jwilzewske: Musicians’ Focal Dystonia Update 2011

L osses incurred in the wounding and in the healing both serve as ‘seeds’ for growth. We cannot wish away the loss, so it is well if we accept the seeds and nurture them, and see what fruit they bear.”

T here have been several dozen readers (TCP/IP addresses in U.S., Canada, U.K., Greece, Italy, Germany) who have landed on this blog in the past 2 weeks by searching Google with “focal dystonia” and related phrases. Some of them used the phrase ‘personalized medicine’ or ‘genomics testing’ as part of their Google search. In response, I want to provide some new resources, beyond ones in my previous focal dystonia-related posts in past years (links below). It is not my intent that all of the resources will be relevant to everybody who reads this post, only that some of the materials will be useful to some of the readers.

W hile I do not have dystonia myself, I know a couple of musicians who do have it. They developed it after years of intensive performance and work at leading conservatories, after achieving mastery of their respective instruments and after having embarked on promising concert careers. For each of these friends, the condition was career-changing. Both are now teaching, primarily; the shift in their attention is source of much joy and satisfaction, surely, and a fantastic treasure in terms of effective, practical pedagogy imparted to the next generation. But it comes at tremendous cost, in terms of foregone income and beauty—performances and recordings prevented, in careers hobbled by focal dystonia.

M y interest in keeping track of current state-of-the-art with regard to diagnosing and treating focal dystonia is in direct proportion to the distress and disappointment I have witnessed in these friends. Besides the recent spate of anonymous searches and CMT page-views, the emails I receive from CMT readers confirm that this condition frequently goes unrecognized or un-diagnosed for years, depending on whether there are dystonia-experienced clinicians accessible to you, ones who specialize in caring for musicians or other performing artists. In other words, if a doctor has never ever seen a case of dystonia before, the probability that he/she will diagnose one now is disproportionately low. This problem is compounded by the fact that focal dystonia does not have obvious signs and symptoms when seen in the clinic.

W ith the intensifying interest in relatively inexpensive direct-to-consumer (DTC) genomic testing from deCODE and 23andme and other companies and with recent years’ trend toward consumers’ taking progressively greater responsibility for diagnosing and managing their own health conditions, I gather together links below, links to the most recent research literature that bears on genetics and genomic polymorphisms that might enable musicians to look at their DTC genomics tests’ raw file download results and bring that evidence with them when they meet with their physicians. Given that the spectrum of focal dystonia is quite broad and pleomorphic, maybe this will help musicians to take charge of the situation, especially if the doctors seem too inclined to ‘wait and see’ or discount the severity of what the patient in front of them is complaining of. Even if the physician has no prior experience with genomics tests per se, it is hard for the physician to be dismissive when the patient in front of him/her is knowledgeable and comes bearing specific evidence with the expectation the evidence will be discussed.

I n this regard, if one of my friends who has focal dystonia discovered that he does have one of the dystonia-associated genomic polymorphisms, then that discovery might be helpful to him and his wife with regard to preventing dystonia in their kids, insofar as the intensity and duration of musical-instrument practice are strongly correlated with triggering the onset of dystonia. One can be a genetic carrier of the genetic variation but remain asymptomatic so long as one doesn’t hit the trigger-point in terms of over-use or over-training. If you are a parent, such information would surely modulate how you approach the musical education of your children...

A t present, researchers have recognized multiple forms of dystonia that have strong association with genetic variations. They have so far identified multiple genes and chromosomal locations responsible for various forms of dystonia. Most of these are rarer and more severe forms than the focal variety that is seen in musicians. But the same genes—and some of the same variations/mutations—have been found to be involved in cases of musicians’ dystonia.

DYT1 (TOR1A) – Early onset-primary dystonia
DYT2 () – Autosomal recessive primary dystonia
DYT3 (TAF1) – X-linked dystonia
DYT4 () – Non-DYT1 spasmodic ‘whispering dysphonia’ [singing]
DYT5 (GCH1) – Dopa-responsive dystonia
DYT6 (THAP1) – Adolescent-onset mixed-type dystonia
DYT7 () – Adult-onset primary dystonia
DYT8 (MR1) – Paroxysmal non-kinesigenic dyskinesia
DYT9 () – Paroxysmal choreoathetosis with dystonic spasticity
DYT10 () – Paroxysmal kinesigenic dyskinesia
DYT11 (SGCE) – Myoclonus dystonia
DYT12 (ATP1A3) – Rapid-onset dystonia-Parkinsonism (RDP)
DYT13 () – Early- and late-onset focal dystonia
DYT15 () - Alcohol-responsive myoclonic dystonia
DYT16 (PRKRA) - Dystonia-Parkinsonism
DYT17 () - Segmental or generalized dystonia with dysphonia [singing]
DYT18 (SLC2A1)
DYT19 () - Episodic kinesigenic dyskinesia 2
DYT20 () - Paroxysmal non-kinesigenic dyskinesia 2

T o the reader who recently emailed me, the Phe205Ile (613T>A; see Calakos 2010, link below) polymorphism in the TOR1A gene on Chr. 9 is associated with jaw/embouchure dystonia in the cases that have been studied to-date, although there may be other genes and polymorphisms associated with that condition/phenotype, too. Unfortunately, this particular SNP polymorphism is not included at this time in the microarray chips that 23andme and deCODEme use for their DTC genomics testing, and it is not available in other presently-available tests either so far as I can tell. There are, however, 7 TOR1A SNPs and 4 TOR1B SNPs that are tested, 16 SNPs in the GCH1 gene, 9 SNPs in SGCE, 2 SNPs in ATP1A3, 6 in MR1, 2 in PRKRA, 2 in TAF1, and so on. These are there in your 23andme raw file download results, ready for you to look at and see whether you do or don’t have a variant polymorphism at one or more of these SNP locations.

A t any rate, there seems to be a pent-up demand for resources, links, referrals, anything at all—an unmet need for new information or updates, year-to-year—plus a considerable amount of new information that has accumulated since I last put up a blog post on this topic. Which is why I gather these things and put them up online right now.

M usicians’ dystonia is a task-specific movement disorder that produces cramping and loss of voluntary motor control of muscles that are involved in highly-trained movements associated with performing music. About 1% of all professional musicians develop musicians’ dystonia, although the percentage may be considerably higher since there are many whose condition is never definitively diagnosed and many whose change of career never comes to the attention of researchers who write the journal articles reporting the nominal 1% prevalence figure.

T he pathophysiology of the disorder is not completely clarified. Findings in neurophysiology testing include reduced inhibitory signals at different levels in the brain, abnormal neuroplasticity, and altered sensory perception. Epidemiologically, there is higher risk for those musicians who play instruments requiring maximal fine-motor skills, such as piano, but the condition also occurs in brass players, double-reed players, and singers. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely-used hand—the right hand in guitarists and lutenists. Preliminary findings also suggest a genetic contribution to focal task-specific dystonia with phenotypic variations including musicians’ dystonia. Treatment options include pharmacological interventions, such as trihexyphenidyl or botulinum toxin-A, as well as retraining programs and ergonomic changes in the instrument. Only a minority of musicians, however, return to fully-normal motor control using the currently available therapies. The non-optimality of current therapies—combined with the expectation that identifying the genes, genetic variations, and receptors that are involved in the condition may lead to new, more-effective therapies targeting those receptors in the nervous system—are what drives the recent genomics-based research in this area.

A t the Glasgow Royal Infirmary’s Department of Physiotherapy, eight musicians recently volunteered to take part in a retraining protocol and were studied by Patrice Berque and collaborators. Intensive ‘constraint-induced therapy’ and motor control retraining at slow speed were the interventions Berque examined. They made video recordings of the subjects playing. They measured ‘Frequency of Abnormal Movements’ scale (FAM), the change in metronome speed achieved during motor control retraining, plus two other dystonia evaluation scales. Over a 12-month period, the FAM scale scores showed statistically and clinically significant decrease in the number of abnormal movements per second of instrumental playing. Statistically, significant changes did not appear until about 8 months of therapy. Berque’s results suggest that a combination of constraint-induced therapy and specific motor control retraining may be a successful strategy for the treatment of musicians’ focal dystonia, and suggest that many months may elapse before significant progress occurs.

I n Cheng’s series, three people were found to have the delGAG deletion in the TOR1A (DYT1) gene, and two patients were found to have polymorphisms in the THAP1 gene (224A>T, 449A>C). The overall mutation frequency was 4.5% in Cheng’s patients, with TOR1A mutations found in 2.7% and THAP1 mutations found in 1.8%. No mutations were detected in the control population of normal Chinese. The significance with respect to musicians’ dystonia is not addressed by Cheng, but, by implication, we may anticipate that the genomic epidemiology of musicians’ dystonia may be subject to racial/ethnic variations in much the same manner as the genomic epidemiology of other forms of dystonia varies by race and ethnic ancestry.

1 comment:

JESSICAFebruary 22, 2019 at 7:39 PM
ALL THANKS TO DR WILLIAMS FOR THE GREAT DEED HE HAVE DONE FOR MY DAUGHTER?
My daughter suffered from dystonia for more than 7 years which we started experiencing in her when she turned 4 year and 5 months we all thought it will end but got even worse as days went by. We tried all several treatments and therapy prescribed by various doctors we met but to no avail, she lost total concentration and always complain of neck discomfort . She usually tells me she haves jerky head movements . This were steady disorder that disrupted her entire life, even at night she slept less because of this.It was during a casual conversation with a friend that i learned about Dr Williams herbal medicine I was able to contact him on his email address. and give him all the necessary information that he needed,few day later he sent me the herbal portion and his medicine was able to restore her back to normal and she is very okay now without any side effects whatsoever. If you have dystonia , do not hesitate to contact him on drwilliams098675@gmail.com for advice and for his product. I hope this also helps someone out there.

Tuesday, February 1, 2011

Musicians’ Focal Dystonia Update 2011

1 comment: