Presentation: Adult patient with suspected Becker muscular dystrophy

A young man attends the neurology clinic with proximal muscle weakness and leg cramps. He has noticed that his urine sometimes turns brown after he exercises. He has very large calves. Blood tests demonstrate elevated creatinine kinase (CK) levels.

• Genomic testing should be considered in all individuals who present with clinical features of Becker muscular dystrophy, including elevated CK. Progressive symmetrical proximal muscle weakness and/or cardiomyopathy may be present, but are not essential for diagnosis.
• Testing should also be considered in all females who may be manifesting carriers – that is, they present with clinical features such as mild proximal weakness, raised CK and/or cardiomyopathy.
• Female family members of an affected male in whom a diagnosis of Duchenne or Becker muscular dystrophy is suspected on clinical grounds, but in whom genetic confirmation is not available, are also eligible for testing.
• Unaffected individuals may present with a family history of an adult-onset genetic condition. Where signs and/or symptoms suggestive of that condition are not present in the patient (particularly if the patient is male), they should be offered referral to a local clinical genetics service to discuss testing as part of a predictive (presymptomatic) testing pathway.
• A genetic diagnosis may have implications for other family members, and can be particularly relevant during a pregnancy. For some genetic conditions, rapid testing is available for the purposes of pregnancy management. Assessment of symptoms during pregnancy and discussion of the patient’s choices regarding prenatal testing may be offered. If the patient or a close relative is pregnant, you may wish to offer them a referral to the local clinical genetics service for further discussion.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the tests best suits the needs of your patient and/or their family. For Duchenne or Becker muscular dystrophy there are a number of available tests, which are listed below.
  • R73 Duchenne or Becker muscular dystrophy: This panel should be requested if Becker muscular dystrophy is likely to be the diagnosis. It includes single gene sequencing and multiplex ligation-dependent probe amplification (MLPA).
  • R79 Congenital muscular dystrophy: This panel should be considered in cases in which R73 testing is negative and, on clinical examination, muscle biopsy and/or brain MRI, where the patient’s features indicate congenital muscular dystrophy. Discussion with a neuromuscular specialist is recommended. This testing includes whole exome sequencing or a gene panel.
  • R381 Other rare neuromuscular disorders: This panel should be used in cases in which clinical features are atypical and a broader range of conditions are under consideration. It uses whole genome sequencing (WGS), though only genes known to cause rare neuromuscular conditions are analysed.

• For tests that do not include WGS, including R73, you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
• For tests that are undertaken using WGS, including R381, you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number(s) (see How to complete a test order form for WGS for support);
  • complete an NHS GMS record of discussion (RoD) form for each person being tested – for example, if you are undertaking trio testing of an affected patient and their parents, you will need three RoD forms (see How to complete a RoD form for support); and
  • obtain a consultee form signed by an appropriate relative or advocate if the patient does not have capacity to consent to genomic testing.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• GeneReviews: Dystrophinopathies
• NHS England: National Genomic Test Directory
• OMIM: 300376 Muscular dystrophy, Becker type

References:

• American Academy of Pediatrics Section on Cardiology and Cardiac Surgery. ‘Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy’. Pediatrics 2005: volume 116, issue 6, pages 1,569–1,573. DOI: 10.1542/peds.2005-2448

For patients

• Muscular Dystrophy UK: Becker muscular dystrophy
• NHS Inform: Becker muscular dystrophy