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Restless legs syndrome, most common in old age, appears to be programmed in the womb

Restless legs syndrome, most common in old age, appears to be programmed in the womb

Restless legsWhile the sleep disorder called “restless legs syndrome” is more typical of older than younger people, it looks as though it’s programmed in the womb. And a group led by Stanford neurologist Juliane Winkelmann, MD, has pinpointed for the first time the anatomical region in the brain where the programming takes place.

Restless legs syndrome, or RLS, is just what it sounds like: a pattern of unpleasant sensations in the legs and the urge to move them. It has been described as a feeling similar to the urge to yawn, except that it’s situated in the legs or arms instead of the upper torso and head.

Estimates vary, but something on the order of one in ten Americans has RLS. Women are twice as likely as men, and older people more likely than young people, to have it. This urge to move around comes in the evening or nighttime, and can be relieved only by – wait for it – moving around. Needless to say, that can cause sleep disturbances. In addition, RLS can lead to depression, anxiety and increased cardiovascular risk.

Very little is known about what actually causes RLS, although it’s known to be highly heritable. Although a number of gene variants (tiny glitches in a person’s DNA sequence) associated with the condition have been discovered, each by itself appears to contribute only a smidgeon of the overall effect, and nobody knows how.

Winkelmann has been exploring the genetic underpinnings of RLS at length and in depth. In a just-published paper in Genome Research, she and her colleagues have shown that one gene variant in particular depresses the expression of a protein involved in organ development and maintenance. The DNA abnormality Winkelmann’s team zeroed in on occurs not on the gene’s coding sequence – the part of the gene that contains the recipe for the protein for which the gene is a blueprint – but rather on a regulatory sequence: a part of the gene that regulates how much of that protein (in this case, the one involved in organ development and maintenance) gets made, and when.

The kicker (pardon my pun) is that the regulatory sequence in question seems to be active only during early brain development and only in a portion of brain that is destined to become the basal ganglia, a brain region well known to be involved in movement.

“Minor alterations in the developing forebrain during early embryonic development are probably leading to a predisposition in the [basal ganglion],” Winkelmann says. “Later in life, during aging, and together with environmental factors, these may lead to the manifestation of the disease.”

(Wondering if you’ve got RLS? Check this out.)

Previously: National poll reveals sleep disorders, use of sleeping aids among ethnic groups, Caucasian women most likely to have restless leg syndrome
Photo by Maxwell Hamilton

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