A child has recently been diagnosed with Duchenne’s muscular dystrophy. The parents are receiving genetic counseling prior to planning another pregnancy. Which of the following statements includes the most accurate information?
A. Duchenne’s is an X-linked recessive disorder, so daughters have a 50% chance of being carriers and sons a 50% chance of developing the disease.
B. Duchenne’s is an X-linked recessive disorder, so both daughters and sons have a 50% chance of developing the disease.
C. Each child has a 1 in 4 (25%) chance of developing the disorder.
D. Sons only have a 1 in 4 (25%) chance of developing the disorder.
Correct Answer: A. Duchenne’s is an X-linked recessive disorder, so daughters have a 50% chance of being carriers and sons a 50% chance of developing the disease.
The recessive Duchenne gene is located on one of the two X chromosomes of a female carrier. DMD is a genetic disease due to the mutation of the dystrophin gene, located on chromosome Xp21. It is inherited as an X- linked recessive trait; however, approximately 30% of cases are due to new mutations. Carrier females show no evidence of muscular weakness; however, symptomatic female carriers have been described. About 2.5% to 20% of female carriers may be affected. This can be explained by the Lyon hypothesis in which the normal X chromosome becomes inactivated, and the X chromosome with the mutation is expressed.
Option B: If her son receives the X bearing the gene he will be affected. Female carriers can become symptomatic if they are associated with Turner’s syndrome (45X) or mosaic Turner karyotype, balanced X autosome translocations with breakpoints within the dystrophin gene and preferential inactivation of the normal X, and females with a normal karyotype but with nonrandom X chromosome inactivation with diminished expression of the normal dystrophin allele.
Option C: Daughters are not affected, but 50% are carriers because they inherit one copy of the defective gene from the mother. Mutations in the dystrophin gene result in diseases known as dystrophinopathies, which encompass Duchenne muscular dystrophy, Becker muscular dystrophy, and an intermediate form.
Option D: There is a 50% chance of a son being affected. Mutations result in a limited production of the dystrophin protein, which results in loss of the myofiber membrane integrity with repeated cycles of necrosis and regeneration. Fibrous connective tissue and fat progressively replace muscle leading to clinical features.