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Conditions/Tests

Myotonic Dystrophy Type 2

Myotonic Dystrophy Type 2

Proximal Myotonic Myopathy (PROMM); Ricker Syndrome; DM2

It is the responsibility of the ordering physician to ensure that informed consent has been obtained from the patient/legal guardian before ordering genetic testing. Please review the following Pre-Test Counselling Information with your patient before requesting any of our genetic tests.

Clinical Features

Myotonic Dystrophy Type 2 (DM2) is characterized by myotonia and muscle dysfunction (weakness, pain and stiffness), and may include other multi-system involvement including cataracts and type 2 diabetes.  Onset of symptoms usually occurs between the second to seventh decade, most typically in the third or fourth decade. See PMID: 20301639 for an overview.

Genetics

DM2 is an autosomal dominant disorder caused by expansion of a CCTG repeat in intron 1 of the CNBP gene.  The CCTG repeat is part of a complex repeat motif consisting of (TG)n(TCTG)n(CCTG)n.

CNBP alleles are typically classified based on total size of the repeat motif, which roughly translates to:

  • Normal alleles: up to ~54 CCTG repeats, including mutable normal alleles (27 – ~54 CCTG repeats)
  • Full Penetrance: ~55 to over 11,000 CCTG repeats, with a mean of 5000 repeats.

There is no known correlation between the size of the expansion and the severity of the symptoms.

CCTG repeat alleles in the mutable normal range are rare and, as such, their clinical significance is not well characterized.

Indications for Testing

  1. Confirmation of diagnosis:
    1. In individuals with clinical features suggestive of myotonic dystrophy.
  2. Presymptomatic testing:
    1. In adults known to be at risk of myotonic dystrophy type 2 because of a molecularly confirmed family history of the condition.

Description of this Assay

Standard PCR amplification is performed across the (TG)n(TCTG)n(CCTG)n repeat tract of the CNBP gene.  Repeat-primed PCR amplification is performed to assess for the presence of expanded allele(s) not amplifiable by standard PCR.  Repeat size, beyond normal or expanded, is not reported.

Sensitivity and Limitations

The categorization of expanded CNBP CCTG repeat alleles is complicated by the presence of somatic mosaicism (varying lengths of allele due to somatic instability of the CCTG expansion).  Almost 100% of individuals with DM2 will have a CCTG repeat expansion in the CNBP gene. The sensitivity of detection for the CNBP CCTG repeat expansion approaches 100%; however, PCR based techniques do not generally allow for accurate sizing of the CCTG repeat expansion.  

Turnaround Time

Routine

4 weeks

Specimen Requirements

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).  

Shipping Address

Specimen Receiving Room 2J20

Children’s & Women’s Health Centre of British Columbia – Laboratory

4500 Oak Street, Vancouver, BC, V6H 3N1


Test Price and Billing

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.

Cautions

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member.  Ideally, this information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In certain scenarios of repeat size mosaicism, false negative results may occur.  If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative 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.