Family Study of Restless Legs Syndrome in Quebec, Canada

Abstract

To fully ascertain the familial aggregation of restless legs syndrome (RLS) and to characterize the clinical features of familial RLS (fRLS) cases. Design: A case series survey with a high response rate. Setting: Academic research center. Participants: Consecutive RLS probands (n = 249) were followed up in a specialized sleep center for 15 years. A total of 671 cases of fRLS met the current standard diagnostic criteria, including 192 probands characterized using multidimensional clinical assessments and 479 affected family members assessed by their responses to a structured questionnaire telephone diagnostic interview. Main Outcome Measures: Sibling and offspring relative risk ratio and clinical and genetic features of patients with fRLS and families. Results: Our data showed that RLS aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6 (95% confidence interval, 2.8-4.4), and an offspring relative risk of 1.8 (1.0-2.7). Familial RLS is a chronic disorder with a mean (SD) disease duration of 24(16) years and a wide range of age of onset (mean [SD], 28[15] years), with most family members having early-onset disease but mild to moderate RLS symptoms. Our clinical data also indicated that fRLS is more prominent among women who also had increased incidence of anemia/iron deficiency, arthritis, and number of pregnancies. Pregnancy-related RLS seems to be a characteristic feature of fRLS, and afflicted women tend to have a much younger age of onset. Conclusions: Restless legs syndrome significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease.

Heredity of Restless Legs Syndrome in a Pregnant Population

“…One family member (V-4) had no RLS symptoms after childbirth, and the other (V-2) reported RLS symptoms became chronic after childbirth. Xiong et al (2010) found that twice the amount of women had familial RLS compared to men (447 vs. 224) and that the three main associated medical conditions for women with familial RLS were anemia, arthritis, and pregnancy.…”

“…Family history of RLS in 60% to 77% of patients suggests a genetic link (Winkelmann et al, 2002;Xiong et al, 2010). Humans have 22 chromosome pairs plus two sex chromosomes.…”

“…No statistically significant differences in RLS prevalence were found related to the number of pregnancies beyond the first (Pantaleo et al, 2010). Xiong et al (2010) defined women with pregnancy related RLS as probands for whom the RLS symptoms appeared for the first time or were aggravated during pregnancy; pregnancyunrelated RLS was defined as RLS symptoms appearing well after pregnancy or remaining unchanged during pregnancy (Xiong et al). Although these researchers found women who were classified as pregnancy related RLS had more children compared to pregnancy unrelated RLS group, the degree of difference between the two groups was only one pregnancy.…”

Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

“…Moreover, inheritance was found to be related to late-onset RLS and secondary RLS (Winkelmann et al, 2000; Xiong et al, 2010; Yang et al, 2011). A study among 249 Canadian RLS patients found a family history existed in 77.1% of them while the rest 22.9% were sporadic (Yang et al, 2011).…”

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

“…In a familial study in a French Canadian population, siblings of an RLS patient had 3.6 times the risk of themselves having RLS, and an offspring, 1.8 times (Xiong et al, 2010). For early-onset RLS patients, Allen et al also reported a greater risk for RLS among the patients’ first-degree relatives compared to the first-degree relatives of late-onset RLS patients (23.6% v. 10.1%).…”