Gene: Dystrophin (DMD) on Xp21.2
DMD and BMD are neuromuscular diseases characterized by progressive muscle wasting and weakness due to degeneration of skeletal, smooth and cardiac muscle. DMD is more frequent, occurs earlier and is more severe than BMD. DMD and BMD primarily affect males.
In DMD, walking is often delayed. Cognitive functions can be altered. Diagnosis is generally made at the age of 5 when children present with a waddling gait and talipes equines with calf hypertrophy (positive Gower's sign). Inability to walk appears by 10 to 12 years of age. Scoliosis, cardiomyopathy and restrictive respiratory failure progressively appear.
BMD appears later, between the ages of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Other clinical forms also exist (isolated cardiomyopathy, exercise intolerance, and symptomatic forms of muscular dystrophy of Duchenne and Becker in female carriers; see this term).
Both X-linked recessive diseases are caused by dystrophin deficiency in skeletal and heart muscles, leading to progressive necrotizing lesions. The dystrophin gene (DMD) is located at Xp21.2 and encodes several isoforms.
The clinical diagnosis can be confirmed by several methods. Creatine phosphokinase levels are 50- to 200-fold (DMD) or 10- to 35-fold (BMD) higher than standard values. Muscular biopsy shows dystrophic features (necrotic and regenerative fibers). Immunohistochemical studies show a total absence of dystrophin (DMD) or altered quantity and/or quality (BMD).
Molecular analysis most frequently shows deletions of the exon(s) of DMD gene in 65% of cases. 5% of cases are caused by the duplication of the gene/exons. 30% of cases associated with the point mutations in the DMD gene.
Genetic counselling of DMD/BMD patients and their families is offered at CMG.
Prenatal diagnosis requires the most precise molecular diagnosis possible in the index case and is performed at CMG if deletion is detected and confirmed.
Treatment is symptomatic and multidisciplinary: orthopedic (prevention and treatment of retractions, physiotherapy, fitting with prosthesis, spinal arthrodesis (at 12-15 years of age), and technical support), respiratory (prevention and treatment of infections, respiratory physiotherapy, and ventilation), and cardiac (ACE inhibitors and heart protection). Corticotherapy helps to stabilize motor abilities. School and social integration is essential (role of patient associations). Progression is severe with end-stage cardiorespiratory failure in the young adult with DMD; it is slower and life span is subnormal to normal for BMD.
Detection: We offer DNA test for the detection of the 26 most frequent DMD exons’ deletions using the multiplex PCR technique.
Specimen Requirements: genomic DNA is isolated from the peripheral blood, collected in 2 ml EDTA Vacutainer tube (lavender top). In case if DNA is already extracted, the minimum concentration should be 50ng/µl.
Transportation: The blood specimen can be stored in the refrigerator (for 1 or 2 days) and shipped to CMG at room temperature. In case of the DNA, it can be shipped to CMG at room temperature within 1-2 days.
Turnaround time: 10-15 days
For further information please contact:
Tel.: (+374 10) 544367
Fax: (+374 10) 544366