Muscular dystrophies are an inherited group of primary diseases
of muscle, characterized pathologically by muscle fiber degeneration and
clinically by progressive muscle weakness. Pathologic, clinical and
genetic criteria have been used as the basis for their classification.
Muscular Dystrophies (Dystrophinopathies)
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy
(BMD) are progressive myopathies, inherited as X-linked recessive
traits. DMD is the most common form of muscular dystrophy, with
an incidence of about 1 in 3300 live male births and a prevalence
rate in the total population of about 3 per 100,000. BMD has a similar
presentation but a relatively milder clinical course. The reported
incidence of BMD has varied from about 1 in 18,000 to 1 in 31,000
male births. In addition, there is an intermediate group of patients
with either mild DMD or severe BMD, who are known as outliers. It
is now well known that all 3 types of muscular dystrophy are allelic,
resulting from dystrophin deficiency due to mutations of a single
gene, called the dystrophin gene.1
Other dystrophinopathies, occurring at a lower incidence, include:
- manifesting DMD/BMD carrier females,
- X-linked dilated cardiomyopathy, and
- muscle cramps with myoglobinuria.
Great heterogeneity in the clinical features and course of the
various dystrophinopathies has been observed, creating a spectrum
ranging from very mild to very severe presentations. The severe
end of the spectrum includes DMD, BMD the outliers or intermediate phenotype
in which skeletal muscle is primarily affected, and X-linked dilated
cardiomyopathy in which the heart is the organ primarily affected.
Females who carry DMD/BMD can be totally asymptomatic or
can manifest mild to severe symptoms.
Clinically, the distinction between DMD and BMD is made by the
age of wheelchair confinement, which is less than 13 years in DMD
and beyond 16 years in BMD. Patients who become wheelchair-bound
between 13 years and 16 years are classified as outliers or as exhibiting
an intermediate presentation. The outlier group could be classified clinically
as having either mild DMD or severe BMD.
In children with Duchenne muscular dystrophy (DMD), although there
is histologic and laboratory evidence of myopathy from birth, the
onset of weakness usually occurs between 2 and 3 years of age; it
may be delayed and become apparent after the age of 3 years, but almost
all patients with DMD become symptomatic before age 5 years. The
child usually has difficulty with running, jumping, going up steps,
and other similar activities; an unusual waddling gait, lumbar lordosis,
and calf enlargement are usually observed. Muscular weakness is
symmetrical and selectively affects proximal limb muscles before
distal and the lower extremities before the upper. Early on, the
patient may complain of leg pains. Jumping and running are almost
impossible in most cases, and, in arising from the floor, affected
boys use hand support ...