Becker and Duchenne Muscular Dystrophy
Disorders of progress muscle weakness, DMD 🧬gene, X-linked
Overview
Rapidly progressive, symmetric muscle weakness and wasting due to degeneration of skeletal, smooth, and cardiac muscle. The DMD gene is the largest known human gene, containing 79 exons spanning 2.2 Mb.
Testing
Multiplex ligation-dependent probe amplification (MLPA) or exon sequencing on DNA level.
⬆️ Creatine Kinase (increased on serum testing)
Recurrence Risk
1/3 de novo rate
Family w/more than one affected individual, the mother of an affected male is an obligate heterozygote.
If a male is the only affected family member (simplex case), the mother may be a heterozygote or its de novo
Recommendations for the mother of a proband include molecular genetic testing; if heterozygous, need cardiac 🫀 surveillance
Symptoms
Gower sign/maneuver - arrives at a standing by using the hands to “walk up” the body until they are upright
Delayed motor milestones
Elevated creatine phosphokinase (CK) concentration and muscle cramps
Calf hypertrophy - affected muscles are weak even though they appear larger
Scoliosis
Inability to walk by 12 - Wheelchair use
DMD-associated dilated cardiomyopathy (DCM) = 90%
Treatment
ACE inhibitors w/&w/o beta blockers - cardiomyopathy in both DMD and BMD.
Congestive heart failure - diuretics and oxygen as needed
Cardiac transplantation - severe dilated cardiomyopathy and BMD
Corticosteroid therapy improves muscle strength and function
Dystrophin restoration therapies
Additional Information
Average lifespan ≈ about third decade
Carrier females may manifest signs of disease, often with a classic dystrophinopathy
Skewed X inactivation
