DYT1 – Early-onset (Oppenheim) dystonia
- TOR1A gene (autosomal dominant)
- Early-onset (mean age of onset 13 years)
- Increased prevalence in Ashkenazi Jew
- Starts in a limb in most cases, and the spreads to other body parts
DYT2 – Autosomal recessive dystonia
- HPCA gene
- Early-onset
- Generalized or segmental primary torsion dystonia
DYT3 – X-linked Dystonia-Parkinsonism (Lubag disease)
- X-linked mutation in TAF1 gene
- Occurs almost exclusively in males from the Philippines
- Onset in 3rd – 4th decade with segmental or generalized dystonia, followed subsequently with Parkinsonism, which responds to Levodopa
DYT4 – Whispering dysphonia
- TUBB4A gene (autosomal dominant)
- Onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait.
DYT5 – Dopa-responsive dysphonia (Segawa syndrome; also DYT 14)
- Mutation in GCH1 (autosomal dominant) or TH gene (autosomal recessive) with incomplete penetrance)
- Onset in 1st decade of life, typically affecting the foot with focal action dystonia (can be mistaken for cerebral palsy) . Then evolves to generalized dystonia
- Better in the morning, worse later in the day
- Responds to Levodopa
DYT6 – Adolescent onset focal-onset dystonia in Mennonites
- THAP1 gene (autosomal dominant with incomplete penetrance)
- Onset in teenage years with focal or segmental dystonia involving the cranial or cervical areas. Rarely generalizes.
DYT7 – Adult onset focal dystonia
- Autosomal dominant mutation at 18pter-p11.32
- Adult onset of focal dystonia (cervical dystonia, writers cramp, dysphonia, or blepharospasm)
DYT8 – Paroxysmal nonkinesigenic dyskinesia (PNKD)
- PNKD gene (autosomal dominant)
- Onset in childhood/early teen; attacks tend to diminish in age
- Attacks of combinations of chorea, dystonia and ballism, most commonly involves the limbs, but can also affect the neck, face and trunk
- Triggered by emotional stress, fatigue, alcohol, caffeine or chocolate
- Can be preceded by an “aura” (tingling sensation or nausea)
- Attacks can last from minutes up to hours and even days
- Frequency up to 3 per day, with months of attack-free intervals
- Does not respond well to anti-seizure medication, but can respond to benzodiazepines and dopamine receptor blockers
DYT9 – Paroxysmal exertional dyskinesia (also called paroxysmal choreoathetosis with ataxia and spasticity)
- SCL2A1 gene (encodes GLUT1; autosomal dominant), associated with low CSF glucose
- Onset in childhood
- Paroxysmal episodes of unilateral or bilateral dystonia/chorea usually affecting the lower extremities, which affects walking; can also get episodic ataxia, parasthesias and double vision
- Develop a spastic paraplegia between attacks
- Attacks occur 1-5 times per month, and last 5-30 minutes
- Triggered exercise, stress and chocolate
- Responds to acetazolamide and benzodiazepines
DYT10 – Paroxysmal kinesigenic dyskinesia (PKD)
- PRRT2 gene (autosomal dominant)
- Onset predominantly in males in early teenage years
- Attacks of chorea, dystonia and ballism, which are triggered by sudden voluntary movements; most commonly involves the limbs, but can also affect the neck, face and trunk
- The attacks do not occur during sleep, nor do they result in LOC or amnesia, but there may be a preceding “aura” (tingling sensation or nausea)
- Attacks can be precipitated by stress or anxiety, startle, hyperventilation
- Attacks last seconds up to 5 minutes; occur with a frequency of 1 per month to 100 per day
- The number of attacks increase during puberty and decrease in the 3rd to 4th decade of life
- Responds well to carbamazepine; complete remission seen in > 90% of patients
DYT11 – Alcohol-responsive myoclonus-dystonia
- E-sarcoglycan gene (SGCE; autosomal dominant)
- Onset in 1st – 2nd decade
- Attacks when tend to affect the proximal upper extremity and neck, resulting in “shivering” myoclonic jerks. Focal dystonias may also occur
- Attacks occur at rest, and can be precipitated by stress, startle, caffeine, and reduced by consumption of alcohol.
- Co-morbidities mood disorders, OCD, and substance abuse can occur
- Responds to benzodiazepines, valproic acid and gamma-hydroxybutaric acic (GHB, sodium oxybate)
- Has a benign course
DYT12 – Rapid-onset dystonia-Parkinsonism
- ATP1A3 gene (autosomal dominant)
- Onset in adolescence or young adulthood; symptoms can be triggered initially by infection, physical stress (e.g. prolonged exercise, childbirth) or alcohol consumption
- Abrupt onset over hours to days of dystonia affecting the arms, legs and facial muscles, resulting in painful muscle cramps and spasms, and severe difficulty with speech and swallowing; also develop Parkinsonism, resulting in bradykinesia and postural instability
- Can also develop alternating hemiplegia of childhood
- Does not respond to Levodopa, but symptoms will stabilize after a month, though recovery is typically incomplete, and relapses can occur years later
DYT13 – Multifocal and segmental dystonia in Italians
- Autosomal dominant mutation in 1p36.32-p36.12.13
- Focal or segmental dystonia, affecting the cranial-cervical areas and upper limbs; mild course
DYT15 – Myoclonic-dystonia (not linked to SGCE mutations)
- Tremor or rapid jerky movements resembling myoclonus starting in the first or second decade
- Incomplete penetrance and variable response to alcohol
DYT16 – Dystonia-Parkinsonism syndrome
- Autosomal recessive mutation in PRKRA
- Progressive, generalized, early-onset dystonia with axial muscle involvement, oromandibular dystonia (sardonic smile), laryngeal dystonia and, in some cases, Parkinsonian features
DYT17 – Primary focal torsion dystonia
- Autosomal recessive mutation in 20p11.22-q13.12
- Found using a genome-wide search in a large consanguineous Lebanese family with three affected individuals
DYT18 – Paroxysmal exertion-induced dyskinesia/dystonia
- Autosomal dominant mutation in SLC2A1
- Episodic movement disorder, that may involved disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters in any cases, accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations
DYT19 – Episodic kinesigenic dyskinesia 2
- Likely synonymous with DYT10
DYT20 – Paroxysmal non-kinesigenic dyskinesia 2
- Autosomal dominant mutation in 2q31
- Characterized by attacks of involuntary movements, occurring spontaneously at rest, precipitated by caffeine, alcohol, stress, lasting from minutes to hours and occurring several times each day
DYT21 – Late-onset torsion dystonia
- Autosomal dominant mutation in 2q14.3-q21.3
DYT24 – Focal dystonia
- Autosomal dominant mutation in 11p14.2
- Cranio-cervical dystonia with prominent tremor
For more information and support/resources:
For additional information and support/resources:
- Dystonia Medical Research Foundation (Canada): http://www.dystoniacanada.org
- Dystonia Medical Research Foundation (US): https://dystonia-foundation.org
- Dystonia International Patient Registry (DIPR): http://www.dipregistry.com
- NIH Genetic Testing Registry: http://www.ncbi.nlm.nih.gov/gtr/
- NIH Hereditary Dystonia Overview: http://www.ncbi.nlm.nih.gov/books/NBK1155/