Genetics of Duchenne Muscular Dystrophy

Duchenne, Intermediate, and Becker Muscular Dystrophy (DMD/IMD/BMD) are severe to mild forms of the disease along a clinical spectrum that are caused by alterations in the DMD gene. This gene encodes the dystrophin protein, a membrane-associated contractile protein found in skeletal muscle.

Location and Transmission of the DMD Gene
The DMD gene is found on the X chromosome in the Xp21 region. Therefore, DMD (and IMD/BMD) are transmitted as X-linked disorders. Females have two X chromosomes, and therefore two copies of all the genes on the X chromosome. A single normal X chromosome with a "normal" (not altered or changed) DMD gene is sufficient to prevent the disease from being exhibited in most cases (except in manifesting carriers). Males will exhibit the disease if the X chromosome they receive has a DMD gene alteration. Transmission from mother to son occurs in about 2/3 of cases; in about 1/3 of cases, the mutation arises spontaneously.

Genetic Testing
In approximately 95% of cases, genetic testing for mutations in the DMD gene is successful, obviating muscle biopsy given a clinical picture of DMD (University of Utah DMD Deletion and Mutation Screening). Testing is also available in asymptomatic females 18 and older to determine their status as a carrier of the DMD gene alteration. (This is important for more than genetic reasons; if they are carriers, they are at risk for cardiomyopathy.) However, mothers of affected boys who have negative carrier testing (for the known mutation in their affected son), may carry the mutation in a portion of their egg cells. This is called gonadal or germline mosaicism and means a woman's germ cell line (her egg cells) may have X chromosomes with the mutation, but her somatic cells do not. This phenomenon is estimated to occur in approximately 10-15 % of mothers of affected boys.

Genetic Counseling
Genetic counseling to discuss testing results is important for families to receive as part of the care of a child with DMD/IMD/BMD. Families will then have a better understanding of their recurrence risks for current and future generations in the family. Testing may eventually guide treatment options as well; in fact clinical trials for treatment options that are specific for certain gene alterations are currently underway. Parent Project - DMD Prenatal diagnosis and preimplantation testing is available when the mutation in the DMD gene has been identified in the family.

Females as Manifesting Carriers
Rarely, females with one normal gene and one altered DMD gene may have symptoms of muscle weakness, cramping, high creatine kinase and cardiomyopathy. These females are called "manifesting carriers". These symptoms are thought to be due to nonrandom inactivation of one of the X chromosomes (by the Lyon Hypothesis).

Cardiomyopathy in Carrier Females
Females who have been identified as carriers, even those without any symptoms of systemic muscle weakness, should be screened for cardiomyopathy. CDC - New Comprehensive DMD Care Considerations (PDF Document 505 KB)


Information & Support

For Professionals

Dystrophinopathies (GeneReviews)
Detailed overview of the dystrophinopathies, from GeneReviews; supported by the National Library of Medicine and the National Center for Biotechnology Information.

United Dystrophinopathy Project
Link to the website for enrollment in the United Dystrophinopathy research project (one of the centers for this study is the University of Utah). Boys with DMD, BMD, and intermediate MD receive genetic testing and periodic strength and functioning assessments. Fee-based genetic testing without enrollment in the research project is also available.

Practice Guidelines

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C.
The Diagnosis and Management of Duchenne Muscular Dystrophy, Parts 1 and 2.
The Lancet Neurology ; (2010) Accessed on 2/28/2011.
A major international consensus document setting out best practice in care for Duchenne muscular dystrophy (DMD) published in the Lancet Neurology journal in January and February 2010.

Helpful Articles

Hausmanowa-Petrusewicz I, Fidziańska A, Niebrój-Dobosz I, Dorobek M, Bojakowski J.
Dystrophinopathies in females.
Folia Neuropathol. 2000;38(1):7-12. PubMed abstract


Author: Lynne M Kerr, MD, PhD - 11/2008
Reviewing Author: Karin Dent, MS, CGC - 8/2009