Presentation: Patient with suspected facioscapulohumeral muscular dystrophy (FSHD)

A young woman attends the neurology clinic with mobility problems and reports frequent trips and falls over the past few years. She also reports that her face looks different when compared with old photos. She finds soap in her eyes when she washes her hair, and she can no longer whistle or drink through a straw. She finds reaching for things above her head difficult.

• Genomic testing should be considered if there are clinical features suggestive of facioscapulohumeral muscular dystrophy (FSHD). The typical history and examination findings for FSHD are:
  • slowly progressive muscle weakness in a typical distribution involving the facial and shoulder girdle muscles with scapular winging (often asymmetric);
  • weakness of trunk (protruding abdomen, lumbar lordosis); and
  • weakness of leg muscles (foot drop and hamstring weakness).
• 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, 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 a 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 panels best suits the needs of your patient and/or their family. For patients with symptoms of FSHD, two tests are available. They are known as FSHD1 and FSHD2.
  • R74 Facioscapulohumeral muscular dystrophy (also known as FSHD1): This is the first-line test for suspected FSHD. It tests for the presence of DUX4 short tandem repeats (STRs). Repeat contractions are not yet reliably identified using whole genome sequencing (WGS).
  • R345 Facioscapulohumeral muscular dystrophy – extended testing (also known as FSHD2): This is the extended testing panel for FSHD, used in cases in which first-line testing for DUX4 contraction is negative or borderline and the clinical features are highly suggestive of FSHD1.
• For patients whose phenotype is atypical and/or FSHD1 and FSHD2 tests are negative, other panels can be considered.
  • R381 Other rare neuromuscular disorders: This test uses WGS to look for variants associated with a wide spectrum of neuromuscular disorders. As above, this test does not include FSHD analysis, therefore R74 should be requested where indicated.
• For tests that do not include WGS, including R74 and R345:
  • 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 where available, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support in completing WGS-specific forms); and
  • 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 individual 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 an adult patient does not have capacity to consent to genomic testing.
• When testing in children, parental samples may be helpful for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed. Parental testing may inadvertently reveal an unexpected positive result (this is predictive or presymptomatic 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 was 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: Facioscapulohumeral muscular dystrophy
• Genomics England: NHS GMS Signed Off Panels Resource
• NHS England: National Genomic Test Directory
• OMIM: #158900 Facioscapulohumeral muscular dystrophy 1

References:

• Lassche S, Mul K, Voermans NC and others. ‘What’s in a name? The clinical features of facioscapulohumeral muscular dystrophy’. Practical Neurology 2016: volume 16, issue 3, pages 201–207. DOI: 10.1136/practneurol-2015-001353

For patients

• FSHD Society
• FSH-MD Support Group UK
• UK FSHD Patient Registry