E.A.C. Beenakker, M.D.
Initial complaints in most boys with DMD are an abnormal gait with toe walking, frequent falls and difficulties with climbing stairs. There is often a history of delayed achievement of motor milestones. The mean age at diagnosis is between 4 and 5 years (Mohamed K et al. 2000; Crisp et al, 1982; Felisari et al., 2000), when proximal weakness is sufficiently severe to produce a waddling gait and problems with rising from the floor.On physical examination one may find mild proximal weakness in the lower limbs with a Gowers sign, shortened ankle tendons and tendon reflexes that are still present. There is compensatory lumbar hyperlordosis which disappears when the child is sitting. The calf muscles are large and feel quite firm or even rubbery due to replacement of muscle fibres by fibrofatty tissue. Besides muscle weakness mental impairment is present in DMD (Cohen et al., 1968). Approximately 33% of the patients has an intelligence quotient - score below 75 (Bresolin et al., 1994).
The diagnosis of DMD is based on clinical signs and symptoms and confirmed by raised serum concentration of creatine kinase (CK) (Zatz et al., 1991), absence of dystrophin in muscle biopsy (Bakker et al., 1997), and the finding of a mutation in the dystrophin gene.
The muscle biopsy shows abnormalities typical of muscular dystrophy such as necrosis and attempted regeneration of individual muscle fibres, increased variability of muscle fibre diameter with both hypertrophic and small fibres, and central nuclei. In an end-stage biopsy, almost the entire muscle is replaced by fibrofatty tissue.
To confirm the clinical diagnosis immunohistochemical analysis of the muscle biopsy is usually performed.
If this shows complete absence or severe reduction of dystrophin with only an occasional fibre (less than 5%) staining positively (Bakker et al., 1997), further genetic analysis is performed.
DMD must be differntiated from Becker muscular dystrophy (BMD), which is caused by mutations in the same gene but has a milder phenotype.
In all DMD patients serum CK is raised from birth onwards and exceeds at least 10 times the normal upper limit (Zatz et al., 1991). After 5 years of age the concentration slowly declines.
There is no cure for DMD. Treatment goals are to maintain function, prevent contractures, and provide psychological support to the child and its family. Main efforts should be directed towards keeping these children standing and walking as long as possible. Passive stretching exercises, use of splints to maintain the feet in an neutral position during the night, and use of long-leg braces for walking are important in this respect. Scoliosis can not be prevented and, if progressive, surgical correction is the only effective way to straighten the spine.
Steroids do have a beneficial effect on muscle force and muscle function, but their use is not yet generally accepted because of uncertainties about both the positive and negative effects on the long run.
Other treatments aiming at the correction of the gene defect itself are not yet available for clinical use.