Presentation: Patient with a family history of Duchenne or Becker muscular dystrophy

A young woman and her husband visit your surgery for advice. They would like to start a family but are concerned because the woman’s older brother had DMD, dying at 22 years old. Following her brother’s diagnosis, testing revealed that her mother was a carrier. Your patient was not tested at the time.

• DMD and BMD are X-linked recessive conditions.
• Both cause progressive muscular weakness, but DMD is more severe, with an earlier onset of symptoms and a more rapid progression.
• Females are usually unaffected but rarely may be a ‘manifesting carrier’, developing cardiac and/or skeletal muscle weakness.
• Individuals with a family history of DMD or BMD may be at risk of being affected (if male) or being a carrier (if female).
  • Affected males cannot pass the condition on to their sons, but all their daughters will be carriers.
  • Female carriers have a 50% (1-in-2) chance of passing on the condition to their sons, and their daughters have a 50% (1-in-2) chance of being carriers.
• About one-third of cases of DMD, and half of cases of BMD, occur de novo (meaning arising in the individual for the first time and not inherited from a parent).
  • If a mother with a child affected with DMD or BMD is found not to be a carrier, there is still a small chance of affected future pregnancies, due to a risk of germline mosaicism.
• Flags to an underlying genetic diagnosis in boys include:
  • known family history of the condition;
  • family history of development of weakness and wasting, particularly of proximal muscles, in early childhood;
  • delayed motor milestones;
  • waddling gait; and
  • Gower’s sign – using hands and/or arms to ‘walk up’ their own body to rise from a sitting or squatting position – may be evident.

• Counsel the couple that if they were to find themselves pregnant, they would need to seek an urgent referral (as per local pathways) for counselling regarding reproductive options, including non-invasive prenatal diagnosis in the first trimester.
• Take a thorough history from your patient. Be alert for any clues that a female patient may be a mildly manifesting carrier.
• Take a brief family history to establish the relationship to the affected family member and confirm that your patient is indeed at risk.
• Explain the basic inheritance of DMD/BMD.
  • If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Refer to your regional clinical genetics service for counselling and testing, including the affected relative and/or carrier’s name and date of birth.
• Refer female carriers for cardiac monitoring under cardiology services, which may include an electrocardiogram (ECG), cardiac magnetic resonance imaging (cMRI) and an echocardiogram (echo).
• New gene-directed therapies and trials for DMD may be available for certain eligible patients. For more details of these, see this Knowledge Hub resource: Duchenne Muscular Dystrophy.
• Reproductive options are available for carriers, including prenatal testing and preimplantation genetic testing.
  • For more information, see Presentation: Pregnancy at risk of Duchenne or Becker muscular dystrophy.

For clinicians

• National Genomic Test Directory
• National Organization for Rare Disorders: Duchenne Muscular Dystrophy
• TREAT-NMD: Care Guides Duchenne Muscular Dystrophy

For patients

• Duchenne UK
• TREAT-NMD: Care Guides Duchenne Muscular Dystrophy (guide for families)
• Muscular Dystrophy UK: Becker muscular dystrophy