Duchenne/Becker Muscular Dystrophy


BACKGROUND:

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder occurring in 1:3000 male births. It is characterized initially by proximal muscle weakness usually before age five years. Affected individuals show hypertrophy of the calf muscles, toe walking, waddling gait and the Gower sign (climbing up the legs when rising from a seated position on the floor). Dramatic progression of weakness leads to loss of ambulation by the early teens and death by age 30 from cardiac or respiratory failure. Becker muscular dystrophy (BMD) is an allelic form of this disease with a similar presentation but a much milder clinical course. Age of onset is variable. Symptoms may appear in the teens to early twenties and patients are often ambulatory into their thirties.

DMD and BMD are caused by mutations in the dystrophin gene. 60%-65% of patients have large easily detectible deletions within the gene, approximately 5% have intragenic duplications, and the rest have undetectable small deletions or point mutations. Approximately 1/3 of sporadic cases of DMD/BMD are due to new mutations in the affected individual, and no evidence of the mutation is found in the mother's somatic tissues. However, in 15% of these sporadic cases, the mother's germ cells carry the son's mutation (i.e. she is a germ line mosaic) and further offspring are at high risk for inheriting a dystrophin mutation.

INDICATIONS FOR TESTING:

  • Confirmation of a clinical diagnosis of DMD/BMD.

  • Carrier testing in those with a family history of DMD/BMD.

  • Prenatal testing for at risk pregnancies.

SAMPLE REQUIREMENTS:

Blood: Two 5 ml purple top (EDTA) vacutainers of whole blood inverted several times to mix. Forward within 48 hours at room temperature.

Amniotic fluid: 10-15 ml amniotic fluid from 14th-17th week of gestation or one confluent flask of cultured cells. Send specimen refrigerated, but not frozen (do not ship on dry ice). Please use an overnight courier service.

INTERPRETATION:

Multiplex PCR assays are used to detect 99% of intragenic deletions that account for 60-65% of all dystrophin mutations. Report will include characterization of deletions (when detected), background information and carrier risk assessment by linkage analysis when utilized.

COUNSELING ISSUES:

  1. The absence of a dystrophin deletion does not exclude a diagnosis of DMD/BMD since 35%-40% of mutations are undetectible in these assays.

  2. In families with two or more affected males (the mother of the proband is an obligate carrier) in which no deletion is found, linkage analysis is nearly always informative in determining carrier status of the proband's sisters if an affected or normal brother is available.

  3. In families with only one affected male (the mother of the proband is a carrier in 2/3 cases and not a carrier in 1/3 cases), linkage results may be less informative.

  4. Tests will not detect maternal germ line mosaicism which occurs in approximately 15% of mothers of sporadic DMD/BMD cases.

 

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