Dystonia Musculorum Deformans 1; Early Onset Primary Dystonia; Early Onset Torsion Dystonia

Early Onset Primary Dystonia (DYT1) typically presents in childhood or adolescence.  The most common presentation is with dystonic muscle contractions causing posturing of a foot, leg, or arm.  The disorder is usually first apparent with movement of specific body parts for specific actions (e.g., writing or walking); however, over time the contractions frequently manifest with more generalized movements and spread to other body regions.  Disease severity varies considerably even within the same family; writer’s cramp may be the only sign in some affected individuals.

DYT1 is an autosomal dominant disorder caused by a three base-pair deletion, c.907_909delGAG, in the TOR1A gene.  No other mutation has been unequivocally identified.  Penetrance is approximately 30%.

1. Confirmation of diagnosis
   1. In individuals with clinical features suggestive of early-onset primary dystonia.
2. Carrier testing:
   1. Although this is an autosomal dominant condition, because of the reduced penetrance, carrier testing may be relevant to identify non-penetrant mutation carriers.  Please refer to limitations section for further information.
3. Prenatal testing (technically feasible but not routinely performed – contact MGL to discuss):
   1. Pregnancies of couples in which one person has DYT1

PCR amplification across the region of the TOR1A gene containing the c.907_909delGAG mutation is performed to determine whether a deletion is present.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.