The genetic basis of dystonia

Published on August 5, 2014   32 min

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My name is Professor Tom Warner. I am a professor of clinical neurology at the Institute of Neurology at UCL, and this talk is concerning the genetic basis of the dystonias.
The dystonias are an unusual group of hyperkinetic movement disorders which are diagnosed clinically, usually by the presence of involuntary sustained muscle spasms, easily recognizable twisting and repetitive movements, and posturing, quite often of the limbs. At a very simplistic level they're caused by abnormal processing of motor commands within the central nervous system. They are often action-induced, so they're brought on by movements. And like many involuntary movement disorders, they abate during sleep. Dystonia itself can affect almost any part of the body, including the neck, the eyes, limbs, larynx, mouth, and tongue, and so can be very clinically heterogeneous.
There's a long history of description of dystonia in neurological literature. Originally, it was termed athetosis, which is effectively synonymous with the term dystonia, and it goes back to Spanish descriptions in 1897. And the gentleman described has marked posturing of the limbs, the feet. There is torticollis and the head is pulled back, which is what we refer to as retrocollis, and there's also clearly an extended lumbar lordosis. Over the years, familial forms have been described, and in 1908, the first autosomal dominant family was described. And then the term dystonia actually arose from Oppenheim in 1911. In the 20th century the literature extended and, particularly, it was highlighted by David Marsden from the Institute of Neurology, where he realized there was a link between these severe, generalized, often familial forms, and the much more common sporadic focal forms affecting one part of the body, such as torticollis and writer's cramp. He realized that these were actually passed off a pathogenic spectrum in terms of the underlying processes in the central nervous system and that they were linked together. Stanley Fahn, the other doyen of dystonia, in New York went on to study these phenotypes more. And this forms the basis of what we really understand clinically about dystonia.