Dystrophia Myotonica 1; Steinert’s Disease

Myotonic dystrophy type 1 (DM1) is a disorder of smooth and skeletal muscle that also affects the eye, heart, endocrine system, and central nervous system. The clinical continuum has been divided into roughly three categories: mild (cataract and myotonia), classic (muscle weakness and wasting, myotonia, cataract and, often, cardiac conduction abnormalities), and congenital (severe hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and, frequently, intellectual disability).

DM1 is caused by an increased number of CTG trinucleotide repeats in the 3′ untranslated region of the DMPK gene. The inheritance pattern is autosomal dominant with anticipation. Anticipation is the phenomenon of increased severity or decreased age of onset in successive generation due to expansion of the unstable repeat. In DM1, anticipation is typically greater with maternal transmission of the expanded allele.

DMPK alleles are classified as:

• Normal: 5 to 34 CTG repeats
• Mutable Normal: 35 to 49 repeats
  These alleles are not disease-causing, but may be at risk of expansion into the pathogenic range in subsequent generations.
• Full Penetrance: >50 repeats

In general, longer CTG repeat expansions correlate with an earlier age of onset and more severe disease; however, there is overlap in the repeat ranges associated with the categories of clinical presentation. Individuals with mild DM1 typically have between 50 and ~150 repeats; those with classic DM1 typically have between ~100 to ~1000; and, those with congenital DM1 typically have >1000 repeats. Most often, a child with congenital DM1 has inherited the expanded DMPK allele from the mother. Although expansion into the disease-causing range typically occurs in maternal transmission, paternal inheritance has been described.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of myotonic dystrophy.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies at risk of myotonic dystrophy type 1 because of a history of molecularly confirmed DM1 in one parent.
3. Presymptomatic testing:
   1. Adults known to be at risk of myotonic dystrophy type 1 because of a molecularly confirmed family history of the condition.

PCR and triplet-primed (tp) PCR amplification is performed across the CTG repeat region of the DMPK gene to assess for expansion.  Sizing is performed up to ~100 repeats; sizing beyond 100 repeats is not possible with this assay.    

In rare cases, a repeat collection and testing by Southern blot analysis will be recommended.

For more information, see FAQ

Pregnancy-related/Prenatal

If pregnancy management will be altered, 3 weeks; otherwise, routine TAT.

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).  

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 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. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

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.

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.