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Disease
Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia may affect a single body area or be generalized throughout multiple muscle groups. Although there are many different forms of dystonia and the symptoms may appear quite different at first site, the element that all forms share is the repetitive, patterned and involuntary muscle contraction.

Dystonia is a chronic disorder, but by and large it does not impact on cognition, intelligence, or shorten a person’s life span.
  Locus symbol Phenotype Mode of inheritance linkage Gene
Isolated
dystonias
DYT1 Early-onset primary torsion dystonia Autosomal dominant 9q34 TOR1A
DYT2 Early-onset primary dystonia with prominent
cranio-cervical involvement
Autosomal recessive 1p35 HPCA
DYT4 Whispering Dysphonia Autosomal dominant 19p13.3 TUBB4A
DYT6 Adult-onset torsion dystonia with prominent
craniocervical and laryngeal involvement
Autosomal dominant 8p11.21 THAP1
DYT7 Adult-onset primary cervical dystonia dystonia Autosomal dominant 18p unknown
DYT13 Early-onset torsion dystonia Autosomal dominant 1p36.13-p36.32 unknown
DYT17 Primary focal dystonia with progression Autosomal recessive 20p11.22-q13.12 unknown
DYT21 Adult –onset mixed dystonia with generalization Autosomal dominant 2q14.3-q21.3 unknown
DYT23 Adult onset focal cervical dystonia Autosomal dominant 9q34.13 CIZ1
DYT24 Craniocervical dystonia (often tremulous) +/- upper
limb tremor
Autosomal dominant 11p14.2 ANO3
DYT25 Adult onset focal /segmental cervical dystonia Autosomal dominant 18p11.21 GNAL
Paroxysmal
dystonias
DYT8 Paroxysmal non-kinesigenic dyskinesia (PNKD) Autosomal dominant 2q35 PNKD1/ MR1
DYT10 Paroxysmal kinesigenic dyskinesia with wide
phenotypic variability, including epilepsy, migaine
and intermittent torticollis
Autosomal dominant 16p11.2 PRRT2
DYT18
(DYT9)
Paroxysmal exercise-induced dyskinesia +/- epilepsy Autosomal dominant 1p34.2 SLC2A1
DYT20 Paroxysmal non-kinesigenic dyskinesia 2 Autosomal dominant 2q31 unknown
Combined
dystonias
DYT3 LUBAG, early –onset dystonia parkinsonism x-linked Xq13.1 TAF1
DYT5a Progressive DOPA-responsive dystonia with
diurnal variation, DRD, Segawa-Syndrom
Autosomal dominant 14q22.1-q22.2 GCH1
DYT5b Akinetic rigid syndrome with Dopa-responsive
Dystonia or complex encephalopathy
Autosomal rezessive 11.p15.5 TH
DYT11 Myoclonic dystonia (often with alcohol
responsiveness)
Autosomal dominant 7q21.3 SGCE
DYT12 Rapid onset dystonia parkinsonism and
alternating hemiplegia in childhood
Autosomal dominant 19q12-q13.2 ATP1A3
DYT15 Myoclonic dystonia with alcohol responsiveness Autosomal dominant 18p11 unknown
DYT16 Early-onset dystonia parkinsonism Autosomal recessive 2q31.3 PRKRA

Table 1: Genetic forms of Dystonia
Dystonia affects men, women, and children of all ages and backgrounds. Estimates suggest that no less than 300,000 people in Europe are affected.
Dystonia causes varying degrees of disability and pain, from mild to severe. There is presently no cure, but multiple treatment options exist and scientists around the world are actively pursuing research toward new therapies.

Cause

Understanding the cause(s) of dystonia is likely to lead to new and better treatments, but this is not a simple task. Scientists have not yet identified the precise biochemical and physiological processes in the body that eventually result in the symptoms.

While we do know that dystonia can occur, in rare cases, as a consequence of brain trauma, as a side effect of certain medications, or can be caused by mutated genes, in the vast majority of cases, the cause is still completely unknown. And even if we may say that a mutated gene gene or physical trauma contributes to the development dystonia, this do not address the question what happens inside the body to produce the symptoms.

Classification of the dystonias

Dystonia can be classified along different “axes”, for example according to the predominat clinical characteristics, or according to etiology. None of those classification schemes is perfect.

Traditionally, dystonias have often be grouped into “primary” (or “idiopathic”) dystonias, “dystonia-plus”- syndromes, heredo-degenerative, secondary or paroxysmal (Albanese 2006 and Table 2).
Wilson's disease

Parkinsonian syndromes
  • Parkinson's disease
  • Juvenile parkinsonism (PARKIN mutations)
  • Multisystem atrophy
  • Corticobasal degeneration
  • Progressive supranuclear palsy
Globus pallidus degeneration

Pantothenate kinase deficiency due to PANK2 mutations

Familial basal ganglia calcification

Huntingston's disease

Spinocerebellar degenerations

Lysosomal storage disorders
  • Dystonic lipidosis
  • Ceroid lipofuscinosis
  • Metachromatic leukodystrophy
  • GM1 and GM2 gangliosidosis
  • Niemann-Pick disease type C
  • Krabbe's disease
  • Pelizaeus-Merzbacher disease
Organic aminoacidurias
  • Glutaric aciduria
  • Homocysteinuria
  • Hartnup's disease
  • Methylmalonic aciduria
Mitochondrial disorders
  • Leigh's disease
  • Leber's plus dystonia
  • X-linked dystonia-deafness
Neuroacanthocytosis

Lesch-Nyhan syndrome

Ataxia-teleangiectasia

Table 2
 
The word “primary” describes a case in which dystonia is the only neurologic feature (with the exception of tremor). Primary dystonias include genetic forms (in some of which, such as in DYT1 dystonia, a gene has been identified, see Table 1) and forms for which a cause is unknown (such as most focal dystonias).
By cause (etiology)
  • Primary (or idiopathic): dystonia is the only clinical sign and there is no identifiable exogenous cause or other inherited or degenerative disease. Example: DYT-1 dystonia Dystonia plus: dystonia is a prominent sign, but is associated with another movement disorder. There is no evidence of neurodegeneration. Example: Myoclonus-dystonia (DYT-11)
  • Heredo-degenerative: dystonia is a prominent sign, amongst other neurological features, of a heredo-degenerative disorder. Example: Wilson's disease
  • Secondary: dystonia is a symptom of an identified neurological condition, such as a focal brain lesion, exposure to drugs or chemicals. Examples: dystonia due to a brain tumor, off-period dystonia in Parkinson's disease
  • Paroxysmal: dystonia occurs in brief episodes with normalcy in between. These disorders are classified as idiopathic (often familial although sporadic cases also occur) and symptomatic due to a variety of causes. Three main forms are known depending on the triggering factor. In paroxysmal kinesigenic dyskinesia (PKD; DYT-9) attacks are induced by sudden movement; in paroxysmal exercise induced dystonia (PED) by exercise such as walking or swimming, and in the non-kinesigenic form (PNKD; DYT-8) by alcohol, coffee, tea, etc. A complicated familial form with PNKD and spasticity (DYT-10) has also been described
By age at onset
  • Early onset (variably defined as <=20-30 years): usually starts in a leg or arm and frequently progresses to involve other limbs and the trunk
  • Late onset: usually starts in the neck (including the larynx), the cranial muscles or one arm. Tends to remain localized with restricted progression to adjacent muscles
By distribution
  • Focal: single body region (e.g. writer's cramp, blepharopasm)
  • Segmental: contiguous body regions (e.g. cranial and cervical, cervical and upper limb)
  • Multifocal: non-contiguous body regions (e.g. upper and lower limb, cranial and upper limb)
  • Generalised: both legs and at least one other body region (usually one or both arms)
  • Hemidystonia: half of the body (usually secondary to a structural lesion in the contralateral basal ganglia)
Table 3: Tarsy and Simon
In “secondary” dystonias, on the other hand, are cases that can be clearly attributed to a recognizable cause, such as drug exposure, brain trauma, or anotheris (often neurodegenerative) disease (Table 3, Tarsy and Simon),

The “dystonia-plus” syndromes are genetic forms of dystonia, in which the main symptom, dystonia, occurs together with some specific features, such as exquisite dopa-responsiveness in the dopa-responsive dystonias (DRD), or rapid myoclonic jerks in myoclonus-dystonia syndromes.

A problem of this classification is that it does not clearly distinguish between etiologic and clinical criteria for classification. A new classification was therefore suggested, that describes the dystonias as either “isolated” (dystonia as the only symptom of disease) or “combined” (dystonia plus additional movement abnormalities), irrespective of its cause, which is classified in a second “axis”, as inherited or acquired (Albanese et al, Movement Disorders, 2013).

How is Dystonia diagnosed?

At this time, there is no single test to confirm the diagnosis of dystonia. Instead, the diagnosis rests in a physician’s ability to observe symptoms of dystonia and obtain a thorough patient history. In order to correctly diagnose dystonia, doctors must be able to recognize the physical signs and be familiar with the symptoms. In certain instances, tests may be ordered to rule out other conditions or disorders. The kind of physician who is typically in the best position to diagnose dystonia is a movement disorder neurologist.

The dystonia diagnostic process may include:

  • Patient history
  • Family history
  • Laboratory studies such as blood and urine tests, and analysis of cerebrospinal fluid
  • Electrical recording techniques, such as electromyography (EMG) or electroencephalography (EEG)
  • Genetic testing for specific forms of dystonia
  • Other tests and screenings intended to rule out other conditions or disorders

Symptoms

Dystonia causes a wide variety of symptoms, and each person with dystonia is unique. People with all forms of dystonia have been able to become educated, work, remain independent and active, date and marry, enjoy children and family, and live productive fulfilled lives. Individuals may have to adjust activities and lifestyle to incorporate dystonia, but having this disorder does not define who you are.

Most cases of primary dystonia (both generalized and focal forms) will usually stabilize with respect to symptom severity within five years of onset. However, symptoms may still fluctuate. For example, stressful situations may make symptoms temporarily worse.

Currently, no medication or therapy can prevent progression from happening. Prompt diagnosis and treatment can often minimize the impact of symptoms and improve or maintain a person’s ability to function in everyday activities.

Treatments

Although there is presently no cure for dystonia, multiple treatment options are available. Because every person with dystonia is unique, treatment must be highly customized to the need of the individual. No single strategy will be appropriate for every case. The purpose of treatment for dystonia is to help lessen the symptoms of muscle spasms, pain, and awkward postures. The ultimate goal is to improve the quality of life and help to function with the fewest side effects possible. In most cases, the most appropriate kind of doctor to treat dystonia is a movement disorder neurologist. Establishing a satisfactory treatment plan requires open communication and patience on the part of both the affected individual and the physician.

The first step in treating dystonia is to determine as much as possible about the underlying cause. When a person is first diagnosed with dystonia, a movement disorder specialist may recommend non-drug approaches prior to or in conjunction with traditional treatments such as oral medications. These non-drug approaches may include physical and occupational therapy as well as speech or voice therapy if appropriate. These approaches empower the individual with techniques to help achieve greater awareness and control over the body.

There are many medications that have been shown to improve dystonia. No single drug works for every individual, and several trials may be necessary to determine which is most appropriate for any given patient. Working with your physician to determine the drugs best suited for your case may be challenging, but finding the right drug(s) can result in a dramatic improvement of symptoms.

There are several categories of medications used in the treatment of dystonia. They include: anticholinergics, benzodiazepines, baclofen, dopaminergic and dopamine-depleting agents. The introduction of botulinum toxin as a therapeutic tool in the late 1980s revolutionized the treatment of focal and segemental dystonias by offering a new, localized method to significantly relieve symptoms for many people. Botulinum toxin, a bacterial toxin, is injected into specific muscles where it acts to relax the muscles and reduce excessive muscle contractions.

Surgical treatments for dystonia may be an option for individuals whose symptoms do not respond to oral medications or botulinum toxin injections. Recently, deep brain stimulation (DBS) has shown highly promising results in those cases. Researchers are actively refining current techniques and collecting information about which patients may benefit the most from surgical treatments.