Primary torsion dystonia (PTD) is a genetically heterogeneous, isolated form of dystonia.
The most important signs by which the patient presents are as follows: difficulty in walking, foot drag, cramps, contortions, difficulty in grasping objects, speech difficulty, physical deformities and muscle contractions.
Some patients may also present with the following signs: twisting of the body, jerking of the head, tremors of the hands or feet and arms or legs and difficulty in writing. Dystonic movements intensify with action. Movements of primary dystonia occur only with specific actions and not at rest. If the disease condition continues to worsen, dystonic movements will be seen at rest as well and the patient eventually develops a sustained posturing .
Dystonia tremors which are irregular, rhythmic contractions may be observed in some patients as well. Facial muscles which are affected manifest patterns of sustained contractions on the forehead, eyelids and lower face .
Limbs which are affected may show an increased intensity of contractions because of specific voluntary tasks which may cause it. Writing of an individual is affected when the upper extremities are affected. The pattern of muscle contractions in dystonia is consistent and predictable. However, with changing position and tasks, involuntary movements may vary. Other physical and neurologic findings may be present in addition to dystonia.
- Short Arm
A genome-wide search performed in the family identified a novel PTD locus (DYT13) within a 22-cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 (theta 0) between the disease and marker D1S2667. [ncbi.nlm.nih.gov]
Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 between the disease and marker D1S2667. [discovery.ucl.ac.uk]
Abnormal TDTs were found in 36 of 37 (97.3%) cervical dystonia, 12 of 14 (85.7%) writer's cramp, 8 of 9 (88.8%) blepharospasm, 10 of 11 (90.1%) spasmodic dysphonia patients and 5 of 8 (62.5%) musicians. [ncbi.nlm.nih.gov]
Defazio G, Matarin M, Peckham EL, et al.: The TOR1A polymorphism rs1182 and the risk of spread in primary blepharospasm. Mov Disord 2009, 24:613–616. CrossRef PubMed Google Scholar 36. [link.springer.com]
Originally published in the Benign Essential Blepharospasm Research Foundation Newsletter, Volume 28, Number 5, pages 6, 13 (2009) Home Blepharospasm index Top of this page [blepharospasm.org]
Blepharospasm is the second most common focal dystonia. It causes involuntary contraction of the eyelids and can hold them closed for indefinite periods of time. [cbc.arizona.edu]
To evaluate the contribution of these genetic loci to other families with familial "non-DYT1" dystonia five large families with dystonia were studied using genetic markers spanning the DYT6 and DYT7 regions. [ncbi.nlm.nih.gov]
A few cases had additional voice tremor and/or postural arm tremor. The GAG deletion in the DYT1 gene was excluded in the index case. [ncbi.nlm.nih.gov]
Dystonia is the third most common movement disorder after Parkinson's disease and Tremor. [books.google.com]
PTD is manifested as an isolated movement disorder without clinical evidence of cognitive, sensory or cerebellar deficit or any other symptoms except tremor [ 1, 2 ]. [omicsonline.org]
- Involuntary Movements
We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement. 2004 Movement Disorder Society. [ncbi.nlm.nih.gov]
This syndrome causes involuntary movements that usual start in the lips, tongue or face. The side effects can become a permanent disability. [krafchick.com]
While chorea is the most common involuntary movement in this condition (rapid irregular random jerky movements that may affect face, arm, legs or trunk), dystonia and parkinsonism may also be present. [dystonia-parkinson.org]
movements, occurring spontaneously at rest, precipitated by caffeine, alcohol, stress, lasting from minutes to hours and occurring several times each day DYT-21 2q14.3-q21.3 Uncategorized Autosomal Dominant [cmdg.org]
movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. [icdlist.com]
- Extrapyramidal Symptoms
Extrapyramidal Symptoms Associated With Cyclic Antidepressant Treatment: A Review Of The Literature And Consolidating Hypotheses. J Clin Psychopharmacol 1997; 17: 377 - 389. 36. Jarecke CR, Reid PJ. [ispub.com]
- Axial Dystonia
dystonia (33 %), and in cervical dystonia secondary to stroke (20 %). 8. 9 Dystonia has also been associated with substance misuse (13 % of patients), especially in alcohol responsive myoclonic-dystonia. 7 No studies have examined psychiatric morbidity [ispub.com]
The following should be considered when the history and physical findings of the patient suggest only dystonia and when the age of onset is younger than 26 years: DYT1 with genetic counselling. If the patient tests negative for DYT1, a levodopa trial must be considered. If the patient does not respond even to a levodopa trial, it is advised to perform a MRI and a ceruloplasmin test. A slit-lamp examination can also be done.
If the age of onset is older than 26 years, a MRI and serum ceruloplasmin must be done. The patient must also be assessed for a history of exposure to a dopamine-blocking agent in case of other causes. If there are metabolic or neurodegenerative causes, the following must be done in addition to the above: EEG, CSF analysis, electromyography, chromosomal analysis, antiphospholipid antibody testing, and genetic testing for Huntington ’s disease, mitochondrial diseases, alpha-fetoprotein test and skin, muscle and nerve biopsy .
Treatment available for dystonias at the moment, are basically symptomatic and palliative. No curative treatment is available at the moment. Only the intensity of the disease symptoms can be controlled which can improve the quality of life of the patients. The intensity can be controlled with the help of oral medications, intramuscular or subcutaneous boutulinum toxin injections and physiotherapy or rehabilitation .
Surgical mode of treatment is indicated in those patients in whom the symptoms are severe and in whom drug therapy fails because of drug reaction. Thalmotomy and bilateral pallidotomy are the preferred surgeries for dystonia .
Dystonia has historically been classified into 2 main etiologic groups: primary (idiopathic) and secondary (symptomatic). Idiopathic dystonia was distinguished from the symptomatic dystonias by its lack of a known cause and the absence of consistent brain pathology. However, it has become clear that idiopathic dystonia consists of a group of clinical syndromes that are likely to have a genetic basis .
Primary dystonia is a genetically heterogeneous disease. Hence, the disorder could be hereditary or may be birth-related. There is a possibility of Dystonia being caused due to physical trauma, infection, poisoning or as a reaction to pharmaceutical drugs such as neuroleptics. In hereditary cases, several causative genes have been identified but their genetic bases still remain elusive.
Primary Torsion Dystonia can be due to a monogenic inheritance and many gene loci have been discovered for the autosomal dominant (DYT1/TOR1A; DYT6/THAP1; DYT4/TUBB4a; DYT7; DYT13; DYT21; DYT23/CIZ1; DYT24/ANO3; DYT25/GNAL) and recessive (DYT2; DYT17) forms   . In late-onset sporadic cases, the involvement of genetic and environmental factors play an important role .
The relative prevalence and distribution of PTD is difficult to estimate because of the variation in its expression and the tendency for mild cases to go undiagnosed. Several large studies have shown that early-onset primary torsion dystonia is 5-10 times more common in Ashkenazi Jews than in people who were not Jewish or in Jewish individuals not of Ashkenazi heritage. Subsequent studies have found a wide range in the prevalence of dystonia from 6-7,320 persons per million population .
Late-onset focal primary dystonia was 10 times more common than early-onset generalized primary torsion dystonia . Childhood- and adolescent-onset primary dystonia is more common in Jews of Eastern European or Ashkenazi ancestry than in other groups. Segmental and focal dystonias are more prevalent in the female population .
The precise cause is not known however, the most probable cause for Primary Torsion Dystonia is the result of a genetic mutation. Several of the hereditary primary dystonias implicate altered synaptic communication within the basal ganglia. For example, torsin A which is encoded by the DYT1 (early onset) gene (also known as TOR1A), is expressed at high levels in human dopaminergic neurons. Most cases are associated with asingle mutation in the DYT1 gene, a three base-pair deletion (ΔGAG) that leads to the loss of a glutamicacid residue in the carboxy-terminal region of torsin A  .
Torsin A is located predominantly within the lumen of the endoplasmic reticulum and nuclear envelope. It is a member of the family of ATPases that are associated with a variety of cellular activities (AAA +) and it is therefore likely to mediate ATP-dependent conformational remodelling reactions involving substrate proteins or protein complexes. It has been proven that torsin A regulates the organization of nuclear envelope and endoplasmic reticulum compartments with respect to the cytoskeleton and participates in the processing of proteins through the secretory pathway .
Torsin A binds to lamina-associated polypeptide 1 (LAP1) in the inner nuclear envelope and to a related protein in the endoplasmic reticulum. Recent studies suggest that the ΔGAG deletion results in a loss of torsin A activity. Because AAA + proteins typically function as homo-oligomericcomplexes — usually hexamers — the ΔGAGmutant protein might also exert a dominant-negative effectand decrease wild-type torsinA activity in heterozygous DYT1 patients .
Primary Torsion Dystonia may be focal, segmental, and multifocal or generalized depending on the anatomic site involved.
Since it has a genetic basis, there is no method for prevention available yet.
Dystonias are heterogeneous hyperkinetic neurological movement disorders where there are sustained muscle contractions that cause twisting and repetitive movements and abnormal postures. In 1908, Schwalbe first described primary, or idiopathic, torsion dystonia in a Jewish family. In 1911, Oppenheim termed this dystonia as musculorum deformans (DMD). In earlier times, dystonia was attributed as a symptom of hysteria, however primary torsion dystonia eventually became established to be a neurological disease with genetic basis.
Treatment for Primary Torsion Dystonia (PTD) is usually palliative. Primary Torsion Dystonia also termed as Idiopathic Dystonia, refers to pure primary forms characterized by dystonia alone. It can further be divided based on the age of onset and the distribution of the dystonia which can be focal, segmental or generalized. Early onset dystonias are commonly seen in people who suffer from it because of hereditary factors; however, late onset Primary Torsion Dystonia is usually sporadic and tends to remain focal or segmental in distribution .
Primary Torsion Dystonia is a neurological condition which is generally hereditary or birth-related. The cause is not clearly known. However, it is postulated to be caused due to genetic mutation. It is more prevalent amongst Ashkenazi Jews and mostly seen in females than in males. It is a progressive disease with a poor outcome, however in this type of dystonia there is no damage to the brain seen. It is characterized by repetitive twisting movements and sustained muscle contraction which can lead to abnormal postures of the body.
If a person tests positive for DYT1, then the person is said to be suffering from Primary Torsion Dystonia (PTD). Other tests conducted to diagnose this disease includes, MRI and serum ceruloplasmin. People suffering from this illness usually present with difficulty in walking, difficulty to hold on to anything (because of which the writing of a person can also suffer), cramps, physical deformities and muscle contractions .
There is no cure for this disease however the standard of living of these patients can be improved by alleviating the symptoms by administering oral medications. For patients who develop a reaction to the drug administered and those who do not respond to oral medication, surgery is an option that is usually taken into consideration. However, resorting to physiotherapy, rehabilitation and relaxation techniqueshelp improve the quality of life of the patient. Braces and assistive devices may help increase mobility, improve strength and prevent contractures from forming.
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