Exploring Genetic Factors Influencing Periodic Limb Movement During Sleep

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Exploring Genetic Factors Influencing Periodic Limb Movement During Sleep

Date of Content: May 4, 2024
Written by: Jess Gayo
Reviewed by: Maarit Tiirikainen, PhD



Have you ever wondered why some people seem to toss and turn during sleep, their legs occasionally jerking involuntarily? This phenomenon known as periodic limb movement during sleep (PLMS) is characterized by repetitive, stereotypical limb movements during sleep. PLMS can disrupt sleep patterns and lead to restless sleep. Understanding its causes and implications is crucial for those greatly affected as it could lead to daytime fatigue due to interrupted sleep.

What is Periodic Limb Movement?

Periodic Limb Movement during Sleep (PLMS) is characterized by repetitive and involuntary movements, typically involving the legs, during sleep. These movements can range from subtle twitches to more pronounced jerking motions, disrupting the natural sleep pattern and leading to fragmented sleep architecture.

Individuals with certain genetic predispositions, as well as those with conditions such as restless legs syndrome (RLS), are often more susceptible to experiencing PLMS. Factors such as age, gender, and other underlying health conditions can also play a role in the prevalence of PLMS. 

Why Does Periodic Limb Movement Happen During Sleep?

Periodic limb movement during sleep (PLMS) occurs due to complex interactions between neurological and physiological factors. One primary mechanism involves disruptions in the brain’s control over muscle activity during sleep. 

Specifically, there appears to be an imbalance in neurotransmitters such as dopamine, which regulates muscle movement and coordination. Research suggests that deficiencies or dysregulation of dopamine pathways may contribute to the repetitive limb movements observed in PLMS.

Understanding the genetic and neurological underpinnings is crucial for both diagnosis and treatment, as it helps healthcare providers tailor interventions that address the root causes of PLMS, thereby improving sleep quality and overall well-being.

Is Periodic Limb Movement During Sleep Genetic?

In a 2015 study, researchers investigated genetic variations that are related to periodic limb movements during sleep (PLMS) in older adults. They analyzed data from 2,356 white male participants in the Osteoporotic Fractures in Men Sleep Study cohort.

They found that 61% of the men in the study had a high PLMS index, which refers to frequent limb movements during sleep. The study identified various SNPs that are significantly associated with PLMS. These include rs9357271 and rs3923809 in the BTBD9 gene, rs2300478 in the MEIS1, and rs1026732 in the MAP2K5/SKOR1 which strongly suggest that they were more likely to have a high PLMS index.

For instance, having the T allele of rs9357271 and A allele of rs3923809 in the BTBD9 gene increased the odds of a high PLMS index by 38%. Similarly, the G allele of rs1026732 in the MAP2K5/SKOR1 gene and the G allele of rs2300478 in the MEIS1 gene were associated with higher odds of PLMS. Even after adjusting for age, ancestry markers, and other PLMS risk factors, these associations remained significant.

Overall, this study confirms that genetic variations in BTBD9, MEIS1, and MAP2K5/SKOR1 play a role in the occurrence of periodic limb movements during sleep among elderly individuals. These findings contribute to understanding the genetic underpinnings of sleep disorders, potentially guiding future research and personalized treatment approaches for individuals affected by PLMS.

What Other Factors Can Influence Periodic Limb Movement During Sleep?

Periodic limb movement during sleep (PLMS) can be influenced by various environmental factors that interact with genetic predispositions. Understanding these factors is essential for individuals seeking to manage or mitigate PLMS symptoms. Here are the key environmental factors that can affect PLMS:

Sleep Environment and Habits

  • Sleep Position: Sleeping in certain positions, such as on the back (supine position), has been associated with increased PLMS activity. This may be due to changes in muscle tone and respiratory patterns that occur in different sleeping positions.
  • Sleep Quality: Poor sleep hygiene, including irregular sleep schedules, excessive caffeine or alcohol consumption before bed, and insufficient sleep, can exacerbate PLMS. Maintaining a regular sleep schedule and creating a conducive sleep environment can help reduce symptoms.

Medications and Substances

  • Dopamine Agonists and Antagonists: Medications that affect dopamine levels in the brain, such as certain antidepressants, antipsychotics, and anti-nausea drugs, can influence PLMS. These medications may either exacerbate or alleviate symptoms depending on their specific mechanisms of action.

Caffeine and Stimulants: Consumption of stimulants like caffeine close to bedtime can disrupt sleep patterns and potentially worsen PLMS symptoms. Managing the intake and timing of stimulants may help mitigate these effects.

Nutritional Factors

  • Iron Deficiency: Low levels of iron in the body have been associated with restless legs syndrome (RLS), which shares similarities with PLMS. Ensuring adequate dietary intake of iron-rich foods or supplements may help alleviate symptoms.
  • Magnesium and Calcium: Deficiencies in magnesium and calcium have also been implicated in RLS and may indirectly affect PLMS. Maintaining balanced levels of these minerals through diet or supplements could be beneficial.

Lifestyle Factors

  • Physical Activity: Regular physical activity has been shown to improve sleep quality and may help reduce PLMS symptoms. However, intense exercise close to bedtime should be avoided as it can temporarily increase arousal levels.
  • Stress and Mental Health: Stress and anxiety can disrupt sleep patterns and exacerbate PLMS. Practicing relaxation techniques, mindfulness, or seeking professional help for stress management may be beneficial.

Other Medical Conditions

  • Sleep Apnea: Individuals with obstructive sleep apnea are at higher risk for PLMS. Treating underlying sleep disorders, such as sleep apnea, may improve overall sleep quality and reduce PLMS episodes.
  • Neurological Disorders: Certain neurological conditions, such as Parkinson’s disease, may co-occur with PLMS due to overlapping mechanisms involving dopamine pathways.

Environmental Stimuli

  • Noise and Light: External stimuli like noise or bright lights can disrupt sleep and potentially trigger PLMS episodes. Creating a quiet, dark sleep environment can promote better sleep hygiene and reduce disturbances.

Understanding these environmental factors allows individuals to take proactive steps in managing PLMS. By addressing modifiable factors such as sleep habits, medication use, nutritional status, and stress levels, individuals can potentially reduce the frequency and severity of PLMS episodes. 

What are the Symptoms of Periodic Limb Movement During Sleep?

PLMS movements typically occur in cycles lasting 10 to 90 seconds, with episodes repeating every 20 to 40 seconds throughout the night. While individuals with PLMS are usually unaware of these movements, bed partners may notice jerking or twitching of the legs during sleep. Common symptoms of PLMS include:

  • Leg Movements: The hallmark symptom is rhythmic movements of the legs, often involving the ankles, knees, and hips. These movements can be subtle or forceful enough to cause brief awakenings.
  • Sleep Disturbance: PLMS can disrupt the individual’s sleep cycle, leading to fragmented sleep patterns. This results in daytime sleepiness, fatigue, and decreased alertness.
  • Restless Sensations: Some individuals may experience uncomfortable sensations in the legs while awake, particularly during periods of rest or inactivity (restless legs syndrome, which often co-occurs with PLMS).
  • Impact on Quality of Life: Chronic sleep disruption due to PLMS can affect overall well-being, contributing to mood disturbances and impaired cognitive function.
  • Associated Conditions: PLMS is commonly associated with other sleep disorders such as insomnia, sleep apnea, and restless legs syndrome. Understanding these associations is crucial for comprehensive management and treatment.

Recognizing these symptoms is important for timely diagnosis and management of PLMS. Seeking evaluation from a healthcare provider, particularly a sleep specialist, can help in developing a tailored management plan to improve sleep quality and overall health.

What is the Difference Between Restless Legs Syndrome and Periodic Limb Movement During Sleep?

Restless Leg Syndrome (RLS) and Periodic Limb Movement during Sleep (PLMS) are related yet distinct conditions involving involuntary movements and sensations in the legs.

Restless Legs Syndrome (RLS) is characterized by an irresistible urge to move the legs, often due to uncomfortable sensations such as tingling, crawling, or itching deep within the legs. These sensations typically worsen during periods of rest or inactivity, particularly in the evening or nighttime, and can temporarily improve with movement. 

RLS can significantly disrupt sleep and affect daily activities, contributing to impaired quality of life. While the exact cause of RLS isn’t fully understood, genetic factors play a significant role, with familial aggregation observed in many cases.

Periodic Limb Movement during Sleep (PLMS), on the other hand, involves involuntary repetitive limb movements during sleep, primarily affecting the legs. These movements occur in cycles lasting from a few seconds to several minutes, with episodes repeating multiple times throughout the night. 

Unlike RLS, individuals with PLMS are often unaware of these movements unless they cause them to wake up or disturb their sleep. PLMS is closely associated with sleep disorders such as insomnia and sleep apnea, and it can exacerbate daytime fatigue and sleepiness. Genetic predispositions and neurological factors contribute to the development of PLMS, and it often coexists with RLS.

While both conditions involve involuntary leg movements, RLS primarily affects wakefulness due to uncomfortable sensations, whereas PLMS manifests during sleep and disrupts sleep continuity.

Is Periodic Limb Movement During Sleep Permanent?

PLMS is not considered permanent in most cases. Research indicates that PLMS can fluctuate in intensity and may even resolve spontaneously in some individuals. However, for those with underlying conditions such as restless legs syndrome (RLS) or certain neurological disorders, PLMS may persist as a chronic condition requiring ongoing management.

Treatment options for PLMS focus on improving sleep quality and reducing the frequency of limb movements. Lifestyle modifications, medications, and addressing co-existing sleep disorders are commonly recommended strategies. Regular evaluation and management by a healthcare provider, particularly a sleep specialist, can help individuals effectively manage PLMS and minimize its impact on daily life.

What are Some Negative Effects of Periodic Limb Movement During Sleep?

Periodic limb movement during sleep (PLMS) can have several negative effects on both sleep quality and overall health:

  • Sleep Disruption: PLMS often leads to fragmented sleep, with frequent awakenings throughout the night due to involuntary limb movements. This disruption prevents individuals from achieving restorative sleep cycles, resulting in daytime sleepiness and fatigue.
  • Daytime Impairment: Chronic sleep disturbances caused by PLMS can impair daytime functioning, affecting cognitive abilities such as concentration, memory, and decision-making. This can impact work performance, academic success, and overall quality of life.
  • Increased Risk of Other Health Conditions: Studies have linked PLMS to an increased risk of developing or worsening existing conditions such as cardiovascular disease, hypertension, and mood disorders like depression and anxiety. These associations underscore the importance of managing PLMS to mitigate potential long-term health consequences.
  • Quality of Life: The cumulative effects of poor sleep quality due to PLMS can significantly diminish overall quality of life. Individuals may experience decreased social engagement, mood disturbances, and reduced enjoyment of daily activities.
  • Impact on Relationships: PLMS can also affect interpersonal relationships, particularly if disruptive limb movements disturb a bed partner’s sleep. This can lead to strain in relationships and decreased intimacy.

Recognizing these negative effects underscores the importance of seeking evaluation and appropriate management for PLMS. Addressing underlying causes, such as iron deficiency or co-existing sleep disorders, and implementing effective treatment strategies can help alleviate symptoms, improve sleep quality, and enhance overall well-being.

Ways to Manage Periodic Limb Movement During Sleep

Managing periodic limb movement during sleep (PLMS) involves a combination of lifestyle modifications, medications, and addressing underlying conditions that contribute to the disorder. Here are several evidence-based strategies for managing PLMS:

Improving Sleep Hygiene

  • Regular Sleep Schedule: Maintaining a consistent sleep schedule, including bedtime and wake-up times, helps regulate sleep patterns and may reduce PLMS episodes.
  • Comfortable Sleep Environment: Creating a conducive sleep environment with a comfortable mattress, appropriate room temperature, and minimal noise and light can promote uninterrupted sleep.


  • Dopamine Agonists: Medications that enhance dopamine activity in the brain, such as pramipexole and ropinirole, are commonly used to treat PLMS. These drugs can reduce the frequency and intensity of limb movements during sleep.
  • Benzodiazepines: In some cases, benzodiazepines like clonazepam may be prescribed to help suppress muscle activity and improve sleep quality.

Iron and Mineral Supplementation

  • Iron: Addressing iron deficiency, which is often associated with restless legs syndrome (RLS) and can exacerbate PLMS, may alleviate symptoms. Healthcare providers may recommend iron supplements or dietary adjustments to increase iron intake.
  • Magnesium and Calcium: Ensuring adequate levels of magnesium and calcium through diet or supplements may also help manage symptoms, as deficiencies in these minerals have been linked to RLS and related conditions.

Exercise and Physical Activity

Regular Exercise: Engaging in moderate aerobic exercise, such as walking or swimming, regularly can improve sleep quality and potentially reduce PLMS severity. However, vigorous exercise close to bedtime should be avoided, as it may temporarily increase arousal levels.

Avoidance of Triggers

  • Stimulants: Limiting or avoiding stimulants such as caffeine and nicotine, especially in the hours leading up to bedtime, can help prevent exacerbation of PLMS symptoms.
  • Alcohol: Although alcohol may initially induce sleepiness, it can disrupt sleep patterns and worsen PLMS. Moderation or avoidance of alcohol consumption before bed is recommended.

Treatment of Underlying Conditions

  • Sleep Apnea: Treating co-existing sleep disorders like obstructive sleep apnea can improve overall sleep quality and reduce PLMS episodes.
  • Restless Legs Syndrome (RLS): Managing RLS symptoms effectively through medications and lifestyle modifications may indirectly alleviate PLMS, as the conditions often overlap.

Relaxation Techniques

  • Stress Management: Practicing relaxation techniques such as deep breathing, progressive muscle relaxation, or mindfulness meditation can help reduce stress levels and improve sleep quality, potentially reducing PLMS episodes.

Medical Consultation and Monitoring

  • Sleep Specialist: Consulting with a healthcare provider, particularly a sleep specialist, is essential for accurate diagnosis and personalized treatment planning. Regular monitoring of PLMS symptoms and treatment efficacy allows for adjustments to optimize management outcomes.

By adopting a comprehensive approach that addresses both lifestyle factors and medical treatments, individuals can effectively manage periodic limb movement during sleep and improve their overall sleep quality and well-being.

LifeDNA’s Periodic Limb Movement During Sleep Trait Report

Unlock the secrets of your sleep with LifeDNA’s Periodic Limb Movement During Sleep Trait Report. Our scientifically backed Sleep Report delves into your genetic profile to uncover personalized insights into PLMS and its potential impact on your sleep quality. By understanding your genetic predispositions, you can take proactive steps to optimize your sleep environment, choose appropriate supplements, and tailor lifestyle adjustments to support restorative sleep.

LifeDNA offers a comprehensive suite of genetic reports across seven main categories, including Wellness, Nutrition, Fitness, Skincare, and Personality and Cognition Reports. With nearly 200 trait reports available, each report provides detailed information based on your unique genetic blueprint. Whether you’re interested in enhancing your sleep quality, improving your nutritional choices, or optimizing your fitness regimen, LifeDNA empowers you to make informed decisions that align with your genetic needs.

Embark on your wellness journey today with LifeDNA’s insightful reports. Discover how your genetics influence your daily habits and lifestyle choices, paving the way for a healthier, more balanced life. Take control of your health and well-being by leveraging the power of genetic insights. Visit LifeDNA now to start exploring your genetic reports and unlock a deeper understanding of yourself.


  • Humans vary in their ability to smell odors, with genetic variations near olfactory receptor (OR) genes contributing to these differences.
  • Genetic variation in OR genes affects odor perception and food selection, similar to how genetic differences influence taste.
  • Beta-ionone, a key aroma in foods and beverages, shows extreme sensitivity differences among individuals due to genetics.
  • The genetic variant rs6591536, causing an N183D substitution in OR5A1, is responsible for β-ionone odor sensitivity differences.
  • This variant explains over 96% of observed phenotypic variation, making it similar to a monogenic Mendelian trait.
  • People with the sensitive genotype for β-ionone describe it as “fragrant” and “floral,” while less-sensitive individuals perceive it differently.
  • Sensitivity to β-ionone also influences emotional associations and food/product choices.
  • Understanding genetic variations in OR genes highlights the significant impact of genetics on sensory experiences.
  • Air quality, diet and nutrition, exposure to chemicals, age, health conditions, medications, smoking, hormonal changes, stress, and environmental enrichment can affect sensitivity to beta-ionone.
  • Maintaining good health, avoiding pollutants, regular olfactory training, minimizing stress, staying hydrated, limiting strong chemicals, quitting smoking, engaging in scent enrichment activities, managing health conditions, and consulting healthcare professionals can improve sensitivity to beta-ionone.
  • Alpha-ionone has a woody, floral aroma, while beta-ionone has a sweet, floral fragrance, both are used in perfumes and flavors.
  • Beta-ionone enhances fragrances and flavors, offers aromatherapy benefits, has antioxidant properties, and has potential anti-inflammatory effects.
  • Sensitivity to beta-ionone is influenced by genetics, with specific OR gene variants significantly impacting odor detection and sensory experiences.


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  8. https://pubmed.ncbi.nlm.nih.gov/31678660/
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  10. https://www.webmd.com/sleep-disorders/periodic-limb-movement-disorder
  11. https://www.ninds.nih.gov/health-information/disorders/restless-legs-syndrome
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277795/
  13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639136/
  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717612/
  15. https://myhealth.alberta.ca/Health/Pages/conditions.aspx?hwid=ue5312spec
  16. https://pubmed.ncbi.nlm.nih.gov/38708125/#:~:text=Highlights%3A%20Benzodiazepines%20are%20frequently%20used,day%20are%20most%20frequently%20employed.

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*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

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