Authors
A.J. van der Kooi, M.D., Ph.D
M. de Visser, M.D., Ph.D.
E.M. Hoogerwaard, M.D., Ph.D.
Clinical features
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
Natural course and prognosis
The clinical picture is heterogeneous. Patients can be asymptomatic until their mid sixties, whereas the occasional patient shows rapid progression of muscle weakness comparable to that of DMD.
The age of loss of ambulation ranges from 12 to Read more
Epidemiology
The prevalence rate of BMD is approximately 2,5/100 000 in all epidemiological studies.
The cumulative birth incidence of BMD is at least 1 in 18 450 male live births.
Differential diagnosis
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.
Ancillary investigations
Serum creatine kinase (CK) activity is almost invariably elevated. Short-duration, low-amplitude motor unit action potential (MUAPs) are consistent with a myopathy. However, in BMD, it is not unusual to find high frequency discharges, positive sharp waves or fibrillations (Bradley et al. 1978; Kuhn et al. 1979; Sunohara et al. 1990) or long-duration polyphasic MUAPs (Uncini et al. 1990). These findings were found to correlate with the appearance of regenerating muscle fibres. These apparently ‘neurogenic’ findings may give rise to confusion with autosomal recessive proximal spinal muscular atrophy (Kugelberg-Welander Read more
Genetics
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
Therapy
Therapeutic interventions are supportive and aimed at optimisation of mobility and prevention of cardiac failure. It is recommended to refer the patients to rehabilitation medicine as soon as muscle weakness gives rise to walking difficulties. Physical therapy may prevent contractures that develop in particular when the patient becomes wheelchairbound.
Unlike DMD, there have not been studies on prednisone treatment in BMD. There is, however, one case-report by Higuchi et al. (1993) who describe a favourable response to prednisone as regards myalgia.
Since it is convincingly demonstrated that cardiomyopathy is part of dystrophinopathies, regular follow-up of the cardiologial function is recommended, including Read more
