MIRROR movements are involuntary movements that mimic, and occur simultaneously with, voluntary movements on the opposite side of the body. The movements are known to occur because of a failure in communication between the two sides of the nervous system. They are thought to be normal during infancy and early childhood, but usually diminish with age and disappear altogether by the age of 10, following maturation of the corpus callosum, the massive bundle of nerve fibres connecting the left and right hemispheres of the brain.
A large genetic study published online in the journal Science now shows that mirror movements are caused by a single genetic mutation. The mutation is located within a gene that encodes a well-known protein involved in guiding growing nerve fibres to their proper destination during development, and gives rise to mirror movements because the connections between the two brain hemispheres fail to form properly.
Mirror movements are uncommon in adults, but they are known to be heritable, and can occur sporadically for a wide variety of reasons. They are a symptom of Parkinson’s Disease, cerebral palsy, schizophrenia and obsessive compulsive disorder; they can occur during epileptic seizures, or following a stroke or some other insult to the brain; they are also associated with alien hand syndrome, and can even occur in otherwise healthy people during prolonged physical exertion or in severe fatigue.
The movements almost always affect the arms and hands, but legs can also be affected. They are usually relatively subtle, so that individuals can find them to be inconvenient and embarrassing but not disabling. Their subtlety can be seen in this film clip of a 21-year-old soldier, who was banned from using ammunition by his senior officers, because of fears that he might cause a firearm-related accident. When he flexes the fingers of his right hand, as if to pull a trigger, the fingers on his left hand perform similar but more subtle movements:
Myriam Srour of the University of Montreal and her colleagues previously described two large families – one French-Canadian, the other Iranian – that contain members affected by mirror movements. The researchers discovered the mutation by performing a genome-wide association study, which is designed to identify genetic variants associated with a particular condition, and is performed by comparing the genomes of affected individuals with those of large numbers of healthy controls.
All of the affected family members were found to harbor the same point mutation in the Deleted in Colorectal Cancer (DCC) gene, which encodes a receptor for a classical axon guidance molecule called Netrin-1. The mutation was not found in unaffected family members, or in some 1,300 unrelated controls. The researchers then isolated the gene from from the affected individuals, and found that the mutation produces a shortened form of the DCC protein which is missing the Netrin-1-binding region.
First identified almost 20 years ago, DCC and Netrin-1 are highly conserved in evolution, and their functions are very well characterized. Versions of both genes are found in fruit flies, nematode worms and vertebrates, and the proteins they encode serves the same function in all of these organisms. One important function of the interaction between DCC and Netrin-1 is to guide growing nerve fibres towards the midline of the nervous system during embryonic development, and to help them make steering decisions once they reach it.
DCC is found in the extending tips of the fibres, while Netrin-1 is synthesized and secreted by midline cells. The tips of the fibres are attracted to the Netrin signal, growing towards the areas where it is most highly concentrated, so that the nerve fibres cross from one side of the nervous system to the other. The interaction between DCC and Netrin-1 is therefore important for the proper formation of the commissures, the fibre tracts that connect the left and right sides of the nervous system. In mammals, the largest of these is the corpus callosum, but there are several smaller ones on the brain, and even smaller ones at regular intervals along the length of the spinal cord. Given its well established role in commissure formation, the finding that DCC mutations result in mirror movements are not particularly surprising, but the results do confirm that the protein plays the same role in the human nervous system as it does in other organisms.
Srour, M., et al. (2010). Mutations in DCC Cause Congenital Mirror Movements. Science 328: 592-592. DOI: 10.1126/science.1186463.