Premium
Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families
Author(s) -
Winkelmann Juliane,
MullerMyhsok Bertram,
Wittchen HansUlrich,
Hock Bettina,
Prager Muriel,
Pfister Hildegard,
Strohle Andreas,
Eisensehr Ilonka,
Dichgans Martin,
Gasser Thomas,
Trenkwalder Claudia
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10282
Subject(s) - penetrance , phenocopy , restless legs syndrome , allele , disease , inheritance (genetic algorithm) , age of onset , family history , genetics , demography , medicine , psychology , biology , gene , psychiatry , phenotype , neurology , sociology
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 the families. Two hundred thirty‐eight RLS patients, 537 first‐degree relatives, and 133 spouses were interviewed. Two groups of families were stratified: mean age at onset up to 30 years of age (Group A) and older than 30 years (Group B; p < 0.005). In Group A, segregation analysis strongly favored a single major gene acting autosomal dominant with a multifactorial component. Parameter estimates were 0.003 for the allele frequency, 1.0 for the penetrance, and 0.005 for the phenocopy rate. In Group B, no evidence for a major gene could be elucidated. The segregation pattern found in our families argues for an autosomal allele acting dominantly in RLS families with an early age at onset of symptoms and suggests that RLS is a causative heterogeneous disease.