DYT1 Generalised Dystonia

Also known as: DYT1 early-onset primary or torsion dystonia; Oppenheim’s dystonia

DYT1 generalised dystonia is a neurological movement disorder that is characterised by involuntary, sustained, twisting muscle spasms. Onset is typically in childhood or adolescence and only rarely in adulthood.  Symptoms tend to start in one limb then often spread to other limbs and adjoining body areas leading to progressive disability.

DYT1 generalised dystonia is an autosomal dominant condition that is expressed with reduced penetrance. It is one of the less common forms of primary dystonia and the only type that is more prevalent among Ashkenazi Jews relative to the general population.

Presentation

Often dystonia is initially apparent with specific actions such as a notable change in walking or writing. Age of onset and severity of the disorder varies considerably (even within the same family), however, common signs and symptoms include:

  • Turning in of a foot and/or leg and/or arm.
  • Muscle spasm with or without pain.
  • Twisted postures of the limbs or trunk.
  • Abnormal fixed postures of the limbs or trunk.
  • Rapid, sometimes rhythmic, jerking movements.
  • Unusual walking with bending and twisting of the torso.
  • Symptoms often become worse with stress and tiredness, however, usually disappear during sleep.

Symptoms tend to start in one limb then often spread to other limbs and adjoining body areas leading to progressive, more generalised disability, which may occur over several years. Overall 60-70% individuals have progression to generalized or multifocal dystonia however for some patients the symptoms remain focal and very benign.

Please click on the titles to open and close the following information sections.

  • DYT1 generalized dystonia is caused by a mutation in the TOR1A gene located at chromosome 9q34.11 that encodes for the protein torsin-1A.
  • The mutation is thought to affect functioning of the basal ganglia, however, the exact way in which these structures malfunction in dystonia is not currently clear.
  • Though dominant in inheritance, with the reduced penetrance it is estimated that only around 30% of individuals with the mutation appear to develop symptoms.
  • The carrier frequency in the Ashkenazi Jewish (AJ) population is approximately 1 in 1000 to 1 in 3000.
  • Given the reduced penetrance, the disorder incidence is estimated to be between 1 in 3000 to 1 in 9000 – which is approximately 3-5 times higher than in the general population.
  • DYT1 generalised dystonia is estimated to account for 20-50% of early onset dystonia in the general population and approximately 80-90% in people of AJ descent.

Gene Specific:

  • Clinical diagnosis can be confirmed by genetic testing of the TOR1A gene.
  • A single mutation (a 3-base-pair GAG deletion) is responsible for over 99% of cases of DYT1 generalised dystonia among Ashkenazi Jews.

Other supporting evidence:

  • Brain CT brain and routine MRI are normal.
  • No other abnormalities on neurological examination (except tremor).
  • No history of known cause of acquired (secondary) dystonia e.g. cerebral trauma, exposure to neuroleptic medications etc.

No known cure for DYT1 generalised dystonia at this time, however, various supportive and symptomatic treatments are available.

Oral medications are usually tried first, either alone or in combination:

  • Levodopa trial to identify dopa-responsive dystonia.
  • Anti-cholinergic drug may help to control muscle spasm or tremor.
  • Second line treatments may include clonazepam or tetrabenazine and baclofen.

Botulinum toxin injections for treatment of focal symptoms can be used in conjunction with oral medications.

Surgical intervention may be suitable for some, usually more severely affected, cases. Deep brain stimulation (DBS) of the globus pallidus interna can provide sustained benefit for affected individuals and can help prevent contractures of the joints and deformities of the spine sometimes associated with disorder development.

Family members should be offered genetic counseling and testing as appropriate. Carrier testing and pre-natal testing is available for this condition.

  • Disorder progression is variable and is partly influenced by age of onset and body area where the symptoms begin.
  • Where symptoms develop, the younger the age of onset, the more likely the symptoms will begin in a lower limb, spread upwards and possibly become generalized.
  • When symptoms begin in the arm or neck, onset tends to be slightly later and the progression to other body areas may be less likely.
  • If symptoms have not developed by age 30, they are much less likely to do so later in life.
  • Symptom progression often plateaus after a few years, after which further significant deterioration is unusual.
  • Typically life expectancy is unaffected.
  • For children exhibiting features of DYT1 generalised dystonia, initial referral would usually be to a paediatrician; and referral to a neurologist for adults. With Jewish patients, it is important to note ancestry and higher prevalence of this disorder in the Jewish population.
  • For patients that have received a positive diagnosis:
    • On-going management is usually under the care of neurologists.
    • Families may benefit from referral to a clinical genetics department to establish carrier status in other family members as appropriate.
The Dystonia Society – TDS

This UK-wide charity provides a wide range of services, advice and information for anyone affected by dystonia. It aims to facilitate access to the most appropriate treatment, support and information available; to raise awareness of the condition; and to promote research. Their website includes information about all types of dystonia, living with the condition, support services, research, and links to additional resources. This site also contains a forum for support and information.
Helpline number: 0845 458 6322 or 020 7793 3658; Office number: 0845 458 6211

The TDS report ‘Dystonia: A Guide to Best Practice for Health and Social Care Professionals’ provides a wealth of valuable, up-to-date information covering all dystonias (including generalised dystonia) – click on the report title to view.

Dystonia Medical Research Foundation (USA)

The DMRF is a USA-based organisation that provides support and information to those affected by dystonia and is deeply involved in dystonia-related research initiatives. Their website provides information about all types of dystonia, past and current research, treatment, support, and activities to raise awareness and progress understanding and treatment. It also has a sister organisation in Canada – Dystonia Medical Research Foundation Canada

European Dystonia Federation (Europe)

The EDF is a collaborative effort by European dystonia groups to raise the profile of dystonia and influence health and government policies at a European level. Their website includes links to member organisations, the dystonia international patient registry and other resources.

GeneReviews: www.ncbi.nlm.nih.gov/books/NBK1492

OMIM: #128100

Written by Dr Jacky Megitt, Jnetics researcher
Approved by: Professor Patricia Limousine, Professor in Clinical Neurology and Honorary Consultant Neurologist, UCL Institute of Neurology, Queens Square
Last review: 20.1.2015

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