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Session Schedule

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0:00:00
Introduction: The phenotypic clinical diversity of RLS
Diego Garcia-Borreguero (Spain)

0:32:20
Pediatric RLS phenotypes: Early onset and unique challenges
Gulcin Benbir Senel (Turkey)

1:00:05
Adult RLS phenotypes: Clinical variability in adulthood
Claudia Trenkwalder (Germany)

Genetic insights into RLS: Shared variants and comorbidities
Arthur Walters (United States)

Summary

Restless Legs Syndrome (RLS) encompasses a diverse spectrum of clinical presentations, each with unique implications for diagnosis, management, and research. This symposium will explore the proposed distinct phenotypes of RLS, highlighting shared genetic underpinnings, clinical manifestations, and treatment challenges. Experts in the field will discuss the current understanding of these phenotypes and identify areas for future research and therapeutic advancements.
The first presentation will provide a comprehensive overview of these diverse clinical profiles, setting the stage for deeper exploration in subsequent talks. It will highlight the variability in symptom frequency and severity, drawing on findings from recent clinical studies and patient-reported outcomes. Attendees will gain a foundational understanding of the phenotypic spectrum of RLS symptoms, equipping them with the knowledge to contextualize more specific discussions on subtypes, comorbidities, and management strategies. Also, the rationale for selection of different therapies across phenotypes will be outlined and discussed.
The second presentation will provide a detailed review of pediatric RLS phenotypes, drawing from contemporary literature to explore how RLS presents differently in children compared to adults. The talk will highlight the often subtle and atypical symptoms in children, including behavioral manifestations such as restlessness, inattention, or sleep resistance, which can mimic conditions like ADHD. The role of iron deficiency, developmental changes, and familial predisposition as key factors influencing pediatric RLS will be presented . Additionally, the overlap between RLS and other pediatric sleep disorders will be discussed, such as periodic limb movement disorder (PLMD), and the importance of early diagnosis to prevent long-term consequences on sleep and neurocognitive development.
The third speaker will provide a comprehensive review of adult RLS phenotypes, drawing from the latest literature to explore the variability in clinical presentations, relationship with insomnia, cardiovascular disorders, and mood disorders, among other comorbidities that contribute to symptom severity and progression. This talk with present the findings from adult RLS literature and discuss the implications for personalized diagnostic and therapeutic approaches in clinical practice.
Finally, the symposium will explore the genetic underpinnings of these associations, presenting findings from two innovative studies leveraging Genome-Wide Association Studies (GWAS) and Phenome-Wide Association Studies (PheWAS). The first study identifies 365 genetic variants associated with RLS, including significant overlap with hypertension, insomnia, ADHD, and circadian rhythm disturbances, providing insights into shared genetic susceptibilities. The second study extends these findings by replicating RLS associations for 84 variants and identifying additional links with conditions like thyroid disease, rheumatoid arthritis, and diabetes. Together, these studies demonstrate the utility of GWAS and PheWAS approaches in unraveling the genetic architecture of RLS and its frequent co-occurrence with other medical conditions. Attendees will gain a deeper understanding of how shared genetic pathways may inform future diagnostic and therapeutic strategies for RLS and its comorbidities.

Learning Objectives:

Upon completion of this CME activity, participants will be able to:
• Gain an understanding of the phenotypic spectrum of RLS symptoms, equipping them with the knowledge to contextualize more specific discussions on subtypes, comorbidities, and management
• Recognize that RLS manifests with unique presentations in pediatric populations. It will highlight the often subtle and atypical symptoms in children, including behavioral manifestations such as restlessness, inattention, or sleep resistance, which can mimic conditions like ADHD. It will emphasize the role of iron deficiency, developmental changes, and familial predisposition
• Demonstrate that RLS exhibits diverse phenotypes in adulthood, as influenced by age, gender, and environmental factors. The talk will provide a comprehensive review of RLS phenotypes, drawing from the latest literature to explore the variability in clinical presentations, relationship with insomnia, cardiovascular and mood disorders, and contribute to symptom severity and progression
• Describe findings from two studies on GWAS and PheWAS. While the first study identified 365 genetic variants associated with RLS, including significant overlap with hypertension, insomnia, ADHD, and circadian disturbances, the second replicated associations for 84 variants and identified additional links with thyroid disease, rheumatoid arthritis, and diabetes