Duchenne Muscular Dystrophy

Epidemiology

The prevalence of DMD ranges between 1/3,500-1/ 9,300 male births. The prevalence of BMD varies from 1/16,700 to 1/18,500 male births. The prevalence of symptomatic female carriers is unknown.

Clinical description

Dystrophinopathies present with a spectrum of severity whereby BMD is at the mildest end and DMD the most severe, there is an intermediate phenotype in between. At the mildest end of the spectrum exercise-induced muscle cramps and myoglobinuria may be the only feature while at the severe end, there may be complete loss of muscle function, cardiomyopathy and respiratory failure. DMD presents in early childhood, motor milestones are delayed. Brain involvement leads to cognitive impairment (affecting about a third of patients) and/or pervasive behavioral disorders such as ADHD, autism, anxiety and OCD. Muscle hypertrophy is evident, especially in the calf muscles. Progression is rapid, such that by the age of 5 there is likely to be a waddling gait and positive Gowers’ sign. In untreated boys, walking is lost by 13 years of age (mean 9.5 years). Following loss of ambulation, scoliosis, respiratory failure and cardiomyopathy develop. 

Genetic counseling

The pattern of inheritance is X-linked recessive. Genetic counselling of affected families is recommended and screening of women carriers in the family is important.

Diagnostic methods

The clinical diagnosis can be confirmed by several methods. Creatine Kinase (CK) is very raised. Molecular genetic analysis by MLPA (multiplex ligation-dependent probe amplification) will show a deletion in 60%; full gene sequencing is necessary to identify small deletions, duplications and nonsense mutations. Muscle biopsy for dystrophin analysis which is absent in DMD and reduced in BMD.