Sleep Movement

Have you noticed your partner twitching in their sleep? Or perhaps you wake yourself up because your arms and legs twitch repeatedly in the night? You’re not alone! Everyone twitches in their sleep to some extent. Did you know the average person moves 13 times an hour while sleeping?

Some people, however, tend to twitch more than the average, which may seem like a bit of a nuisance if you wake up sleep-deprived more often than not. This additional twitching may be a result of a condition called Periodic Limb Movements in Sleep (PLMS), which is estimated to affect 4-11% of adults [1]. Jump to reference section: [1].

PLMS involves repetitive involuntary movements or twitches in the arms, legs or feet of a person. These movements generally last from five to 90 seconds. To diagnose PLMS, electrodes are placed on the arms and legs of a sleeping person. These electrodes help researchers measure and monitor the total number of periodic limb movements in the person. Don’t worry, this is not something you need to do if you’re only here to learn more about your genetics! 

What causes sleep movements?

Many conditions, such as PLMS, can lead to movement during sleep. This includes disorders such as restless leg syndrome, sleep-related leg cramps, and sleep-related teeth grinding. Currently, the exact cause of PLMS is largely unknown. There are, however, a number of genetic and non-genetic factors that have been associated with the condition. 

In some people, there may also be one or more genetic variants that explain the twitching at night. A combination of variants on a number of genes, such as the BTBD9 gene, the TOX3 gene, and the MEIS1 gene, significantly increases your risk of PLMS. The more risk-increasing variants you have, the more likely that you will have PLMS. 

Below, we provide you with an overview of some of the most significant genetic variants that increase your risk of PLMS. Please note, although we discuss three variants, there are many more genes that have been linked to the condition.

The genetics of sleep movement 

Research has suggested that there may be a link between some genetic variations in the BTBD9 gene and sleep movement conditions such as PLMS and restless leg syndrome. The BTBD9 gene contains the instructions for your body to produce a protein called “BTB domain-containing 9”. 

But why is this gene important? At the moment, little is known about the function of BTBD9, although studies on flies and mice suggest it may play a vital role during sleep [2] Jump to reference section: [2] and movement [3] Jump to reference section: [3] . In humans, studies suggest that variations of the BTBD9 gene, and more specifically the A variant,  is associated with PLMS and restless leg syndrome. 

Individuals inherit two copies of every gene from their parents; one inherited from each parent. If an individual inherits two copies of the A variant of BTBD9 gene, called rs3923809 [4] Jump to reference section: [4] , the individual has two [5] Jump to reference section: [5] to three times [6] Jump to reference section: [6] as many PLMS movements per hour compared to an individual with two versions of the G variant. In more scientific terms, the A variant is the “risk allele”, i.e. it increases the risk of a person having PLMS [7] Jump to reference section: [7] . To put this into perspective, the average person has 13 sleep movements per hour. An individual with two A variants is likely to have as many as 26 to 39 sleep movements per hour. 

Similar to the BTBD9 gene, variants of various other genes have also been implicated in PLMS. For example, the T variant (rs3104788) of the TOX3 gene -- a gene that plays a role in regulating protein formation (the building blocks of our cells) - is significantly associated with PLMS. Although the T variant significantly increases an individual’s risk of PLMS, there is no exact statistical impact for the variant. This is because various other factors, such as iron levels, blood sugar levels and other health conditions, are associated with PLMS. Some researchers estimate that individuals with two T variants are 1.35 times more likely to experience PLMS [8] Jump to reference section: [8] , but research to quantify the effect of the variant is still ongoing.

Another gene that has implications in PLMS is the MEIS1 gene, which plays an important role in the regulation of protein synthesis - an important process in the body that focuses on repairing wear and tear. This gene is thought to play a role,  not only in PLMS, but also in restless leg syndrome, which is often associated with an increased risk of PLMS [9] Jump to reference section: [9] . To make matters slightly confusing, the MEIS1 also has a G variant (rs12469063), which similar to the T variant in TOX3, increases the odds of a person to have PLMS movements by 1.35 times [10] Jump to reference section: [10] . 

Non-Genetic factors associated with PLMS

PLMS is not only associated with genetic factors. Non-genetic factors, such as iron deficiencies [11] Jump to reference section: [11] , can increase a person's risk for PLMS [12] Jump to reference section: [12] . Similarly, some medications, such as dopamine blockers, may also increase a person’s risk for PLMS. The condition may also be attributed to uncontrolled blood sugar (such as in diabetics [13] Jump to reference section: [13] ), restless leg syndrome, a spinal cord tumor, and ADHD [14] Jump to reference section: [14] . 

Managing PLMS

While twitching at night can be harmless for the most part, it may lead to poor sleep in the person or their partner. In these cases, people may seek ways to manage their symptoms. To correctly manage symptoms, doctors may need to identify the mechanism behind their symptoms; is it genetic or non-genetic? If the condition is caused as a side effect of medications, doctors may prescribe medications to counteract these side effects [15] Jump to reference section: [15] , or change prescriptions to ensure PLMS symptoms are avoided. Alternatively, if the condition is caused due to an iron deficiency or unmanaged blood sugars, the fix may be as simple as taking iron tablets or managing blood sugar.