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

Winkelmann, Juliane; Müller‐Myhsok, Bertram; Wittchen, Hans‐Ulrich; Hock, B.; Prager, Muriel; Pfister, Hildegard; Ströhle, Andreas; Eisensehr, Ilonka; Dichgans, Martin; Gasser, Thomas; Trenkwalder, Claudia

doi:10.1002/ana.10282

Cited by 226 publications

(119 citation statements)

References 25 publications

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“…Although the data from this study are consistent with multiple genetic effects contributing to restless legs symptoms, other studies have suggested an autosomal dominant pattern of inheritance (Bonati et al, 2003;Winkelmann et al, 2002). Further, a locus mapping to chromosome 14q in a family with an autosomal dominant inheritance pattern has been identified (Bonati et al, 2003).…”

Section: Discussionsupporting

confidence: 79%

Genetic Influences in Self-Reported Symptoms of Obstructive Sleep Apnoea and Restless Legs: A Twin Study

et al. 2004

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Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.

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Section: Discussionsupporting

confidence: 79%

Genetic Influences in Self-Reported Symptoms of Obstructive Sleep Apnoea and Restless Legs: A Twin Study

et al. 2004

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“…Studies attempting to determine a possible mode of transmission further reflect the genetic heterogeneity of early--versus late--onset subtypes. The involvement of a major gene, with autosomal--dominant mode of transmission is evident for early--onset RLS only; while late--onset RLS appears to be compatible with a model of free transmission (Winkelmann et al 2002). In both cases, however, there is evidence for a role of a multifactorial component, with the possibility of other genetic and non--genetic factors A and B (see Winkelmann et al 2007, for a review).…”

Section: Restless Legs Syndrome (Rls): Rls Is Characterised By Unpleamentioning

confidence: 99%

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Barclay

Gregory

2013

Current Topics in Behavioral Neurosciences

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Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities.Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co--occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia, and emotional/ behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

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“…Five loci (12, 14, 9, 2, and 20 p) have already been described 13 . A recent article showed the association between a sequence variant in chromosome 6 p with PLM in distinct Icelandic and American cohorts of subjects with RLS and their families 14 . A simultaneous report by Winkelman 15 showed an association between the same sequence variant and two additional single nucleotide polymorphisms in German and Canadian cohorts with RLS.…”

Section: Periodic Limb Movement and Restless Legs Syndrome Geneticsmentioning

confidence: 99%

Spinal cord injury as a trigger to develop periodic leg movements during sleep: an evolutionary perspective

Telles

Alves

Chadi

2012

Arq. Neuro-Psiquiatr.

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Spinal cord injury as a trigger to develop periodic leg movements during sleep: an evolutionary perspectiveLesão medular como gatilho para desenvolver movimentos periódicos das pernas durante o sono: uma perspectiva evolutiva Susana Cristina Lerosa Telles, Rosana S. Cardoso Alves, Gerson ChadiThe periodic limb movement (PLM) disorder is characterized by periodic episodes of repetitive and highly stereotyped limb movements, which occur during sleep, and by clinical sleep disturbance that cannot be accounted for by another primary sleep disorder 1 . They consist of the big toe extension in combination with partial flexion of the ankle and, sometimes, hip (Fig 1). Similar movements can occur in the upper limbs. This occurrence in spinal cord injury (SCI) patients 2 (Fig 2) suggests the spinal origin of those movements, which could be due to the disruption of REM-related inhibitory spinal pathways, producing the disconnection or disinhibition of a spinal generator, which is a kind of local pacemaker 3 .Restless legs syndrome (RLS) is a sensorimotor disorder frequently related to PLM and was recently reported in SCI patients 2 . It is characterized by a complaint of a strong, nearly irresistible, urge to move the legs, which is made worse by rest (lying or sitting) and is at least partially and temporarily relieved by walking or moving the legs. The relief is usually immediate. The urge to move the legs worsens in the evening and at night 1 . Scientific reviews have addressed the probable central pattern generator (CPG) in SCI patients and its outcome to rehabilitation. We based this review on an evolutionary perspective of CPG development from invertebrates to mammals, in order to point to the probable CPG action in humans during PLM. ABSTRACTThe primary trigger to periodic limb movement (PLM) during sleep is still unknown. Its association with the restless legs syndrome (RLS) is established in humans and was reported in spinal cord injury (SCI) patients classified by the American Spinal Injury Association (ASIA) as A. Its pathogenesis has not been completely unraveled, though recent advances might enhance our knowledge about those malfunctions. PLM association with central pattern generator (CPG) is one of the possible pathologic mechanisms involved. This article reviewed the advances in PLM and RLS genetics, the evolution of CPG functioning, and the neurotransmitters involved in CPG, PLM and RLS. We have proposed that SCI might be a trigger to develop PLM.Key words: nocturnal myoclonus syndrome, restless legs syndrome, spinal cord regeneration. RESUMOO gatilho principal para o desenvolvimento de movimentos periódicos dos membros (MPM) durante o sono ainda é desconhecido. A associação entre o MPM e a síndrome das pernas inquietas (SPI) em seres humanos já foi previamente estabelecida e relatada em pacientes com lesão medular (LM), classificados pela American Spinal Injury Association (ASIA) como A. A patogênese do MPM não foi completamente desvendada, apesar de avanços recentes poderem ampliar o conhecimento sobre...

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

Cited by 226 publications

References 25 publications

Genetic Influences in Self-Reported Symptoms of Obstructive Sleep Apnoea and Restless Legs: A Twin Study

Genetic Influences in Self-Reported Symptoms of Obstructive Sleep Apnoea and Restless Legs: A Twin Study

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Spinal cord injury as a trigger to develop periodic leg movements during sleep: an evolutionary perspective

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