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DUCHENNE DYSTROPHY

Background
Medical Management Considerations
References
Resources for Families
Advisory Committee
Publication Information

Learning Points

  • Restate the occurrence of Duchenne Dystrophy (1in 3,500) and the fact that there is a 50% recurrence risk for male offspring of carrier mothers.
  • Identify diagnostic tests for Duchenne Dystrophy [blood test (creatine kinase level), DNA analysis in perinatal leukocytes, muscle biopsy].
  • Recognize six clinical features of Duchenne Dystrophy; e.g.,
    • Extreme deficiency of dystrophin
    • Elevated levels of serum creatine kinase and other enzymes (diminish over time)
    • Hypotonia
    • Progressive muscle weakness and atrophy (esp. proximal body muscles)
    • Developmental delay, often delay in walking
    • Waddling gait and difficulty climbing stairs, etc.
  • Delineate five medical management considerations for Duchenne Dystrophy; e.g.,
    • Assess lung function annually
    • Consider noninvasive intermittent positive ventilation as needed
    • Assess cardiac function annually
    • Monitor for muscle weakness and atrophy
    • Recommend daily stretching exercises, etc.
  • Refer families to appropriate resources on Duchenne Dystrophy.

BACKGROUND
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Description and Cause

Duchenne Dystrophy, the most severe form of muscular dystrophy, is an inherited neuromuscular disorder with physical and often intellectual implications. It is the most common lethal genetic disorder. Duchenne Dystrophy is caused by a mutation in the dystrophin gene located on the short arm of the X chromosome. The result is absent or very low content of dystrophin, the protein that normally provides the structure for cell membranes to adhere to cell material, thus keeping cells intact. Muscle cells eventually die without enough dystrophin, and those cells are replaced by fibrosis (scar) tissue. About 1/3 of cases are new mutations, while 2/3 are inherited.

Occurrence

  • 1:3,500 births (males only, with rare exceptions)
  • There is a 50% recurrence risk for male offspring of carrier mothers.

Diagnosis

  1. Blood test: creatine kinase levels 50-100 times higher than normal for unaffected individuals
  2. DNA analysis in perinatal leukocytes
  3. Muscle biopsy: dystrophin content <3% normal

Clinical features

  • Extreme deficiency of dystrophin
  • Elevated levels of serum creatine kinase and other enzymes (diminish over time)
  • Hypotonia
  • Progressive muscle weakness and atrophy (esp. proximal body muscles)
  • Developmental delay, often delay in walking
  • Waddling gait and difficulty climbing stairs
  • Diminished or absent patellar tendon reflexes
  • Gower sign by age 5 to 8
  • Hypertrophy of muscles, principally of calf
  • Tight heel cords associated with contractures (beginning with ankles)
  • Leg pain
  • Contractures (beginning with ankles, hips and knees, then upper limbs)
  • Loss of ambulation between age 9 and 14
  • Deteriorating lung function
  • Early death (median age 17; maximum 30s)

Common Associations

  • Scoliosis (75-90% if wheelchair bound)
  • Kyphosis
  • Respiratory failure
  • Pneumonia
  • Cardiomyopathy
  • Chronic cardiac failure (up to 15%)
  • Mental retardation (25-30%), usually mild
  • Gastrointestinal disorders (dysphagia, acute gastric dilation, megacolon, volvulus, cramping pain, malabsorption)
  • Malignant hyperthermia or hypothermia
  • Obesity

MEDICAL MANAGEMENT CONSIDERATIONS
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Note: These considerations are in addition to the normal medical care provided to an individual without Duchenne Dystrophy. Although many recommendations can be addressed through clinical examination by the primary care provider, a multidisciplinary team approach (primary care physician, neurologist, pulmonologist, physical therapist, occupational therapist, nurse, orthopedist, social worker) is the standard of care for persons with Duchenne Dystrophy. Multidisciplinary care may be obtained through programs such as California Children Services (CCS) or clinics funded by the Muscular Dystrophy Association.

Treatment of Duchenne Dystrophy is primarily focused on managing the symptoms in an effort to maximize the quality of life and delay the progression of the disease. In the past few years, new therapies have become plausible as a result of the cloning of the Duchenne gene in 1996. Although genetic therapies provide much hope for successful treatment, they are still being researched and tested.

The function of the lungs, which depends mostly on the strength of the diaphragm muscle, usually determines the length of life for affected individuals.

Upon Diagnosis

Once diagnosis is confirmed (see “Diagnosis” above):

  • Assess muscle function
  • Assess lung function
  • Provide genetic counseling, including discussion of recurrence risk (or refer to genetic counselor who is knowledgeable regarding Duchenne Dystrophy)
  • Refer to early intervention programs (if diagnosed before age 3) and Duchenne Dystrophy and/or disability support groups
  • Discuss possibility of SSI enrollment

Ongoing (all ages)

  • Assess lung function annually
  • Consider noninvasive intermittent positive ventilation as needed
  • Assess cardiac function annually
  • Monitor for muscle weakness and atrophy
  • Recommend daily stretching exercises
  • Recommend mild exercise as long as no pain or exhaustion is experienced
  • Refer for physical and occupational therapy evaluation as needed
  • Discuss durable medical equipment options such as ankle supports, leg braces, wheelchairs with appropriate seating, and powered wheelchairs as needed
  • Refer to orthotist or orthopedic surgeon as needed
  • Monitor for scoliosis
  • Refer to nutritionist or registered dietician because of decreased caloric requirements
  • Consider surgery to release contractures or fixation of joints
  • Recommend epidural anesthesia as an alternative to general anesthesia in surgery to prevent cardiorespiratory complications
  • Refer for psychological evaluation and assessment of cognitive function as needed; refer for psychological counseling as needed
  • Encourage children to be independent as much and as long as possible

Possible Interventions

  • Prednisone and where available, Deflazacort, can be used to improve muscle strength and function
  • Surgical correction of contractures; tenotomy of the Achilles tendon; posterior tibial-tendon transfer surgery
  • Gene therapy: (1) adenovirus-mediated dystrophin gene transfer; and (2) upregulation of utrophin, a natural dystrophin analog (still being researched)
  • Myoblast transplantation to replace dystrophin (both still being researched)

REFERENCES
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Peer-reviewed Journal Articles/Academies

Bach, J.R., et al. (1997). Prevention of Pulmonary Morbidity for Patients with Duchenne Muscular Dystrophy. Chest, 112(4), 1024-1028.

Birch, J.G. (1998). Orthopedic management of Neuromuscular Disorders in Children. Seminars in Pediatric Neurology, 5(2), 78-91.

Brook, P.D., et al. (1996). Spinal Fusion in Duchenne’s Muscular Dystrophy. Journal of Pediatric Orthopedics, 16(30), 324-331.

Galasko, C.S., et al. (1995). Lung Function in Duchenne Muscular Dystrophy. European Spine Journal, 4(5), 263-267.

Karpati, G, et al. (1997). Gene Therapy Research for Duchenne and Becker Muscular Dystrophies. Current Opinion in Neurology, 10(5), 430-435.

Mendell, J.R. et al. (1995). Myoblast Transfer in the Treatment of Duchenne’s Muscular Dystrophy. New England Journal of Medicine, 333(13), 832-838.

Moxley, R.T. et al. (2005). Practice Parameter: Corticosteroid Treatment of Duchenne Dystrophy. Neurology, 64, 13-20. Accessed December 9, 2005.

Vignos, P.J.et al. (1996). Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Journal of Bone and Joint Surgery, 78(12), 1844-1852.

Warren, R.H., S.H. Alderson. (1996). A Pulmonary Monitoring and Treatment Plan for Children with Duchenne-Type Muscular Dystrophies. Journal of the Arkansas Medical Society, 93(7), 333-337.

Special Interest Groups/Other Publications

American Academy of Neurology. Corticosteroids for Duchenne muscular dystrophy. AAN guideline summary for parents and caregivers. Accessed December 9, 2005.

Batshaw, M.L., Perret, Y.M. (1992). Children with Disabilities. Baltimore: Paul H. Brookes.

Capute, A.J., Accardo P.J. (1996). Developmental Disabilities in Infancy and Childhood: Vol. 1. Neurodevelopmental Diagnosis and Treatment. Baltimore: Paul H. Brookes Publishing.

Capute, A.J. & Accardo P.J. (1996). Developmental Disabilities in Infancy and Childhood: Vol 2. The Spectrum of Developmental Disabilities. Baltimore: Paul H. Brookes Publishing.

The Parent Project for Duchenne Muscular Dystrophy.

Griesemer, D.A. & Waheed, N. (1999). Muscular Dystrophy. In M.R. Dambro (ed.), Griffith’s 5 Minute Clinical Consult (pp. 704-705). Baltimore: Lippincott Williams & Wilkins.

Guideline summaries for clinicians and parent/caregivers

RESOURCES FOR FAMILIES
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California Department of Developmental Services
916-654-1690

California Regional Centers
915-654-1958

Duchenne Muscular Dystrophy Research Center, University of Pittsburgh
412-648-9024

Duchenne Parent Project
800-714-KIDS

European Alliance of Muscular Dystrophy Associations

Exceptional Parent Magazine
800-EPARENT

March of Dimes Birth Defects Foundation
916-922-1913

ADVISORY COMMITTEE
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Theodore A. Kastner, M.D., M.S.
Felice Weber Parisi, M.D., M.P.H.
Mary Ann Lewis, Dr.P.H., R.N., F.A.A.N.
Joan M. Reese, M.D., M.P.H.
Jaime D. Mejlszenkier, M.D., F.A.A.N.

PUBLICATION INFORMATION
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This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services.