DYT1 Early-Onset Isolated Dystonia

Clinical characteristics: DYT1 early-onset isolated dystonia typically presents in childhood or adolescence and only on occasion in adulthood. Dystonic muscle contractions causing posturing or irregular tremor of a leg or arm are the most common presenting findings. Dystonia is usually first apparent with specific actions such as writing or walking. Over time, the contractions frequently (but not invariably) become evident with less specific actions and spread to other body regions. No other neurologic abnormalities are present. Disease severity varies considerably even within the same family. Isolated writer's cramp may be the only sign.

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.

Management: Treatment of manifestations: 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.

Prevention of secondary complications: Aggressive medical and surgical intervention to prevent contractures of the joints and deformities of the spine.

Surveillance: Follow up with a neurologist specializing in movement disorders several times a year.

Agents/circumstances to avoid: The extremities affected by dystonia should not be placed in a brace or cast, unless medically necessary, as this can worsen the dystonia.

Genetic counseling: DYT1 dystonia is inherited in an autosomal dominant manner with 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 testing for DYT1 dystonia are possible.