SUMMARY:

Reproductive carrier screening is an increasingly common practice used to identify pregnancies that are at risk for genetic disorders. Although most carriers are unaffected, carrier status for some conditions can lead to disease symptoms. The DMD gene is associated with X-linked Duchenne (DMD) and Becker (BMD) type muscular dystrophies, which are a spectrum of neuromuscular disorders characterized by progressive muscle weakness and cardiomyopathy. Testing for DMD is frequently offered as part of a reproductive carrier screening panel, even if there is no family history.  Thus, some DMD carriers are identified unexpectedly. These individuals should be aware of potential disease manifestations and understand the recommended surveillance for cardiac disease

BACKGROUND:

• DMD is included in the ACMG’s “Tier 3” recommendations for carrier screening, which should be offered to all patients who are pregnant or are considering pregnancy (see ‘Related ObG Topics’ below)
  • Patients with a family history of DMD or BMD may require targeted testing, depending on the methods used to detect their familial variant
• Pathogenic variants in the DMD gene are associated with DMD and BMD type muscular dystrophies
  • These disorders primarily affect males
  • DMD and BMD are distinguished by clinical severity | BMD is used to describe less severe cases with later age of onset
• DMD and BMD are X-linked. For the offspring of female carriers:
  • Males have a 50% chance to be affected
  • Females have a 50% chance to be carriers

Note: Unlike most disorders on prenatal carrier testing panels which are autosomal recessive, DMD is X-linked | Therefore, testing the reproductive partner of a female carrier is not required to determine risk to the fetus

Symptoms associated with Female Carriers

• Genetic female (46,XX) DMD carriers are typically asymptomatic, but some experience mild to moderate muscle weakness or cardiac involvement
• DMD carriers may have the following signs/symptoms
  • Mild/moderate muscle weakness: 14% to 19%
  • Myalgia/cramps: 5%
  • Left ventricle dilation: 16% to 19%
  • Dilated cardiomyopathy: up to 8%
  • Elevated serum creatine kinase (CK) concentration: 30% to 50%

KEY POINTS:

Referrals for Multidisciplinary Care During Pregnancy and Beyond

• Cardiology  
  • Complete cardiac evaluation and/or cardiac MRI is recommended for female carriers of DMD to assess for dilated cardiomyopathy (DCM), characterized by left ventricular dilation and congestive heart failure
  • Cardiac surveillance should begin in late adolescence/early adulthood
• Maternal Fetal Medicine
  • Pregnant DMD carriers with cardiac disease should be referred for consultation with a high-risk obstetrician
  • If fetus is male (by ultrasound or NIPS), offer fetal diagnostic testing for DMD via chorionic villus sampling or amniocentesis
• Genetic Services
  • Educate about risk of developing DCM and/or symptoms of heart failure
  • Counsel about risk to offspring and other family members
    • Male offspring: 50% risk to be affected with BMD or DMD (variant dependent)
    • Female relatives may be carriers with risk for DMD symptoms

Learn More – Primary Sources:

AAP: Cardiovascular Health Supervision for Individuals Affected by Duchenne or Becker Muscular Dystrophy

DMD Care Considerations Working Group: Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

Gene Reviews: Dystrophinopathies

Locate a Genetic Counselor or Genetics Services: 

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC 

Genetic Services Locator-CAGC 

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Related ObG Topics:

ACMG Recommendations for Preconception and Prenatal Carrier Screening