Duchenne Muscular Dystrophy Factsheet

For an affected individual

Clinical features
Duchenne Muscular Dystrophy (DMD) is a dystrophinopathy that affects 1 in 3,500 males. Individuals with DMD typically present in early childhood with symptoms including delayed milestones, muscle weakness, progressive difficulty with walking, and cardiomyopathy in adolescence. Most children with DMD lose the ability to walk by 12 years. Cardiomyopathy is present in all individuals with DMD by age 18 years. Most individuals with DMD do not live beyond their twenties.

Diagnosis
Diagnosis of DMD is made through detection of a DMD deletion or mutation. It can be diagnosed from dystrophin analysis from a muscle biopsy. Clinical findings of progressive muscle weakness with onset prior to 5 years and wheelchair dependency prior to 13 years, calf hypertrophy, and elevated serum CK. Some individuals have an X-linked pattern of inheritance are suggestive of a clinical diagnosis of DMD.

Genetics & Inheritance

The DMD gene is on the X chromosome, and the condition is inherited in an X-linked pattern. Approximately 60-70% of individuals with DMD have a deletion of one or more exon of the DMD gene. Other genetic mechanisms for DMD include duplications and point mutations. A new case of DMD in a family without any family history of the condition can be due to an inherited or de novo mutation. In all genetic conditions, there is a risk of de novo mutations, which occur during the development of egg or sperm cells in the parents of the affected individual. In some conditions, such as DMD, de novo mutations are relatively common. In a new case of DMD, there is a 1 in 3 (33%) chance the patient has a de novo mutation. Certain mutations in the DMD gene can also cause the more mild condition of Becker Muscular Dystrophy and DMD-associated Dilated Cardiomyopathy (DCM).

Clinical testing
Genetics testing can detect most cases of DMD: Deletion/duplication analysis through multiplex ligation probe amplification (MLPA) or chromosome microarray can diagnosis up to 55-75% of cases. Sequence analysis will detect an additional 20-35% of cases.

Management
There is no cure for DMD, but there have been recent promising advances made in treatment options. Children with DMD are often managed through multidisciplinary clinics due to the systemic impact of the disease. Treatments are available to manage the symptoms and in some cases, slow disease progression. Cardiomyopathy may be managed by treatment with ACE inhibitors and/or beta blockers and heart transplantation. Corticosteroid therapy may slow progression of muscle weakness. Physical therapy and assistive devices can help improve function and quality of life.

Published October 2013 NCHPEG All rights reserved

For a carrier female

Clinical features
Up to 24% of DMD carrier females can have symptoms of mild to moderate muscle weakness, myalgia, left ventricle dilation, and dilated cardiomyopathy. It is unlikely for a DMD carrier female to present with signs of classic DMD; affected females are almost always more mildly affected than males. Additionally, female carriers are at increased risk to develop neuromuscular disease. For more information about the risks to women with DMD mutations, see Hoogerwaard, et. al, 1999 and van Westrum et. al, 2011.

Genetic Counseling
Carrier risk for the mother of a child with DMD (with a negative family history) There is a 2 in 3 (66%) chance the mother is a DMD carrier. She could be a full carrier, which means all the cells of her body have the DMD mutation. She could have mosaicism for the DMD mutation. In this case, some of her cells will have the DMD mutation and some will not. Germline mosaicism is where the mutation is present in some of her egg cells only.

There is a 1 in 3 (33%) chance the mutation was a de novo, or spontaneous event, and the mother is NOT a carrier. Counseling It is important to talk with the family about not only the patients prognosis and management, but also the risk to his siblings and other family members. There is a chance that women in the family are carriers and could pass DMD onto a boy. Recurrence risks based on carrier status A woman who tests positive as a carrier of DMD mutations But does not know the sex of the child has a o 25% chance to have a male child with DMD o 25% chance to have a female child who is a carrier for DMD o 50% chance to have a child who is neither affected nor a carrier And knows she is going to have a male: o The boy has a 50% chance to have DMD And knows she is going to have a female: o The girl has a 50% chance to be a DMD carrier

A woman who tests negative as a carrier of DMD mutations Is most likely not a carrier and will not have another child with DMD. There is a small chance the family carries an undetectable DMD mutation. There is also a chance of germline mosaicism. The chance she would have germline mosaicism (15 20%) and go on to have a child with DMD (25%) is 4 5% for each pregnancy.

References
GeneReviews: Dystrophinopathies at www.ncbi.nlm.nih.gov/books/NBK1119/ Bushby K, Finkel R, Bimkrant D et al for the DMD Care Considerations Working Group. 2010. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 9;177-89. Hoogerwaard EM, van der Wouw PA, Wilde AA et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1999b;9:34751.

Published October 2013 NCHPEG All rights reserved

Schade van Westrum SM, Hoogerwaard EM, Dekker L et al. Cardiac Abnormalities in a follow-up study on carriers of Duchenne and Becker Muscular Dystrophy. Neurology. 2011. 77(1):62-6.

Published October 2013 NCHPEG All rights reserved