Duchenne muscular dystrophy overview
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Differentiating Duchenne muscular dystrophy from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.
Overview
Duchenne muscular dystrophy (DMD) (also known as muscular dystrophy - Duchenne type) is an eventually fatal disorder that is characterized by rapidly progressive muscle weakness and atrophy of muscle tissue. DMD is the most common form of muscular dystrophy. There is no available cure at this time. DMD affects young males due to its X-linked recessive inheritance pattern. Onset of symptoms usually occurs before the sixth year of life and begins with loss of endurance and strength in the legs and pelvis, eventually progressing to include the musculature within the entire body. Two-thirds of DMD incidences are inherited from the mother, while the remaining one-third are caused by mutations in the genes of the egg or embryo. DMD is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806-1875), who first described the disease in the 1860s. It is caused by mutations in the gene which encodes dystrophin, an essential cell membrane protein in muscle cells.
Historical Perspective
Duchenne muscular dystroph y was first discovered by Guillaume Benjamin Amand Duchenne, a French neurologist, in 1860s. The association between genetic mutations and Duchenne muscular dystrophy was made in 1986. In 1987, dystrophin gene on X chromosome were first implicated in the pathogenesis of Duchenne muscular dystrophy.
Classification
There is no established system for the classification of Duchenne muscular dystrophy but according to the Functional Classification System for DMD (AFCSD), there are 5 stages of Duchenne muscular dystrophy based on the gross motor function.
Pathophysiology
It is understood that Duchenne muscular dystrophy is the result of genetic mutation of dystrophin gene located on X-chromosome. Duchenne muscular dystrophy arises from muscle cells, which are involved in muscular contraction. Dystrophin protein is a part of the protein complex named dystrophin-associated protein complex (DAPC) which acts as an anchor that connect the intracellular cytoskeleton proteins such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan to the extracellular matrix. On microscopic histopathological analysis, replacement of muscle by fat and connective tissue, muscle degeneration, muscle regeneration, and opaque hypertrophic fibers are characteristic findings of Duchenne muscular dystrophy.
Causes
Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene which is located on the human X chromosome.
Differentiating Duchenne muscular dystrophy from Other Diseases
Duchenne muscular dystrophy must be differentiated from other diseases that cause muscle weakness, hypotonia, or paralysis such as adult botulism, infant botulism, Guillain-Barre syndrome, Eaton Lambert syndrome, myasthenia gravis, electrolyte disturbance, organophosphate toxicity, tick paralysis, tetrodotoxin poisoning, stroke, poliomyelitis, transverse myelitis, neurosyphilis, multiple sclerosis exacerbation, amyotrophic lateral sclerosis, and inflammatory myopathy.
Epidemiology and Demographics
The incidence of Duchenne muscular dystrophy is approximately 20 per 100,00 births worldwide. In 2010, the prevalence of Duchenne/ Becker muscular dystrophy was estimated to be 1.38 per 10,000 male individuals, ages 5 to 24 years. The mortality rate of Duchenne muscular dystrophy is 100%. The symptoms of Duchenne muscular dystrophy commonly presents in children younger than 5 years of age. Duchenne muscular dystrophy usually affects individuals of the Hispanic race. Non-Hispanic white or black individuals are less likely to develop DMD. Since the disease is X-link recessive, almost all of the patients are male but we may have some female carriers with symptoms as well.
Risk Factors
The most potent risk factor in the development of Duchenne muscular dystrophy is consanguinity marriage.
Screening
There is insufficient evidence to recommend routine screening for Duchenne muscular dystrophy.
Natural History, Complications, and Prognosis
If left untreated, 100% of patients with Duchenne muscular dystrophy may progress to develop heart failure, respiratory failure, and death. Common complications of Duchenne muscular dystrophy include cardiomyopathy with heart failure, respiratory failure, cataracts, decreased movement, depression, contractures, mental impairment, scoliosis, and failure to thrive. Prognosis is generally poor, and the mortality rate of patients with Duchenne muscular dystrophy is approximately 100%.
Diagnosis
Diagnostic Study of Choice
Genetic analysis is the gold standard test for the diagnosis of Duchenne muscular dystrophy.
History and Symptoms
The hallmark of Duchenne muscular dystrophy is muscle weakness. A positive history of a family member with Duchenne muscular dystrophy and history of consanguinity marriage in their parents is suggestive of Duchenne muscular dystrophy. The most common symptoms of muscle weakness specially in the lower limbs, difficulty rising from a sitting position, balance problems, toe walking, grow retardation, clumsiness, frequent falls, multiple fractures, increase the size of the back of the lower leg, curvature of the spine, and breathing problems. Less common symptoms of Duchenne muscular dystrophy include mild cognitive impairment (OCD, anxiety, autism, ADHD) and developmental delay.
Physical Examination
Physical examination of patients with Duchenne muscular dystrophy is usually remarkable for waddling gait, Tachypnea or bradypnea, decreased chest expansion, lordosis, scoliosis, calf muscle hypertrophy, foot drop, tight heel cord, backward bending of the knee, and muscle atrophy in thighs and buttock.
Laboratory Findings
Laboratory findings consistent with the diagnosis of Duchenne muscular dystrophy include increased level of CPK, transaminases, and aldolase.
Electrocardiogram
An ECG may be helpful in the diagnosis of Duchenne muscular dystrophy. Findings on an ECG suggestive of Duchenne muscular dystrophy include tachycardia, shortened PR interval, increased QRS duration, and prolonged QT interval.
X-ray
An x-ray may be helpful in the diagnosis of Duchenne muscular dystrophy. Findings on an x-ray suggestive of Duchenne muscular dystrophy include enlarged heart on x-ray, scoliosis, gracile bones, hypoinflated lungs, and soft tissue translucency (fat tissue).
Echocardiography and Ultrasound
Ultrasound may be helpful in the diagnosis of Duchenne muscular dystrophy. Finding on an ultrasound suggestive of Duchenne muscular dystrophy is increased muscle echogenicity as a result of muscle cells replacement by fat and connective tissue and normal muscle thickness.
CT scan
CT scan may be helpful in the diagnosis of Duchenne muscular dystrophy. Findings on CT scan suggestive of Duchenne muscular dystrophy include fatty infiltration which leads to low attenuation and muscle pseudohypertrophy.
MRI
Lower limb MRI may be helpful in the diagnosis of Duchenne muscular dystrophy. Findings on MRI suggestive of Duchenne muscular dystrophy include high T1-weighted signal in affected muscles.
Other Imaging Findings
There are no other imaging findings associated with Duchenne muscular dystrophy.
Other Diagnostic Studies
Other diagnostic studies for Duchenne muscular dystrophy include genetic testing, muscle biopsy, Electromyography.
Treatment
Medical Therapy
Pharmacologic medical therapies for Duchenne muscular dystrophy include glucocorticoids and disease-modifying treatment.
Interventions
Medical interventions for Duchenne muscular dystrophy include orthopedic intervention, exercise, and multidisciplinary care.
Surgery
Surgical intervention is not recommended for the management of Duchenne muscular dystrophy.
Primary Prevention
There are no established measures for the primary prevention of Duchenne muscular dystrophy.
Secondary Prevention
There are no established measures for the secondary prevention of Duchenne muscular dystrophy.