SNP Shot: Genomic Insights

Restless legs syndrome (RLS) is a neurological disorder characterized by an overwhelming need to move the legs. This urge is prompted by unusual or unpleasant sensations, often described as crawling, pulling, or itching, located deep inside the legs. These sensations typically arise when sitting or lying down and are most intense at night. Moving the legs, through activities like kicking, stretching, rubbing, or pacing, offers temporary relief from the discomfort. The unpleasant sensations and the consequent need to move often disrupt sleep, making it hard to fall or stay asleep.

The severity of RLS symptoms varies greatly. Some individuals experience mild symptoms only a few times per month, while others with more severe cases have symptoms every night. In extreme cases, the uncomfortable sensations may extend beyond the legs, affecting the arms or other body parts.

Many individuals with RLS also experience involuntary, repetitive leg movements, particularly during sleep or while relaxed or drowsy. These movements are termed periodic limb movements of sleep (PLMS) when they occur during sleep and periodic limb movements of wakefulness (PLMW) when they occur while awake. It remains unclear whether PLMS and PLMW are intrinsic features of RLS or separate but related conditions.

Both RLS and PLMS can negatively impact sleep quality and duration. As a consequence, individuals with these conditions may struggle with daytime concentration and may develop mood changes, depression, or other health issues.

Researchers have identified two main types of RLS: early-onset and late-onset. Early-onset RLS begins before the age of 45, sometimes even in childhood, and its symptoms typically worsen gradually over time. Late-onset RLS, on the other hand, begins after age 45, and its symptoms tend to progress more rapidly.

Inheritance:

The inheritance of RLS is complex, influenced by a combination of genetic and environmental factors. The disorder often clusters in families, with 40% to 90% of affected individuals reporting at least one affected first-degree relative (parent or sibling). Many families have multiple affected members. Studies suggest that early-onset RLS has a stronger familial tendency than late-onset RLS. In some families, RLS appears to follow an autosomal dominant inheritance pattern, meaning that only one copy of a mutated gene in each cell is needed to cause the disorder. However, the specific genetic changes responsible for RLS in these families have not yet been identified.