Restless Legs Syndrome

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common neurological disorder characterized by an irresistible urge to move the legs, often accompanied by uncomfortable sensations.^[1] These symptoms typically occur during periods of rest or inactivity, particularly in the evening or at night, and are temporarily relieved by movement such as walking. ^[1] The prevalence of RLS can be as high as 10% in the general population, increasing with age, especially in individuals over 65 years old. ^[1]

As a sensorimotor disorder, RLS has a complex biological basis believed to involve both genetic and environmental factors. ^[1] Genetic research, particularly through genome-wide association studies (GWAS), has identified several susceptibility loci. Known genetic variants associated with RLS are found in regions containing genes such as MEIS1, BTBD9, PTPRD, and MAP2K5/SKOR1. ^[1] Further studies have uncovered novel susceptibility loci on chromosomes 2p14 and 16q12.1, expanding the understanding of the genetic architecture underlying RLS. ^[1] These genetic insights point towards pathways that may be involved in the disorder’s development.

The clinical relevance of RLS stems from its significant impact on daily life. The uncomfortable sensations and the compelling urge to move often lead to substantial sleep disturbances, including difficulty falling asleep and staying asleep. ^[1] Consequently, individuals with RLS frequently experience reduced daytime functioning, fatigue, and impaired overall quality of life. ^[1]

Beyond individual suffering, the chronic nature of RLS and its widespread effects on sleep and daily activities contribute to a considerable burden on public health. The disorder can affect productivity, mental health, and social interactions, highlighting the social importance of accurate diagnosis and effective management strategies to improve patient outcomes and societal well-being.

Limitations

Understanding the genetic underpinnings of Restless Legs Syndrome (RLS) through genome-wide association studies (GWAS) is subject to several inherent limitations that influence the interpretation and generalizability of findings. These challenges span methodological design, the nature of the disease phenotype, and the broader context of genetic and environmental influences.

Methodological and Statistical Challenges

Genetic association studies for complex traits like RLS necessitate large sample sizes to reliably detect genetic variants that exert small individual effects. Despite efforts to combine discovery and replication cohorts, individual subsamples within these studies often exhibit variable statistical power, which can lead to inconsistencies where associations are confirmed in some cohorts but only yield nominally significant results in others ^[1]. This variability in replication can make it challenging to ascertain the robustness of initial findings and may suggest that some reported associations could be subject to effect-size inflation or represent false positives if not consistently validated across diverse and adequately powered cohorts^[2]. While joint analysis across multiple cohorts can enhance statistical power and is considered more efficient than relying solely on replication-based analyses ^[3], this approach also highlights the inherent difficulties in achieving consistent, independent replication for every identified locus.

Phenotypic Heterogeneity and Diagnostic Nuances

The diagnosis of Restless Legs Syndrome relies on subjective patient descriptions of uncomfortable sensations and an irresistible urge to move the lower limbs, symptoms that typically emerge during periods of rest and are alleviated by movement^[1]. This reliance on self-reported symptoms introduces a degree of phenotypic heterogeneity, as the interpretation, severity, and specific manifestations of these sensations can vary considerably among individuals. Such subjective diagnostic criteria can lead to potential misclassification of cases and controls, thereby attenuating true genetic signals and complicating the precise identification of genetic variants directly contributing to RLS. Consequently, the observed genetic associations might reflect a broader clinical presentation rather than a tightly defined biological subtype of the syndrome.

Generalizability and Unexplored Genetic Contributions

A significant limitation of many large-scale genetic studies, including those for RLS, is their predominant focus on populations of European ancestry ^[1]. This demographic skew restricts the generalizability of findings to other ancestral groups, where differences in genetic architecture, allele frequencies, and environmental exposures could lead to distinct genetic risk factors or effect sizes. Moreover, the genetic variants currently identified by GWAS typically explain only a fraction of the estimated heritability for RLS, a phenomenon often referred to as “missing heritability.” This suggests that a substantial portion of RLS susceptibility may be attributable to rarer genetic variants, structural genomic variations, epigenetic modifications, or complex interactions between genes and environmental factors that are not fully captured by current study designs. A comprehensive understanding of RLS etiology will necessitate expanding research to diverse global populations and integrating a wider array of genetic and environmental data.

Variants

Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs, often accompanied by uncomfortable sensations that typically worsen during periods of rest and in the evening or night^[1]. Genetic factors play a significant role in RLS susceptibility, with genome-wide association studies (GWAS) identifying several key loci. Among these, variants in MEIS1, BTBD9, PTPRD, and MAP2K5 have been consistently linked to an increased risk of RLS ^[1]. For instance, the MEIS1 gene, which encodes a transcription factor involved in neuronal development, features variants like rs2300478 that have shown strong associations with RLS risk ^[1]. Other MEIS1 variants, such as rs113851554 , may influence the expression or function of this critical developmental gene, potentially affecting neuronal pathways relevant to RLS pathogenesis. Similarly, BTBD9 (BTB/POZ domain-containing protein 9) is associated with RLS, with variants like rs4714163 , rs61192259 , and rs6920488 potentially impacting iron homeostasis or dopaminergic signaling, both of which are implicated in the disorder.

The PTPRD gene (Protein Tyrosine Phosphatase Receptor Type Delta) encodes a neuronal receptor-type protein tyrosine phosphatase involved in synapse formation and neuronal signaling. Several variants within PTPRD, including rs34602324 , rs6477358 , and rs10758996 , have been identified as risk factors for RLS, suggesting that altered neuronal connectivity or signal transduction may contribute to the condition ^[4]. Another gene, MAP2K5 (Mitogen-Activated Protein Kinase Kinase 5), is part of a signaling cascade that regulates cell growth, differentiation, and stress responses. Variants such as rs868036 , rs868037 , and rs4776967 in MAP2K5 are associated with RLS, potentially by affecting neuronal survival, repair, or the function of dopaminergic neurons, which are central to RLS pathophysiology ^[1]. These genetic insights highlight the complex interplay of developmental, signaling, and neuronal processes in the manifestation of RLS.

Beyond these established loci, recent research has uncovered novel susceptibility regions. An intergenic region on chromosome 2p14, encompassing genes like LINC01812 and FBXL12P1, has been identified as a new RLS locus, with the variant rs6747972 showing significant association ^[1]. This region may harbor regulatory elements influencing nearby genes involved in neuronal function. Similarly, a locus on chromosome 16q12.1, in proximity to TOX3 and the non-coding RNA BC034767, was also recognized as a novel RLS susceptibility factor, with rs3104767 being a key variant ^[1]. While CASC16(Cancer Susceptibility Candidate 16) is located in this region, specific variants likers3104769 , rs45544231 , and rs3112626 may influence its expression or the expression of neighboring genes, potentially contributing to RLS through mechanisms yet to be fully elucidated, possibly related to neuronal activity or circadian rhythm regulation.

Further genetic studies continue to expand our understanding of RLS etiology, pointing to additional candidate genes and variants that may contribute to the disorder’s complex inheritance pattern. Variants in genes like LINC01677 and MTATP6P14 (such as rs12044119 , rs10458531 , rs12046503 ) or UNCX and MICALL2 (including rs113230729 , rs112716420 , rs2361717 ) are under investigation for their potential roles in neuronal development, mitochondrial function, or cytoskeletal dynamics, which can indirectly impact nervous system health and RLS symptoms. Similarly, CCDC148 (Coiled-Coil Domain Containing 148) variants like rs77276698 and rs113330028 , and LMO1 and STK33 variants such as rs10769894 and rs7102266 , may affect cellular processes critical for neuronal excitability or repair. The identification of these numerous genetic loci underscores that RLS is a polygenic disorder, where multiple genetic variations, often with small individual effects, collectively increase an individual’s susceptibility to the condition, influencing factors from neurotransmitter balance to neuronal development and maintenance ^[1].

Key Variants

RS ID	Gene	Related Traits
rs868036 rs868037 rs4776967	MAP2K5	restless legs syndrome
rs113851554 rs2300478	MEIS1	circadian rhythm, excessive daytime sleepiness measurement, sleep duration trait, insomnia measurement insomnia measurement restless legs syndrome physical activity measurement insomnia
rs3104769 rs45544231 rs3112626	CASC16	restless legs syndrome
rs4714163 rs61192259 rs6920488	BTBD9	restless legs syndrome
rs1820987 rs1820989 rs6747972	LINC01812 - FBXL12P1	insomnia restless legs syndrome
rs12044119 rs10458531 rs12046503	LINC01677 - MTATP6P14	restless legs syndrome
rs34602324 rs6477358 rs10758996	PTPRD	restless legs syndrome
rs113230729 rs112716420 rs2361717	UNCX - MICALL2	restless legs syndrome
rs77276698 rs113330028	CCDC148	insomnia restless legs syndrome
rs10769894 rs7102266	LMO1 - STK33	restless legs syndrome

Classification, Definition, and Terminology

Defining Restless Legs Syndrome

Restless Legs Syndrome (RLS) is precisely defined as a sensorimotor disorder characterized by uncomfortable sensations and an irresistible urge to move the lower limbs^[1]. This operational definition highlights both the sensory discomfort and the motor imperative that are central to the condition. The symptoms distinctively emerge during periods of rest and relaxation, particularly in the evening or at night, and are characteristically relieved, at least temporarily, by movement such as walking or stretching ^[1]. This unique pattern of symptom presentation and relief is a hallmark of RLS, distinguishing it from other conditions involving leg discomfort.

The conceptual framework for RLS positions it as a common neurological disorder, impacting a significant portion of the general population, with its prevalence increasing with age, reaching up to 10% in individuals over 65 years old ^[1]. Beyond the immediate sensations and urge to move, individuals with RLS frequently experience significant sleep disturbances. These sleep disruptions can lead to considerable consequences, including reduced daytime functioning and overall diminished quality of life ^[1].

Diagnostic Criteria and Clinical Assessment

The diagnosis of Restless Legs Syndrome relies on a specific set of clinical criteria that have been developed and standardized to ensure consistent identification of the disorder. These diagnostic criteria, along with special considerations and epidemiological aspects, were comprehensively reported by a consensus from a dedicated workshop held at the National Institutes of Health^[5]. This framework provides a precise and systematic approach for clinicians to assess symptoms, differentiate RLS from other conditions, and establish a definitive diagnosis.

While the detailed thresholds and cut-off values for each criterion are not provided, the existence of such a robust diagnostic report underscores the importance of a structured measurement approach in clinical practice and research. This standardized methodology is crucial for accurate patient identification, facilitating appropriate management strategies, and supporting consistent research into the underlying mechanisms and genetic predispositions of RLS.

Terminology and Disease Classification

The established nomenclature for this condition is “Restless Legs Syndrome,” often abbreviated as RLS. This key term is universally recognized in medical and research contexts, providing a clear and unambiguous label for the disorder^[1]. Within broader nosological systems, RLS is classified as both a “sensorimotor disorder” and a “neurological disorder” ^[1].

This dual classification emphasizes its complex nature, involving both abnormal sensory experiences and involuntary motor responses, and places it within the realm of nervous system pathologies. Understanding RLS through this classification helps differentiate it from conditions that are purely sensory or purely motor, reflecting its unique pathophysiology and guiding clinical investigation and therapeutic approaches.

Signs and Symptoms

Characteristic Sensorimotor Symptoms

Restless Legs Syndrome (RLS) is primarily characterized as a distinctive sensorimotor disorder, manifesting through an often irresistible and unpleasant urge to move the lower limbs, accompanied by uncomfortable sensations^[1]. These sensations are typically described as creeping, pulling, tingling, or aching, and they are almost exclusively localized to the legs, though they can rarely affect other body parts. A hallmark feature is that these symptoms are initiated or exacerbated during periods of inactivity or rest, such as sitting or lying down, and they characteristically occur in the evening or throughout the night ^[1]. The defining relief mechanism for these discomforts is movement, with walking or active leg movements providing temporary but significant alleviation of symptoms ^[1].

Temporal Patterns, Variability, and Assessment

The presentation of RLS symptoms follows distinct temporal patterns, predominantly affecting individuals during their inactive hours, particularly in the evening or night, and during periods of rest ^[1]. This nocturnal predominance and the relief gained from movement are crucial for subjective assessment, as patients typically report these patterns in detail for diagnosis. The disorder’s prevalence demonstrates significant variability, notably increasing with age; it affects up to 10% of the general population, with a higher incidence observed in individuals over 65 years old ^[1]. This age-dependent pattern highlights RLS as a common neurological disorder, with its manifestation and impact varying across the lifespan and among individuals.

Associated Impairments and Diagnostic Significance

The unique constellation of symptoms—uncomfortable leg sensations, an irresistible urge to move, onset during rest, and relief with activity—holds significant diagnostic value in identifying RLS ^[1]. The presence of these specific features, particularly their temporal pattern and response to movement, allows for clinical recognition of the disorder. A major clinical correlation and consequence of these nocturnal symptoms is significant sleep disturbance, which in turn leads to reduced daytime functioning for affected individuals ^[1]. Therefore, assessing the impact on sleep quality and daily activities is crucial in understanding the overall severity and burden of the syndrome.

Causes of Restless Legs Syndrome

Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by uncomfortable sensations and an irresistible urge to move the lower limbs, particularly during periods of rest in the evening or at night^[1]. While the precise etiology of RLS is complex, a combination of genetic and physiological factors is understood to contribute to its development and progression.

Genetic Predisposition

RLS exhibits a notable genetic component, with family studies suggesting an inherited predisposition. Genome-wide association studies (GWAS) have been instrumental in identifying specific genetic susceptibility loci that contribute to the disorder’s development. These include well-established common variants in genes such as MEIS1, BTBD9, PTPRD, and MAP2K5/SKOR1 ^[1]. Further research has uncovered novel risk loci on chromosomes 2p14 and 16q12.1, reinforcing the understanding of RLS as a complex trait influenced by multiple genetic factors ^[1]. This polygenic architecture indicates that an individual’s cumulative genetic profile plays a significant role in their overall susceptibility to RLS.

Age-Related Influences

The prevalence of Restless Legs Syndrome demonstrates a distinct age-dependent pattern, with a substantial increase observed in older populations. Specifically, studies indicate that up to 10% of individuals in the general population aged 65 years and above are affected by RLS^[1]. This heightened prevalence in later life suggests that age-related physiological changes may contribute to the onset or exacerbation of RLS symptoms. While the precise biological mechanisms driving this age-related increase are complex and require further elucidation, age stands out as a critical demographic factor influencing the expression and progression of the syndrome.

Biological Background

Restless Legs Syndrome (RLS) is a complex sensorimotor disorder characterized by uncomfortable sensations and an irresistible urge to move the lower limbs, primarily occurring during periods of rest in the evening or at night. The biological mechanisms underlying RLS involve a combination of genetic predispositions, disruptions in neurological pathways, and systemic consequences that significantly impact quality of life. Understanding these intricate biological aspects is crucial for comprehending the condition’s onset and progression.

Clinical Characteristics and Neurological Basis

Restless Legs Syndrome manifests as a distinct sensorimotor disorder, where individuals experience unpleasant sensations within their lower limbs, accompanied by a compelling urge to move them. These symptoms are uniquely tied to periods of inactivity or rest, typically intensifying in the evening or during the night, and find temporary relief through movement such as walking or stretching. This pattern suggests a fundamental disruption in the neurological circuits responsible for processing sensory information and controlling motor responses, particularly those active during transitions between wakefulness and sleep. The disorder’s age-dependent prevalence, affecting up to 10% of the population over 65 years of age, also hints at potential age-related changes influencing these neurobiological processes.

Genetic Predisposition and Loci Identification

Genetic factors play a significant role in an individual’s susceptibility to Restless Legs Syndrome. Genome-Wide Association Studies (GWAS) have been instrumental in uncovering specific genomic regions associated with an increased risk of developing the disorder. For instance, novel susceptibility loci have been identified on chromosomes 2p14 and 16q12.1^[1]. These discoveries build upon earlier GWAS findings that pinpointed common genetic variants in three other distinct genomic regions, reinforcing the polygenic nature of RLS ^[1]. Furthermore, research has also identified a specific genetic risk factor linked to periodic limb movements in sleep, a condition frequently co-occurring with RLS, highlighting overlapping genetic influences on sleep-related motor disturbances ^[6].

Molecular and Cellular Implications of Genetic Findings

The identification of specific genetic susceptibility loci for Restless Legs Syndrome strongly suggests that the molecular and cellular pathways underlying neurological function are disrupted in affected individuals. These identified genomic regions likely harbor genes or regulatory elements that influence critical cellular processes, such as neuronal signaling pathways, neurotransmitter metabolism, or the overall function of specific cell types within the central nervous system. While the precise molecular mechanisms remain under investigation, the genetic findings imply altered gene expression patterns and regulatory networks that contribute to the characteristic sensorimotor symptoms. Comprehensive research efforts, including expression analysis, are actively exploring how these genetic variants translate into functional changes at the cellular level^[1].

Systemic Consequences and Homeostatic Disruptions

The core symptoms of Restless Legs Syndrome, characterized by their onset during rest and relief through movement, signify a profound disruption in the body’s homeostatic balance regulating sensory perception and motor control. This imbalance primarily impacts the lower limbs but has broader systemic consequences. A major outcome is significant sleep disturbance, as the symptoms interfere with sleep initiation and maintenance, leading to chronic sleep deprivation. These sleep disruptions, in turn, contribute to reduced daytime functioning, impacting cognitive performance, mood, and overall quality of life. The interplay between genetic predisposition, neurological dysfunction, and environmental factors likely contributes to the age-dependent increase in prevalence, suggesting a complex interaction that compromises homeostatic regulation over time.

Pathways and Mechanisms

Genetic Architecture and Gene Regulatory Mechanisms

Restless Legs Syndrome (RLS) is a complex sensorimotor disorder with a significant genetic component, as evidenced by genome-wide association studies (GWAS). These studies have identified novel susceptibility loci for RLS on chromosomes 2p14 and 16q12.1, in addition to common variants found in three other genomic regions^[1]. These genetic variations are hypothesized to influence gene regulation, impacting the expression levels or function of proteins critical for neurological processes. Such regulatory mechanisms, including potential alterations in transcription factor activity or feedback loops, contribute to the underlying pathway dysregulation observed in RLS.

Neurobiological Signaling and Sensorimotor Control

The characteristic symptoms of RLS, such as uncomfortable sensations and an irresistible urge to move the lower limbs, indicate a disruption in neurobiological signaling pathways responsible for sensorimotor control ^[1]. While the precise molecular interactions are complex, the identified genetic susceptibility likely perturbs specific signaling cascades, affecting receptor activation and intracellular communication within neural circuits. This dysregulation can alter neuronal excitability and the integration of sensory and motor information, particularly during rest, which is a hallmark of RLS symptom manifestation.

Inter-Pathway Crosstalk and Network Interactions

The genetic underpinnings of complex disorders like RLS often involve intricate network interactions and pathway crosstalk. Although specific interactions for RLS are not detailed, genome-wide analyses in related neurological conditions, such as Tourette’s syndrome and obsessive-compulsive disorder, suggest complex genetic relationships ^[7]. Similarly, studies on narcolepsy implicate antigen presentation to T cells ^[8]. These findings illustrate that RLS susceptibility loci may operate within a broader network, where genetic variations can influence multiple interconnected biological pathways, contributing to the disorder’s emergent properties through systemic interactions.

Hierarchical Regulation and Emergent Disease Properties

The identified genetic susceptibility loci for RLS contribute to a hierarchical regulation of biological systems, where molecular alterations at the gene level manifest as complex, emergent properties of the disease. The collective impact of genetic variants on gene expression and signaling pathways ultimately shapes the RLS phenotype. This systems-level integration implies that the uncomfortable sensations and motor urges arise from a cascade of molecular events, where the dysregulation within specific pathways, influenced by genetic predispositions, culminates in the observed sensorimotor disorder.

Clinical Relevance

Restless legs syndrome (RLS) is a prevalent sensorimotor neurological disorder characterized by uncomfortable sensations and an irresistible urge to move the lower limbs, typically occurring during rest in the evening or at night, with temporary relief provided by movement^[1]. Its age-dependent prevalence, affecting up to 10% of the population over 65 years, underscores its significant impact on public health ^[1]. Understanding the clinical relevance of RLS is critical for accurate diagnosis, effective management, and improving patient outcomes.

Genetic Predisposition and Risk Stratification

RLS is a common sensorimotor disorder with an age-dependent prevalence, affecting up to 10% of the population over 65 ^[1]. Genome-wide association studies have identified several susceptibility loci, including novel findings on 2p14 and 16q12.1, alongside previously known loci like MEIS1, BTBD9, PTPRD, and MAP2K5/SKOR1 ^[1]. These genetic insights are fundamental for risk stratification, enabling the identification of individuals with a higher genetic predisposition, which may inform future personalized medicine strategies and targeted prevention efforts. The varying relevance of these risk loci across different populations underscores the complex genetic architecture and the potential for individualized risk assessments ^[1].

Diagnostic Utility and Prognostic Value

The clinical relevance of RLS diagnosis stems from its characteristic presentation: uncomfortable sensations and an urge to move in the lower limbs, predominantly during rest in the evening or at night, with temporary relief upon movement ^[1]. While genetic markers are not yet routine diagnostic tools, understanding the genetic landscape of RLS could enhance diagnostic accuracy, especially in ambiguous cases or for distinguishing primary RLS. Furthermore, the age-dependent increase in prevalence suggests a progressive nature, highlighting the prognostic importance of early identification to anticipate potential long-term implications and disease progression^[1].

Therapeutic Strategies and Associated Complications

Informed treatment selection for RLS currently relies on symptom severity and impact on quality of life, but future therapeutic strategies may be refined by a deeper understanding of the implicated genetic pathways. Monitoring strategies are crucial to assess treatment response and manage the primary symptoms, as well as the significant associated complications. A key complication of RLS is the concomitant sleep disturbances, which directly lead to reduced daytime functioning, impacting patients’ overall well-being and productivity ^[1]. Addressing these sleep-related issues is an integral part of comprehensive patient care, aiming to mitigate the broader impact of the syndrome beyond just limb sensations.

Frequently Asked Questions About Restless Legs Syndrome

These questions address the most important and specific aspects of restless legs syndrome based on current genetic research.

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1. My parent has restless legs. Will I definitely get it too?

While RLS has a strong genetic component and your risk might be higher, it’s not a definite certainty. Studies have identified several genetic variants, like those in MEIS1 and BTBD9, that increase susceptibility. However, environmental factors also play a role, meaning genetics contribute to risk but don’t guarantee the condition.

2. Does my restless legs syndrome just get worse as I get older?

The prevalence of RLS is known to increase with age, especially in individuals over 65 years old. This suggests that while you might have a genetic predisposition, age-related factors can influence the onset or progression of your symptoms over time.

3. Why am I always so tired during the day with restless legs?

Your restless legs symptoms often make it very difficult to fall asleep and stay asleep at night. This chronic sleep disturbance leads to significant daytime fatigue, reduced functioning, and a lower overall quality of life, even if you feel you’ve been in bed for enough hours.

4. My RLS symptoms feel different from my friend’s. Is mine still real?

Absolutely, your experience is real. RLS diagnosis relies on subjective descriptions, meaning the specific sensations and their severity can vary quite a lot between individuals. This “phenotypic heterogeneity” is common, and your symptoms are valid even if they differ from others.

5. I’m not European. Does my background change my RLS risk?

Many large-scale genetic studies for RLS have predominantly focused on populations of European ancestry. This limitation means that genetic risk factors and their impact might differ in other ancestral groups, and the current findings might not fully generalize to your specific background. More diverse research is needed.

6. Why is it so hard for doctors to pinpoint the exact cause of my RLS?

RLS has a complex biological basis involving both genetic and environmental factors. While genes like MEIS1 and BTBD9 are known to contribute, they only explain a fraction of the risk. There are likely many other rare genetic variants, epigenetic factors, or complex gene-environment interactions not yet fully understood.

7. My restless legs make it hard to concentrate at work. Is that a common problem?

Yes, it’s a very common problem. The sleep disturbances caused by RLS often lead to reduced daytime functioning, fatigue, and impaired concentration. This can significantly affect your productivity, mental health, and social interactions, placing a considerable burden on your daily life.

8. Could a DNA test tell me if I’m likely to get restless legs?

Genetic studies have identified specific variants, such as those in or near MEIS1, BTBD9, PTPRD, and MAP2K5, that are associated with an increased risk of RLS. A DNA test could identify if you carry some of these known risk variants. However, RLS is complex, so it wouldn’t offer a definitive “yes” or “no” prediction, as other factors are involved.

9. My sibling doesn’t have RLS, but I do. Why the difference if it’s genetic?

Even with a genetic predisposition, RLS is influenced by a mix of genetic and environmental factors. You and your sibling might have inherited different combinations of risk variants, or your unique environmental exposures and lifestyle choices could have played a role in why the condition manifests in you and not in them.

10. Can my daily habits or environment affect my restless legs?

Yes, RLS is understood to involve both genetic and environmental factors in its development. While the article doesn’t detail specific environmental triggers, it acknowledges their role alongside your genetic predisposition. Paying attention to your overall health and lifestyle is always beneficial.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Winkelmann J, et al. “Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.”PLoS Genet, vol. 7, no. 7, 2011, e1002171.

[2] Tsai, F.J., et al. “Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.”PLoS One, vol. 6, no. 2, 2011, p. e16858.

[3] Skol, A.D., et al. “Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies.” Nat Genet, vol. 38, 2006, pp. 209–213.

[4] Schormair B, et al. “PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.”Nat Genet, vol. 40, 2008, pp. 946-948.

[5] Allen, R.P., et al. “Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.”Sleep Med, vol. 4, 2003.

[6] Stefansson, H, et al. “A genetic risk factor for periodic limb movements in sleep.” N Engl J Med, vol. 357, no. 6, 2007, pp. 639–647.

[7] Yu, D., et al. “Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette’s syndrome and OCD.” Am J Psychiatry, vol. 172, no. 1, 2015, pp. 84-93.

[8] Faraco, J., et al. “ImmunoChip study implicates antigen presentation to T cells in narcolepsy.” PLoS Genet, vol. 9, no. 3, 2013, p. e1003270.