Oculopharyngeal muscular dystrophy (OPMD) typically manifests after age 45 with ptosis and dysphagia.  Weakness often spreads to the tongue, facial muscles, and proximal extremities.  More severe cases (5% – 10%) have earlier onset and more pronounced involvement of the extremities.  There is usually a history of the disorder in one or more family members.

OPMD is caused by an expansion of the GCN trinucleotide repeat in exon 1 of the PABPN1 gene.  Normal repeat length is 10.  Expansions of 12 or more repeats are by themselves sufficient to cause disease and, therefore, account for the autosomal dominant inheritance observed in most families.  Autosomal recessive inheritance is observed in transmission of 11-repeat alleles (i.e. homozygotes are affected and heterozygotes are not).

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of OPMD.
2. Carrier testing:
   1. Individuals at risk to be carriers of the autosomal recessive allele (GCN)11 because of a family history of an individual confirmed to have autosomal recessive OMPD or to be a compound heterozygote for (GCN)12-17/(GCN)11.
3. Prenatal testing (technically feasible but not routinely performed – contact MGL to discuss):
   1. Pregnancies of couples at risk of having a child with OPMD due to known mutation(s).
4. Presymptomatic testing:
   1. Adults known to be at risk of developing OPMD because of a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the GCN repeat in the PABPN1 gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.

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. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

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. 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 some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

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 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.