resolve (e.g. via kidney transplantation or parturition). However, the causative mechanisms linking genome, environment, and disease manifestation remain to be discovered. Our research objectives are to identify genetic and environmental factors, gain understanding of the biological basis, develop cellular assays and animal models, and identify new approaches for prevention and treatment.