ATHLETE PRIMARY AND SECONDARY DYSTONIA

“Dystonia is a neurological movement disorder that causes the muscles to contract or spasm involuntarily. This disorder is caused by a defect in the mechanisms that allow muscles to relax when they are not in use. The muscle spasms distort the body into awkward, irregular and uncomfortable positions. There are different forms of dystonia, some that affect a single area of the body and others are considered to be generalized and spread throughout large muscle groups. The condition affects about 300,000 people in North America with varying degrees of disability and pain. [Surgeons Trying Pacemaker Procedure For The Brain, Doctors Find Deep Brain Stimulation Can Help Patients Deal With Neurological Disorder, ABC 7 News, Denver, Apr 14, 2010]

Coaches, Parents and the entire Athletic Community should be cognizant of the sudden failure of an Athlete to execute otherwise easy athletic motor actions because of the unknown sudden onset of Dystonia. In some cases, it has been described as the YIPS in Sports, when Athletes suddenly cannot execute a previously simple athletic action i.e. throwing a baseball, shooting a basketball, swimming strokes, kicking a football to name a few.

Coaching punishment of an Athlete for failure to execute. because of the onset of the neurological disorder, like Dystonia, would be horrible, adding shame and inhumane treatment to an already disabling progressive disease.

“Billy Barnhard’s father taught him how to hit at 3 by pitching plastic baseballs to him in the basement. Barnhard played baseball until he was 7. That’s when he started having trouble speaking, and moving his limbs properly. Doctors eventually diagnosed him with a disorder called generalized dystonia. Barnhard, now 18, can no longer speak and is forced to use technology, specifically his iPad, to communicate.” Dysphnonia is both a focal and generalized dystonia.

“The disease is caused by a genetic disorder which results in a defect in a protein called Torsin A.[1] A mutation in the DYT1 gene causes the loss of an amino acid, glutamic acid, in the Torsin A protein. The defective protein creates a disruption in communication in neurons that control muscle movement and muscle control. This mutation is most usually inherited from a parent, but can occur sporadically.[2] The disease is caused by a dominant allele, meaning that the person affected needs only one copy of the mutated DYT1 gene to have symptoms.[3] However, only 30 to 40% of those that do have the gene actually have symptoms, leading researchers to believe that there are other factors involved.[4]

Dystonia is prevalent among the Jewish population and populations of immigrants to America, who were sequestred and waiting for years in Europe and who were thought to have intermingled with the Jews prior to immigration. “The disease is more commonly found among Polish Ashkenazi Jews. The occurrence of torsion dystonia in the Ashkenazi Jewish population as stated by the Department of Epidemiology and Public Health of Yale University School of Medicine in New Haven, CT; “Reports dating to the beginning of this century describe Ashkenazi Jewish (AJ) families with multiple cases of ITD (Inherited Torsional Dystonia) either in siblings (Schwalbe 1908; Bernstein 1912; Abrahamson 1920) or in parents and offspring (Wechsler and Brock 1922; Mankowsky and Czerny 1929; Regensberg 1930).

The first comprehensive evaluation of the mode of inheritance of ITD in Jewish and non-Jewish families was described by Zeman and Dyken (1967), who concluded that the disorder was inherited as an autosomal dominant with incomplete penetrance in both populations. Although they concluded that the gene frequency was higher in the AJ population than in non-Jews, no difference in mode of inheritance or disease mechanism was construed.”

A 1969 study of torsion dystonia patients found an average IQ 10 points higher than controls matched for age, sex and ethnic background.[7]
References. This ia a movement disorder, not a cognitive disease.
[Ozelius, L. J.; Hewett, J. W.; et al (1997). “The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein”. Nature Genetics. 17 (1): 40–8]
[Hjermind, L. E.; Werdelin, L. M.; Sørensen, S. A. (2002). “Inherited and de novo mutations in sporadic cases of DYT1-dystonia”.European J of Human Genetics. 10 (3): 213–6]
[Risch, N. J.; Bressman, S. B.; et al (1990). “Segregation analysis of idiopathic torsion dystonia in Ashkenazi Jews suggests autosomal dominant inheritance”. Am J Human Genetics. 46 (3): 533–8]
[Cloud, L. J.; Jinnah, H. A. (2010). “Treatment strategies for dystonia”. Expert Opinion on Pharmacotherapy. 11 (1): 5–15]
[Delnooz, C. C.; Van De Warrenburg, B. P. (2012). “Current and future medical treatment in primary dystonia”. Therapeutic Advances in Neurological Disorders. 5 (4): 221–40]
[Eldridge, R.; Harlan, A.; Cooper, I.; Riklan, M. (1970). “Superior Intelligence in Recessively Inherited Torsion Dystonia”. The Lancet. 295 (7637): 65–67]

THAP1 gene in three Amish-Mennonite families with mixed-onset primary torsion dystonia (also known as DYT6 dystonia). Another mutation in a German family with primary torsion dystonia suggests that THAP1 mutations also cause dystonia in other ancestry groups. We demonstrate that the missense mutation impairs DNA binding, suggesting that transcriptional dysregulation may contribute to the phenotype of DYT6 dystonia. [Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia, Tania Fuchs et al, Nature Genetics 41, 286 – 288 (2009) 1 February 2009]

“Dystonia is a neurological disorder, much like ALS, that causes abnormal posturing and twisting of particular body parts. Unlike ALS, dystonia is not fatal and the disease stops spreading through the body in most cases. There is no cure. [Maryland law provides athletic opportunities for disabled By Allen Etzler, February 16, 2013, Capital News Service, Fox News http://www.foxnews.com]

“Several data indicate the role of tau protein in axonal growth and in the establishment of neuronal polarity. In mature neurons, the protein is specifically located in the axon whereas it is absent in dendritic arbor (14,15) and inhibition of tau expression by means of an antisense technique revealed that this protein is essential for axon growth (18).

Tau function is regulated by phosphorylation and this phosphorylation seems to be strongly associated with cell polarity. In fact, during the period of axonogenesis in the nascent neuron, the protein is more highly phosphorylated in the soma than in the axon. This proximo-distal gradient is dynamic and potentially regulated by upstream signals (19). Indeed, during the development of the rat brain there is a temporally defined switch in the expression of tau isoforms, followed by a reduction in tau phosphorylation, suggesting a progressive reduction in neuronal plasticity and a reinforcement of mature neuronal cytoarchitecture (20,21).

“Furthermore, although no neuropathological changes were found in the brains of patients with generalized DYT1 dystonia, some cases of primary focal disease display neuronal loss and the presence of neurofibrillary tangles in the locus coeruleus and in the substantia nigra pars compacta (22). In dystonia muscolorum (dt), a hereditary sensory neuropathy of the mouse characterized by progressive loss of limb coordination, Dolpe et al. (23) observed a marked reduction of microtubule associated proteins with accumulation of neurofilaments in axonal swelling.

Dystonia is also a common manifestation of at least two tauopathies (TAU protein pathologies), in which tau positive neurofibrillary pathology is the most predominant neuropathological feature (24): progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD). In fact, unilateral limb dystonia and arm levitation have been reported in some cases of PSP (25), while dystonia, often accompanied by painful rigidity and fixed contractures, is a common symptom in the initial phase of CBD (26).

An intriguing possibility is that in neurons TorsinA, similarly to OOC-5 in nematodes, directs and/or stabilizes the subcellular localization of MARKs/PAR1 kinases, which may in turn phosphorylate microtubule associated proteins, such as tau. In this way, TorsinA may contribute to maintaining the appropriate site-directed polarization and control neurite outgrowth.

In conclusion, TorsinA appears to be involved in a cellular mechanism responsible for the management of proper addressing and folding of specific proteins and disappearance and/or alteration of these mechanisms may result in protein aggregation and cell dysfunction. Thus, functional TorsinA seems to have a protective capacity within cells. Solving the mystery of TorsinA’s cellular function may have important implications in dystonia as well as Parkinson’s disease and other neurological disorders. [TorsinA, microtubules and cell polarity by Giulia Ferrari Toninelli, PierFranco Spano, Maurizio Memo, Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Brescia, Italy, Dept of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Via Europa 11, 25123 Brescia, Italy]

TAU Protein Pathology occurs in fooyball athletes’ TBI and Concussion, in addition to Dystonia. “Traumatic brain injury (TBI) due to contact sports may involve TAU entanglement of neuron cells and cause chronic behavioral, mood, and cognitive disturbances associated with pathological deposition of tau protein found at brain autopsy,” particularly Pro Football Players. Scientists used positron emission tomography (PET) scans after intravenous injections of FDDNP that revealed deposition of tau in the brain where the brain lit-up. In the past, only autopsy was indicative. This may offer a means for identification prior to death of neurodegeneration in contact-sports athletes. [Gary W. Small, M.D., et al Am J Geriatr Psychiatry 21:2, February 2013]

“Objective: Mild traumatic brain injury due to contact sports may cause chronic behavioral, mood, and cognitive disturbances associated with pathological deposition of tau protein found at brain autopsy. To explore whether brain tau deposits can be detected in living retired players, we used positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]- 2-naphthyl}ethylidene)malononitrile (FDDNP). Conclusions: If future research confirms these initial findings, FDDNP-PET may offer a means for premorbid identification of neurodegeneration in contact-sports athletes. The small sample size and lack of autopsy confirmation warrant larger, more definitive studies. (Am J Geriatr Psychiatry 2013; 21:138e144)

Dystonia, which is sometimes difficult to diagnose and won’t fit into one diagnostic box, because there are no pathognomonic tests for the disease. The following is a classification of the Dystonia Neurological Disorder, but please understand that it is not all inclusive.

Classification of Dystonia. “Dystonia is generally classified in three ways:
• Age of onset
• Bodily distribution of symptoms
• Cause

Age of Onset
“The symptoms of dystonia may begin during childhood (i.e., early onset), adolescence, or adulthood (e.g., 30s to 50s or later, known as late-onset dystonia). For example, the symptoms of generalized dystonia or dopa-responsive dystonia (DRD) may begin during childhood or adolescence. Most cases of early-onset dystonia are thought to occur as the result of an inherited defect in a gene. Other cases may result from a spontaneous change in a gene or head trauma. Certain focal dystonias such as cervical dystonia (spasmodic torticollis), blepharospasm, writer’s cramp, and spasmodic dysphonia are examples of late-onset dystonias. Unlike early-onset dystonia, the causes of late-onset dystonia are variable. The age of onset may be a factor in determining the probability of disease progression. Generally, the earlier the onset of symptoms, the more likely the chance of progression with advancing age.

Bodily Distribution of Symptoms
“Dystonia may also be classified as follows, according to the bodily distribution of symptoms:
• Focal dystonia
• Segmental dystonia
• Multifocal
• Generalized

Focal Dystonia
“Symptoms may be focal or limited to one region of the body, such as the neck or an arm or a leg. There are many different types of focal dystonia.

“Blepharospasm is marked by involuntary contraction of the muscles that control the movement of the eyelids. Symptoms may range from intermittent, painless, increased blinking to constant, painful, eye closure leading to functional blindness. Blepharospasm must be differentiated from different ptosis etiologies.

“In patients with cervical dystonia (CD), also known as spasmodic torticollis, muscle spasms of the head and neck may be painful and cause the neck to twist into unusual positions or postures. Spasms may be intermittent or constant.

“Oromandibular and lingual dystonia are characterized by forceful contractions of the muscles of the lower face causing the mouth to open or close. Chewing and unusual tongue movements may also occur.

“In spasmodic dysphonia (SD), also known as laryngeal dystonia, the muscles in the larynx are affected. SD is marked by difficulties in either opening or closing the vocal cords. This causes the voice to have either a strained, hoarse, strangled, or whispering quality.

“In limb dystonia, there are involuntary contractions of one or more muscles in the arm, hand, leg, or foot. These types of focal dystonias include writer’s cramp, musician’s cramp, and other occupational dystonias.

Segmental
“Symptoms affect two adjacent areas of the body, such as the head and neck or arm and trunk.

Multifocal
“Symptoms affect two areas of the body that are not next to each other, such as the two arms, or an arm and a leg.

Generalized
“Symptoms begin in an arm or a leg and advance, becoming more widespread. Eventually, the trunk and the rest of the body are involved.

Causes of Dystonia
“In primary or idiopathic dystonia, dystonia occurs as a solitary symptom and is not associated with an underlying disorder. Many cases are believed to be hereditary and occur as the result of a faulty gene(s). For example, most cases of early-onset primary dystonia are due to a mutation in the DYT-1 gene. Early-onset dystonia that occurs as a result of this disease gene is the most common and severe type of hereditary dystonia. Other, rarer, genetic causes of primary dystonia are also known.

“In secondary or symptomatic dystonia, dystonia occurs because of another underlying disease process. The list of possible causes is long, and includes:
• Wilson disease
• multiple sclerosis
• stroke
• brain trauma
• medications

“In adults, the most common type of secondary dystonia is tardive dystonia, due to dopamine-blocking drugs. In most patients, symptoms occur some time after ongoing exposure to the drug. Other movement disorders may also be caused by neuroleptics, the most common of these being dyskinesia. [Movement Disorders, WE MOVE 2013 Virtual library, http://www.mdvu.org/library/disease/dystonia/dys_mcla.asp]

TAU protein deposition has been advanced as a cause for the various forms of Dystonia following Traumatic Brain Injury TBI and Concussion. [CONCUSSION TAU AND MOLECULAR PATHOLOGY http://www.cappaa.com/category/tau-protein-concussion , Athlete Safety 1st]

Dystonia from Trauma

Dystonia symptoms may follow trauma to the head, and/or trauma to a specific body area.

Dystonia symptoms following head trauma often affect the side of the body which is opposite to the side of the brain injured by the trauma. Examples of peripheral injury include oromandibular dystonia following dental procedures, blepharospasm following surgery or injury to the eyes, and cervical dystonia following whiplash or other neck injury. Symptoms of trauma-induced dystonia may be paroxysmal (meaning that they occur in episodes or “attacks” of symptoms), not respond to sensory tricks, and persist during sleep.

Brain trauma will often manifest in observable lesions in the brain that can be assessed by neuroimaging techniques. Onset of symptoms may be delayed by several months or years after trauma. Clues to whether dystonia to a specific body part can be attributed peripheral injury to that body area include:

1. The injury is severe enough to cause local symptoms that persist for at least two weeks or require medical evaluation within two weeks;
2. The onset of the movement disorder occurs within a few days or months (up to a year) after the injury;
3. The symptoms relate anatomically to the injured part of the body.

In addition to dystonia, movement disorders that are believed to result from brain and peripheral trauma include parkinsonism, tremors, chorea, myolconus, tics, and hemifacial or hemimasticatory spasm.

Terms used to describe trauma-induced dystonia include: injury-induced, peripherally-induced (when trauma is to affected body area, not brain), post-traumatic dystonia, causalgia-dystonia syndrome, reflex sympathetic dystrophy with dystonia

Diagnosis

Many of the ascribed causes of secondary dystonia are based on historical information or subtle characteristics of the symptoms, and have no diagnostic, radiologic, serologic, or other pathologic trademark.

Treatment

Oral medications are often the mainstay of treatment for secondary dystonia. Although there is no single drug that helps an overwhelming number of individuals, there are several that may be of benefit. These oral medications include levodopa, trihexyphenidyl, clonazepam, and baclofen (oral and intrathecal—especially for dystonia and spasticity). Medications may be taken in combination.

Botulinum toxin injections may be used to treat specific body parts that may be affected, such as the neck, jaw, hands, or feet.

Several surgical techniques may be appropriate for select individuals who do not respond to medications and botulinum toxin injections. These include ablative surgeries such as pallidotomy and thalamotomy, intrathecal baclofen, and deep brain stimulation. [Dystonia Medical Research Foundation Canada, 305-121 Richmond Street West • Toronto, Ontario • M5H 2K1 , Tel: (416) 488-6974 • Fax: (416) 488-5878]

Dystonia: Causes, Types, Symptoms, and Treatments

Dystonia is a movement disorder. With dystonia, a person’s muscles contract uncontrollably. The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures. Dystonia can affect one muscle, a muscle group, or the entire body. Dystonia affects about 1% of the population, and women are more prone to it than men.

What Are the Symptoms of Dystonia?

Symptoms of dystonia can range from very mild to severe. Dystonia can affect different body parts, and often the symptoms of dystonia progress through stages. Some early symptoms include:

• a “dragging leg”
• cramping of the foot
• involuntary pulling of the neck
• uncontrollable blinking
• speech difficulties
• writer’s cramps
• fasiculations

Stress or fatigue may bring on the symptoms or cause them to worsen. People with dystonia often complain of pain and exhaustion because of the constant muscle contractions.

If dystonia symptoms occur in childhood, they generally appear first in the foot or hand. But then they quickly progress to the rest of the body. After adolescence, though, the progression rate tends to slow down.

When dystonia appears in early adulthood, it typically begins in the upper body. Then there is a slow progression of symptoms. Dystonias that start in early adulthood tends to remain focal or segmental. Focal dystonias affect just one part of the body. Segmental dystonias affect two or more adjacent parts of the body.

What Causes Dystonia?

Most cases of dystonia do not have a specific cause. Dystonia seems to be related to a problem in the basal ganglia. That’s the area of the brain that is responsible for initiating muscle contractions. The problem involves the way the nerve cells communicate.

Acquired dystonia is caused by damage to the basal ganglia. The damage could be the result of:
• brain trauma
• stroke
• tumor
• oxygen deprivation
• infection
• drug reactions
• poisoning caused by lead or carbon monoxide

Idiopathic or primary dystonia is often inherited from a parent. Some carriers of the disorder may never develop a dystonia themselves. And the symptoms may vary widely among members of the same family.

Review: Dystonias are classified by the body part they affect:
• Generalized dystonia affects most of or all of the body.
• Focal dystonia affects just a specific body part.
• Multifocal dystonia affects more than one unrelated body part.
• Segmental dystonia involves adjacent body parts.
• Hemidystonia affects the arm and leg on the same side of the body.

Dystonias can also be classified as syndromes based on their patterns:
• Blepharospasm is a type of dystonia that affects the eyes. It usually begins with uncontrollable blinking. At first, typically, it affects just one eye. Eventually, though, both eyes are affected. The spasms cause the eyelids to involuntarily close. Sometimes they even cause them to remain closed. The person may have normal vision. But this permanent closing of the eyelids makes the person functionally blind. Bright lights might precipitate blepharospasms.
• Cervical dystonia, or torticollis, is the most common type. Cervical dystonia typically occurs in middle-aged individuals. It has, though, been reported in people of all ages. Cervical dystonia affects the neck muscles, causing the head to twist and turn or be pulled backward or forward.
• Cranial dystonia affects the head, face, and neck muscles.
• Oromandibular dystonia causes spasms of the jaw, lips, and tongue muscles. This dystonia can cause problems with speech and swallowing.
• Spasmodic dystonia affects the throat muscles that are responsible for speech.
• Tardive dystonia is caused by a reaction to a drug. The symptoms are typically only temporary and treatable with medication.
• Paroxysmal dystonia is episodic. The symptoms occur only during attacks. The rest of the time, the person is normal.
• Torsion dystonia is a very rare disorder. It affects the entire body and seriously disables the person who has it. Symptoms generally appear in childhood and get worse as the person ages. Researchers have found that torsion dystonia is possibly inherited, caused by a mutation in the gene DYT1.
• Writer’s cramp is a type of dystonia that only occurs while writing. It affects the hand and/or forearm muscles.
[Dystonia WebMD Home ,Brain & Nervous System Health Center]

Dystonia after head trauma

Abstract: Dystonia is a rare consequence of head trauma. We describe 10 such cases and review 19 similar patients reported in the literature. Twenty-two of the 29 patients suffered head injury during the first or second decade of life. There was a variable delay between the head trauma and the onset of dystonia. In 18 cases with severe head injury, this interval (median, 18 months; range, 1 month to 9 years) was longer than in 11 cases with mild head injury (median, 14 days; range, 3 days to 5 years). In our series, nine of the 10 cases started as a focal dystonia and one as a hemidystonia. The dystonia progressed and spread over several months or years. Two cases remained as focal dystonias, but the others developed segmental, hemi-, multifocal, or generalized dystonia. On brain imaging studies (CT or MRI), the most frequent lesion site was in the contralateral basal ganglia or thalamus, but two cases had normal brain scans. Dysfunction of the lenticulothalamic neuronal circuit seems to be related to the development of dystonia following head trauma.
[Dystonia after head trauma, M. S. Lee, MD, PhD, J. O. Rinne, MD, PhD, A. Ceballos-Baumann, MD, P. D. Thompson, MD, PhD and C. D. Marsden, FRS, DSc, University Department of Neurology (Drs. Lee, Rinne, Ceballos-Baumann, Thompson, and Marsden), Institute of Neurology, Queen Square, London, UK; the Department of Neurology (Dr. Lee), Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; and the Department of Neurology (Dr. Rinne), University of Turku, Turku, Finland. Neurology August 1994 vol. 44 no. 8 1374 ]

“Because of common ancestral founder mutations, genetic diseases are frequent in the Mennonites and Amish-Mennonites. However, unlike many genetic disorders that are increased in ethnic groups, dystonia in the Mennonites and Amish-Mennonites is typically associated with an autosomal dominant disorder, DYT6. DYT6 was first mapped, and then identified in three Amish-Mennonite families.

Nonetheless, there is a heterogeneous etiology for dystonia in the Amish-Mennonites: the relative contribution of DYT6 is not known, other presumed dominant but not yet identified dystonia genes contribute, as do recessive metabolic disorders. The approach to discerning the etiology of dystonia in these groups is therefore similar to that of other forms of dystonia and relies heavily on careful evaluation of the history, examination, and clinical phenotype.

The geographic origins of Amish-Mennonite and Mennonite groups reveals a window into understanding founder mutations and focus on DYT6 dystonia, an autosomal dominant mixed phenotype primary dystonia. There are other etiologies for primary dystonia in the Amish-Mennonites including DYT1, unknown primary etiologies, as well as etiologies for secondary dystonia which may be increased in Mennonites and Amish-Mennonites due to the founder effects in these groups, intermingling with carrier groups. Secondary dystonia from head trauma and possibly focal body injuries occurs in football athletes.

A documented case report of football athlete dystonia, in an adult who played thr;oughout life and part of college, who had sustained multiple ‘head dings’, concussions and heat exhaustion revealed the following symptoms and signs: intermittant generalized fasiculations, generalized muscle cramps including the face torso and extremities, spinal stenosis, left leg contracted into permanently genu flexed position, torso torsion at the waist at 45*, intermittent muscle pain to name a few and immobility except for a few short steps.

In terms of secondary Dystonias, which can be caused by trauma, other disorders, conditions or diseases, the numbers can be propelled into the millions. [Surgeons Trying Pacemaker Procedure For The Brain, Doctors Find Deep Brain Stimulation Can Help Patients Deal With Neurological Disorder, ABC 7 News, Denver, Apr 14, 2010] [Genetic Research Leads to New Discovery in Understanding Rare Neurological Disorder February 1, 2009, Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia] [Dystonia in Amish-Mennonite and Mennonite Families by R. Saunders-Pullman Encyclopedia of Movement Disorders2010, Pages 375–377 Albert Einstein College of Medicine, Beth Israel Medical Center, New York, NY, USA]

Key Words: Amish; Amish-Mennonite; Autosomal recessive dystonia; DYT6 genetic disorder
[Dystonia in Amish-Mennonite and Mennonite Families by R. Saunders-Pullman Encyclopedia of Movement Disorders2010, Pages 375–377 Albert Einstein College of Medicine, Beth Israel Medical Center, New York, NY, USA]

“Genetic Research Lead to New Discovery in Understanding Rare Neurological Disorder February 1, 2009 – A study led by Laurie Ozelius, PhD at Mount Sinai School of Medicine has identified a gene associated with the development of primary torsion dystonia, also known as DYT6 dystonia. With funding provided by the Dystonia Medical Research Foundation (DMRF), Dr. Ozelius and her colleagues have found that mutations in the THAP1 gene cause DYT6 dystonia in Amish-Mennonite families, as well as in other ethnic groups.

Fuchs et al reported the discovery of a mutation in the THAP1 gene in three Amish-Mennonite families with mixed-onset primary torsion dystonia (also known as DYT6 dystonia). Another mutation in a German family with primary torsion dystonia suggests that THAP1 mutations also cause dystonia in other ancestry groups. We demonstrate that the missense mutation impairs DNA binding, suggesting that transcriptional dysregulation may contribute to the phenotype of DYT6 dystonia. [Fuchs T1, Gavarini S, Saunders-Pullman R, Raymond D, Ehrlich ME, Bressman SB, Ozelius LJ.Author information 1Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USANat Genet. 2009 Mar;41(3):286-8]

Dystonia is a neurological movement disorder characterized by sustained, uncontrolled muscle contractions and spasms. There are multiple forms affecting men, women, and children of all ages and backgrounds. More than 300,000 people in Canada and the United States are estimated to have some form of primary dystonia. In terms of secondary dystonias, which can be caused by trauma, other disorders, conditions or diseases, the numbers can be propelled into the millions. There is no cure.

Since the pathogenic mechanisms of primary torsion dystonias are very poorly understood any new information about genetic causes of these diseases is desperately needed to facilitate new studies toward the understanding of those mechanisms. The newly discovered DYT6 gene and protein can now be used as drug discovery targets.

“Primary torsion dystonia are rare and devastating diseases,” explains the Foundation’s Science Officer, Dr. Jan Teller. “This is the second gene identified for this type of dystonia. Its discovery will greatly contribute to our knowledge about molecular mechanism of all the dystonias.”

“We are greatly excited about Dr. Ozelius’s findings, as they will help us to better understand the many different factors responsible for this puzzling and disabling disorder,” says Dr. Mahlon DeLong, Scientific Director of the Foundation. “Dr. Ozelius has been a pioneer in genetic research on dystonia and we are grateful for her unwavering commitment to this and the broader dystonia community.”

“I am grateful to the Foundation for their support of this research,” adds Dr. Ozelius. “The DMRF has supported gene identification studies throughout its history and has been a leader in recognizing that these studies represent an important first step leading to molecular insights into the disease.”

The Dystonia Medical Research Foundation is dedicated to advancing research for more treatments and ultimately a cure, promoting awareness and education, and supporting the needs and well being of affected individuals and families. DMRF works in partnership with the Dystonia Medical Research Foundation in the United States to ensure funding of the best and most relevant dystonia medical research worldwide.
[Genetic Research Leads to New Discovery in Understanding Rare Neurological Disorder]

DYSTONIA COALITION:
Administrative Center Location Natural History Study Blepharospasm Tools
Emory University Atlanta, GA
Project Planning Centers Location Natural History Study Blepharospasm Tools
James Madison University Harrisonburg, VA
NIH/NINDS Bethesda, MD
Università delgi Studi di Bari “Aldo Moro” Bari, Italy
Universitá Degli Studi Di Roma “La Sapienza” Rome, Italy
Washington University at St. Louis St. Louis, MO
US Clinical Centers Location Natural History Study Blepharospasm Tools
Baylor College of Medicine Houston, TX
Beth Israel Medical Center New York, NY
Beth Israel Deaconess Boston, MA
Booth Gardner Parkinson’s Kirkland, WA
Johns Hopkins University Baltimore, MD
Lahey Clinic Burlington, MA
Mount Sinai School of Medicine New York, NY
Parkinson’s and Movement Disorders Institute Fountain Valley, CA
Rush University Chicago, IL
Sanford Health – Fargo Fargo, ND
University of California, San Diego La Jolla, CA
University of Chicago Chicago, IL
University of Cincinnati Cincinnati, OH
University of Colorado Aurora, CO
University of Florida Gainesville, FL
University of Iowa Iowa City, IA
University of Maryland Baltimore, MD
University of New Mexico Albuquerque, NM
University of Rochester Rochester, NY
University of Tennessee Memphis, TN
University of Texas Southwestern Dallas, TX
Virginia Commonwealth University Richmond, VA
Wake Forest Health Sciences Winston-Salem, NC
Australian Clinical Centers Location Natural History Study Blepharospasm Tools
Westmead Hospital Westmead, New South Wales, Australia
Canadian Clinical Centers Location Natural History Study Blepharospasm Tools
Centre hospitalier de l’Université de Montréal Montréal, Quebec, Canada
University of Alberta Edmonton, Alberta, Canada
University of Toronto Toronto, Ontario, Canada
European Clinical Centers Location Natural History Study Blepharospasm Tools
Université Pierre et Marie Curie-Paris 6, Groupe Hospitalier Pitié-Salpêtrière Paris, France
University College London – Institute of Neurology London, United Kingdom
University of Lübeck Lübeck, Germany
Partnering Groups Location
Data Management and Coordinating Center (DMCC); University of South Florida Tampa, FL
NINDS Repository at Coriell Camden, NJ
Dystonia Study Group (DSG) Chicago, IL

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