DYT-TOR1A

Other Names: DYT1; Early onset torsion dystonia; EOTD; Dystonia musculorum deformans 1; Early-onset primary dystonia; Oppenheim's dystonia; Idiopathic dystonia DYT1; Idiopathic torsion dystonia; Dystonia 1, torsion, autosomal dominant; DYT-TOR1A dystonia; Dystonia 1; DYT1 Early-Onset Isolated Dystonia; Early-Onset Torsion Dystonia; Early-onset generalized dystonia

Early-onset generalized dystonia is a neurologic movement disorder that usually begins in childhood or adolescence. This is the most common hereditary form of dystonia.

Cause

A small deletion in the DYT1 gene is the major cause of early-onset dystonia.

Inheritance

The genetic change responsible for early onset generalized dystonia is inherited in an autosomal dominant manner, though not everyone who inherits the genetic change will develop the condition. It is thought that only 30% of individuals who inherit the mutation will develop DYT1 dystonia. This is known as reduced penetrance Offspring of an affected individual or of an asymptomatic individual known to have a TOR1A pathogenic variant have a 50% chance of inheriting the variant and if inherited a 30% chance of developing clinical findings. Once the TOR1A c.907_909delGAG deletion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for DYT1 dystonia are possible.

Autosomal dominant pattern, a 50/50 chance.

Risk factors

Factors that are more specific to DYT1 early-onset isolated dystonia, including:

• Ashkenazi Jewish ancestry (although DYT1 dystonia can occur in individuals of any ethnicity);
• Onset in a limb before age 26 years;
• Two or more affected limbs.
• Family history of early-onset dystonia

Symptoms

Symptoms can vary greatly, even among members of the same family. For some, the disorder can cause significant disability, while others may experiences only isolated writer’s cramp. 80%-99% of people have these symptoms

• Gait disturbance(Abnormal gait)
• Hypertonia

30%-79% of people have these symptoms

• Abnormality of the voice(Voice abnormality)

1%-4% of people have these symptoms

• Incomplete penetrance

Diagnosis

Diagnosis/testing. The diagnosis of DYT1 dystonia is established in a proband by identification of a heterozygous TOR1A pathogenic variant on molecular genetic testing. A TOR1A three base-pair deletion, c.907_909delGAG, is identified in most affected individuals.

Treatment

Oral medications, either alone or in combination, are usually tried first, including anticholinergics, baclofen, benzodiazepines, and others. Botulinum toxin injections for treatment of focal symptoms can be used in conjunction with oral medications. If oral medications and botulinum toxin injections do not provide sufficient control of symptoms, surgery enabling deep-brain stimulation (DBS) of the globus pallidus interna (GPi) should be considered.

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Botulinum toxin type A(Brand name: Botox) Treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. Treatment of blepharospasm or strabismus associated with dystonia in adults

NIH genetic and rare disease info

• NIH info on DYT-TOR1A

DYT-TOR1A is a rare disease.

DYT-TOR1A Resources
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