Do I need to screen family members if a patient is a carrier of the Becker muscular dystrophy (BMD) gene?

From the Guidelines

Yes, screening family members is recommended when a patient is a carrier of the Becker muscular dystrophy (BMD) gene. Since BMD is an X-linked recessive disorder caused by mutations in the dystrophin gene, female carriers have a 50% chance of passing the mutation to each of their children, with sons who inherit the mutation developing the disease and daughters becoming carriers. Male patients with BMD will pass the mutation to all their daughters but none of their sons. Screening typically involves genetic testing through blood samples to detect the specific dystrophin gene mutation.

Key Points to Consider

• Family members who should be prioritized for screening include the patient's siblings (especially brothers who may be affected), mother (who may be a carrier), maternal aunts and their children, and the patient's own children.
• Early identification of carriers and affected individuals allows for appropriate medical monitoring, timely interventions for those with the disease, and informed reproductive decision-making.
• Genetic counseling should accompany screening to help family members understand inheritance patterns, test results, and available options, as highlighted in the study by 1.
• The importance of genetic testing in the diagnosis of neuromuscular diseases, including BMD, is noted in the study by 1, which emphasizes the need for a precise genetic diagnosis to determine clinical expectations, genetic counseling, and prenatal diagnosis.
• Additionally, the study by 1 recommends testing should be offered to an affected family member first, and in the event of a positive genetic test, cascade screening of the specific mutations can be performed in other family members to identify those at risk.

Recommendations for Screening

• Cascade genetic testing of at-risk family members is recommended for pathogenic and likely pathogenic variants, as stated in the study by 1.
• Genetic testing should ideally be initiated on the person in a family with the most definitive diagnosis and most severe manifestations, as recommended in the study by 1.
• The study by 1 also highlights the importance of genetic testing in determining the timing and modes of cardiovascular assessment and follow-up, and its potential to allow for NMD-specific therapies and mutation-specific therapies in the future.

From the Research

Screening Family Members for Becker Muscular Dystrophy

If a patient is a carrier of the Becker muscular dystrophy (BMD) gene, screening family members is an important consideration. The following points highlight the relevance and methods of screening:

• Genetic Analysis and Counseling: A systematic approach for genetic analysis and genetic counseling of DMD and BMD families, including prenatal and preimplantation diagnosis, is proposed 2.
• Detection of Carriers: Carrier detection is possible by assessing the intensity of relevant bands, but preferably by a non-quantitative test method 2. Multiple ligation-dependent probe amplification (MLPA) is a useful quantitative method for detecting mutations in asymptomatic or symptomatic carriers as well as DMD/BMD patients 3, 4.
• Importance of Screening: Screening family members, particularly female relatives, is crucial as they may be carriers of the disease 3, 4, 5. About one third of potential carriers have not been tested, highlighting the need for further studies to investigate the reasons behind this 5.
• Methods for Screening: Various methods are available for screening, including multiplex polymerase chain reaction, MLPA, and direct DNA sequencing 3, 4. Southern-blot analysis with cDNA probes can also be used to detect female carriers by comparing the intensity of signals corresponding to different exons 4.
• Clinical Consequences: Being a carrier can have far-reaching clinical consequences, including the risk of having offspring with the disease and the risk of cardiomyopathy, for which regular cardiac surveillance is recommended 5.

Key Considerations

• The decision to screen family members should be based on a thorough understanding of the genetic and clinical aspects of BMD.
• Genetic counseling and testing can provide valuable information for family members, enabling them to make informed decisions about their health and reproductive options.
• The choice of screening method depends on various factors, including the specific mutation, family history, and individual preferences.