Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families

  title={Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families},
  author={Juliane Winkelmann and Bertram Muller-Myhsok and Hans-Ulrich Wittchen and Bettina Hock and Muriel Prager and Hildegard Pfister and A. Strohle and Ilonka Eisensehr and Martin Dichgans and Thomas Gasser and Claudia Trenkwalder},
  journal={Annals of Neurology},
A strong familial component of restless legs syndrome (RLS) is known. The objective of this study therefore was to investigate the likely mode of inheritance of RLS. RLS patients and their first‐degree relatives were investigated and classified in RLS affected and RLS nonaffected subjects. Assessments were based on direct, personal standardized diagnostic interviews. Complex segregation analysis was performed with the families stratified according to the mean age at onset of the disease within… 

Segregation Analysis of Restless Legs Syndrome: Possible Evidence for a Major Gene in a Family Study Using Blinded Diagnoses

The high rate of phenocopies matches known population frequencies and taken with significant residual familial effects and the lack of evidence for a major gene controlling age of onset, indicates that non-genetic causes of RLS may exist and RLS is a complex disorder.

Two pedigrees with restless legs syndrome in Brazil.

The symptoms, the sleep profiles and physiological parameters of two families in which several members present RLS/PLM, a prevalent sleep disorder affecting about 5 to 15% of the population and one that substantially impairs healthy sleep patterns are described.

Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features

The analysis supports the prevailing hypothesis that RLS is divided into earlier onset disease with a clear genetic component and later onset disease wich unclear etiology, and that one or more endophenotypes might exist within the disorder which could further characterize these subjects for future genetic studies.

Restless legs syndrome: Epidemiological and clinicogenetic study in a South Tyrolean population isolate

The absence of a suggestive linkage signal at the three known RLS susceptibility loci is indicative of further locus heterogeneity of this frequent disorder and encourages further studies to unveil the genetic causes of RLS.

Evidence for further genetic locus heterogeneity and confirmation of RLS‐1 in restless legs syndrome

Evidence for linkage on chromosome 12 supports the existence of RLS‐1 and provides evidence for the likelihood of further genetic locus heterogeneity of RLP, and further genome wide linkage analyses have the potential to identify additional RLS loci.

Genetics of restless legs syndrome: An update.

Genetics of restless legs syndrome.

  • J. Winkelmann
  • Biology
    Current neurology and neuroscience reports
  • 2008

Genetics of restless legs syndrome

Genome-wide association studies identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBOXCOR1 andMEIS1 and LBXCOR1 that have weak and moderate effects and increase the risk of developing RLS.

Genetics in restless legs syndrome.




Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients.

It is shown that patients with hereditary RLS may experience an earlier onset of the disease, compared to those of non-hereditary RLS, which was similar in both groups.

Studies of penetrance and anticipation in five autosomal‐dominant restless legs syndrome pedigrees

In two of the five analyzed pedigrees, there is statistical support for anticipation and variations in penetrance and anticipation suggest possible genetic heterogeneity.

Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome

This large German kindred of familial RLS with 20 affected and investigated members in four generations showed the variety of clinical RLS symptoms with decreasing age of onset in generations II‐IV, suggesting at least the possibility of anitcipation.

Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q.

These findings represent the first mapping of a locus conferring susceptibility to RLS, and positioning the RLS-predisposing gene in a 14.71-cM region between D 12S1044 and D12S78 is refined.

Multiple etiologies for Alzheimer disease are revealed by segregation analysis.

It is revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onsets groups, and the results suggest that the higher risk to females is not solely due to their increased longevity.

A questionnaire study of 138 patients with restless legs syndrome

A telephone survey of their symptomatology found that more than a third of the patients in each group experienced their first symptoms before the age of 20 and in the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering.

Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: A study of 133 patients diagnosed with new standard criteria

A strong relationship was found between these complaints and polysomnographic findings; increasing sleep latency and number of awakenings and decreasing sleep efficiency were associated with worsening symptoms.

Restless legs syndrome in monozygotic twins: Clinical correlates

Article abstract—To better understand genetic characteristics of restless legs syndrome (RLS) and identify nongenetic factors that may influence phenotype, the authors studied 12 identical twins in

Variable expressivity in familial restless legs syndrome.

It is concluded that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs Syndrome gene.