Genetic association studies have not produced consistent results in restless legs syndrome (RLS).

To conduct a systematic review on genetic association studies in RLS to highlight the common gene variants and ethnic differences.

We conducted Pubmed, Embase, and Cochrane search using terms “Genetic association studies” and “restless legs syndrome” for candidate gene-based studies. Out of the initial 43 studies, 18 case control studies (from 2012 to 2022) were included. Thirteen studies including 10794 Caucasian subjects (4984 RLS cases and 5810 controls) and five studies involving 2009 Asian subjects (796 RLS cases and 1213 controls) were tabulated and analyzed. In addition, three Genome-Wide Association Studies (GWAS) in Asians and Europeans/Caucasians were included for comparisons.

In the Asian population, gene variants in BST1, SNCA Rep1, IL1B, BTBD9, and MAP2K5/SKOR1 increased the risk of RLS (odds ratio range 1.2–2.8). In Caucasian populations, examples of variants that were associated with an increased risk of RLS (odds ratio range 1.1–1.9) include those in GABRR3 TOX3, ADH1B, HMOX1, GLO1, DCDC2C, BTBD9, SKOR1, and SETBP1. Based on the meta-analysis of GWAS studies, the rs9390170 variant in UTRN gene was identified to be a novel genetic marker for RLS in Asian cohorts, whereas rs113851554 in MEIS1 gene was a strong genetic factor among the >20 identified gene variants for RLS in Caucasian populations.

Our systemic review demonstrates that multiple genetic variants modulate risk of RLS in Caucasians (such as MEIS1 BTBD9, MAP2K5) and in Asians (such as BTBD9, MAP2K5, and UTRN).

Polyfarmacy and unjustified use of high dosages of medicaments represent an unmet need in modern psychiatry. Therefore, tidal medication review of hospitalized geriatric patients is an essential step of the disease management as it can be often of vital importance and, as illustrated by current case, can exhibit a tremendeus impact on their quality of life.

A case rapport on geriatric patient with iatrogenic damage due to ultra high dosage of ropinirole as a treatment for restless legs syndrome

Authors of current paper address pharmacodynamic particularities of psychopharmaca and their reasonable choice in context to RLS

A clinical case of a 72 y.o. patient, known with chronic minor depressive symptomes over the past decades. Since few years he did not take any medicaion, except ropinirol for RLS. Because of the worsening of RLS symptomes, he decided on his own to increase the dose of ropinirol up to 12 mg/day. Two moths later he has been admitted to the psychiatric ward with major depression symptomes, suicidal plans, insomnia and profound edema of his both lower legs.

Current case demonstrates that high dose of ropinirole led to tremendous decrease of quality of life of the patient, and pushed him towards concrete suicidal plans. We advocate for careful assessing of the dose of every drug used; avoiding of polypharmacy by any means and for keeping in consideration that the majority of psychopharmaca leads to deterioration of RLS symptoms through modulation of dopamine pathways.

No significant relationships.

Using as a starting point a clinical case, the authors performed a literature review to clarify the relationship between visual hallucinations and treatment with ropinirole.

Analysis of the patient's clinical process and brief review of the latest available literature on the subject, published in PubMed/Medline databases.

Female patient, 89 years old, without psychiatric illness, brought to the emergency room by visual hallucinations, in the past 3 days “I see red, blue and green spots and roses on your sweater and a lot of flowers on that lady's blouse”sic. She recognised them as unreal (pseudo hallucinations) “no, nothing is there. It's from my eyes. I am fine of the head”sic. She has a personal history of glaucoma for decades, and restless legs syndrome for about 1 year, medicated with ropinirole. Adherence to therapeutic has been explored and it was found that she has been increasing, progressively and by its own initiative, the dose of ropinirole. She claims to be currently taking two pills of 8 mg twice daily (the recommended daily dose is 24 mg).

Studies indicate that the incidence of hallucinations during the treatment of RLS with ropinirole is less than 1%, which can be justified by its high affinity for D3 receivers compared to D2 receivers. However, it is also known that the over-stimulation of dopamine receptors (by overdose or rapid titration) can cause hallucinations, which may have been the cause of the patient's clinical condition. This clinical case also allows to alert for the importance of excluding organic causes in the diagnosis of visual hallucinations.

The incidence of restless legs syndrome (RLS) is presumed to be higher among people with schizophrenia who take antipsychotic medication, most of which blocks the dopamine D2 receptor. The purpose of this study was to determine whether the G-protein β3 subunit (GNB3) C825T polymorphism is associated with antipsychotic-induced RLS in schizophrenia.

We examined 178 Korean patients with schizophrenia. All of the subjects were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group and the International Restless Legs Scale. Genotyping was performed for the C825T polymorphism in the GNB3 gene.

The genotype distribution did not differ significantly between antipsychotic-induced RLS patients and patients who had no-RLS symptoms (χ2 = 4.30, p = 0.116). The genotypes of the C825T single-nucleotide polymorphism (SNP) were classified into two groups: C+ (CC and CT genotypes) and C– (TT genotype). The presence of the C allele (C+) was associated with an increased likelihood of RLS (χ2 = 4.14, p = 0.042; odds ratio = 2.56, 95% confidence interval = 1.02–6.47).

These results suggest that the GNB3 C825T SNP is associated with RLS in schizophrenia. However, confirming this association requires future larger scale studies in which the effects of medication are strictly controlled.