A.J. van der Kooi, M.D., Ph.D
M. de Visser, M.D., Ph.D.
E.M. Hoogerwaard, M.D., Ph.D.
There is a wide range in age of onset (2-35 year), but in most cases the first symptoms were noticed between the 6th and 18th year of life with a mean age of onset of 11,1 years. Although the time of clinical onset is admittedly an unreliable parameter most studies have found a similar mean age at onset. BMD can also present with delayed walking which is related to an earlier age of onset. Usually patients present with symptoms, including frequent falling, difficulty climbing stairs, waddling gait, poor running, which can be ascribed to weakness of the muscles of the lower Read more
There are two diseases which may mimic BMD: limb girdle muscular dystrophy and spinal muscular atrophy, type III. Since about a decade rapid molecular genetic developments have expanded the field of limb girdle muscular dystrophies (LGMD) which is the most important disease BMD has to differentiated from. The clinical picture of BMD and of autosomal recessive LGMD can be almost identical. Even cardiac involvement may occur in LGMD, albeit in only a small proportion of patients. Ancillary studies including estimation of CK, EMG and histological examination of a muscle biopsy specimen are not helpful in distinguishing one disease from the other. Immunohistochemical analysis of the dystrophin-related proteins, the sarcoglycans, and immunobiochemical analysis of calpain-3 and dysferlin, followed by subsequent identification of the disease-causing mutation, is then the appropriate means to properly establish the diagnosis.
Dystrophin gene deletions account for approximately 65% of Becker patients. Deletions are clustered in two ‘hot spots’, one proximal in the 5’ end (exons 2-20) and one more distal 3’, comprising exons 45-53. BMD is mostly associated with rearrangements (deletions, point mutations, and rarely duplications) in which the translational reading frame is maintained. However, rarely out-of-frame deletions were reported in BMD patients. The reading frame rule holds in about 92% of the cases. Dystrophin, the large protein product of the gene that is localised in the surface membrane, was found to be reduced in quantity or with a different molecular weight in muscle of patients with BMD on Read more