Risk assessment for Duchenne/Becker muscular dystrophy

This section includes information on how the origin of the dystrophin mutation in the family affects risk for another occurrence of Duchenne or Becker muscular dystrophies, and reviews risk assessment for different family presentations.

Risk Assessment Quick Facts

  • The risk for an affected son depends on the cause of the mutation.
  • The risk is highest for sons of carrier mothers:
    • 50% risk for each son to be affected
    • 50% risk for each daughter to be a carrier
    • if the sex of the fetus is unknown, there is a 25% risk for an affected male
  • Risk is reduced, but greater than population risk, for sons of mothers with germline mosaicism
  • For mothers who have a son with Duchenne/Becker caused by a new mutation, risk to other children is not increased

Risk depends on mutation origin

Risk assessment and determination of appropriate carrier testing in dystrophinopathies is complicated by the fact that the mutation can be passed through the family (often indicated by more than one affected male in the family), or can occur de novo. De novo (or new) mutations may occur in the mother, causing her to be the first carrier in the family, or in the affected son. De novo mutations may be found in all cells, or may be mosaic (only in a proportion of cells). Germline mosaicism (mutations present only in a proportion of a mother’s egg cells) are found in perhaps as many as 15% of mothers who are negative on carrier testing. Germline mosaicism is of specific concern, because results from DNA testing on blood would be normal, but risk for further affected boys is still present. Because it is practically impossible to rule out germline mosaicism, mothers with negative results on carrier testing should be cautioned about this possibility.

The image shows how mosaicism occurs. After the fertilized egg begins to divide into specialized cells, a mutation occurs that is passed to subsequent cells (indicated by the asterisk in the image). In germline mosaicism, shown below, the mutation is present in some proportion of the germline cells (e.g. egg cells).

risk.png

Adapted from http://www.genetics.com.au/factsheet/fs13-2.gif

Note: The majority of carrier females are asymptomatic (80-90%), though carriers can present with musculoskeletal and cardiac symptoms (e.g. muscle weakness, fatigue, cardiomyopathy).