Restless leg syndrome (RLS) is a neurological disease characterized by irresistible urge to move one's body to stop uncomfortable sensations. It is also considered a sleep disorder because it can severely diminish overall quality of sleep, and thus effect daily activities.
The most consistent finding with RLS patients is an iron deficiency, but it is not the main cause of the symptoms. Studies using an MRI have shown decreased iron in the substantia nigra, part of the brain where dopamine-producing cells reside. There is still little known on how iron is regulated by different cells in the brain.
Since dopamine stimulating drugs have shown improvement in RLS symptoms, studies have been performed to compare the dopamenergic pathway of affected and healthy patients. The studies showed that severe cases of RLS had lower dopamine levels and less severe cases had normal looking dopamine producing cells. This would suggest that there might be a defect somewhere in the pathway of dopamine system.
There are several genes that are associated with increased risk of developing RLS some point in the future. Studies have shown that MEIS1, BTBD9, LBXCOR1 and MAP2K5 have a significant association in RLS patients. Since RLS has multiple influencing genes it is hard to determine what effect the absence or damage of each one has on the overall symptoms.
GWAS and RLS Edit
Restless leg syndrome follows an autosomal dominant pattern of inheritance affecting 5-10% of the population. Genome wide association studies have linked multiple genes to RLS symptoms, including the BTBD9 gene which was the main gene that 23andMe focused on in their report. BTBD9 is located on the short arm of chromosome 6. Other studies have shown that the SNP rs3923809, located in the non coding region of BTBD9 greatly influences the phenotype of restless leg syndrome. One study from the New England Journal of Medicine compared number of limb movements per hour to two different allelic snp's, rs3923809 A and G. The A allele correlated to a higher number of limb movements while G showed lower.
23andMe report Edit
The genome report showed that John Burke is heterozygous (AG) for the rs3923809 snp. Although 70-80% of Europeans carry the A allele only 10% show the phenotype. Since John Burke has the AG genotype he is considered to have a decreased risk of developing RLS.
1. Raizen, D. M., and M. N. Wu. "Genome-Wide Association Studies of Sleep Disorders." Chest (2011): 446-52. Print.
3. Stockman, J.a. "A Genetic Risk Factor for Periodic Limb Movements in Sleep." Yearbook of Pediatrics: 337-38. Print.