Muscular Dystrophy is a group of disorders that affects the musculoskeletal system. It is progressive disorder that comes about from defected genes that are necessary for the growth and function of muscles. Two types that are caused from a defect in the dystrophin gene are Duchenne and Becker muscular dystrophy, and they are inherited as X-linked recessive traits.
Dunchenne muscular dystrophy, DMD, is resulted from a defect in the gene that produces dystrophin. Dystrophin is located on the plasma membrane of the muscle fibers and functions as part of a glycoprotein complex providing stability and reinforcement which helps stops the muscles from degrading. When these membrane proteins are not there, the muscle fibers can degenerate and lead to weakness in the muscles. In Wales, the prevalence of DMD that was detected in a newborn was 1 in 5867 live male births, and in the US the population based surveillance study of males from ages five to twenty four living in either Arizona, Colorado, Iowa and New York showed a prevalence of 1.3 to 1.8 in every 10,000 for DMD and BMD(Becker muscular dystrophy).
DMD can also cause cardiomyopathy, where the posterbasal left ventricular wall of the heart is affected by extensive fibrosis, and this fibrosis can spread to the lateral free wall of the left ventricle. This incidence of cardiomyopathy in patients with DMD increases as the patient increases into their teenage years. Other complication that are involved in DMD are frequent fractures with the arms and legs due to cases like falling. A series of patients from one to twenty-five found that 21 percent of the patients suffered from fractures. Scoliosis also progressively develops in most children with DMD, and can lead to impaired respiratory and pulmonary function if paired with progressive weakness.
A physical examination can reveal lumbar lordosis, a waddling gait, shortening of the Achilles tendons and swollen calf and quadriceps muscles with indication of deposits of fat and fibrous tissue. By the age of twelve, patients with DMD are usually confined to a wheelchair and die in late teens or early twenties due to cardiomyopathy or respiratory failure.
Becker muscular dystrophy patients usually see symptoms later in life compared to DMD patients. They do not have trouble walking or need assistance with walking until the earliest fifteen, and most commonly into adulthood. Muscle involvement is less severe in BMD, however, cardiac problems may be more evident due to the fact that since a patient can sustain strenuous exercise it is putting more stress on their heart resulting in harmful effects towards to myocardial cells lacking dystrophin.
When diagnosing DMD and BMD a multitude of test can be performed. We can test for elevated levels of serum creatine kinase, looking for electrocardiogram and electromyography abnormalities, and skeletal muscle biopsies which will all yield similar results for both Duchenne and Becker muscular dystrophy. To distinguish which form it is, we must look at the difference is dystrophin levels in the skeletal muscles. Dystrophin immunoblotting is a way people figure out the severity of the muscular dystrophy, and looks at the quantity of the dystrophin molecule which in turn determines the severity of DMD while qualitative changes of dystrophin involves the expression of BMD. To fully investigate this diseases a thorough history, physical examination, and laboratory analysis of muscle enzymes are used. This diagnoses is affected by age, sex, presence of symptoms of myopathic processes, increased creatine kinase, myoptic changes in muscle biopsy and electromyography, and positive family history showing X-linked recessive inheritance. There is also a genetic analysis where you can test genes of patients with an elevated serum CK levels. There are multiple types of tests that can be performed for the analysis of the DMD gene which include analysis for deletions/duplications, which is the most common form of mutations, and mutation scanning and sequence analysis to detect point mutations. In sporadic cases, a patient that shows signs of that may indicate DMD or BMD without a family history should be genetic tested for mutations in the DMD gene and this should be performed first. The reason for this is if the test is positive it will confirm DMD, but if it is negative another test will be performed targeting certain gene mutations that will cause limb-girdle muscular dystrophy, a type of MD that causes weakness and deterioration in muscles of the proximal muscles of the arms and legs including shoulders, upper arms, pelvic area and thighs. If this test is negative we will move on to a muscle biopsy for histology.
Males are usually affected but 2.5 to 20 percent of female carriers can have muscle weakness with the muscular dystrophy gene. Females are susceptible to early onset MD but usually need to be combined with another genetic abnormality which can include an abnormality of the 45X, 46XY, or tumor mosaic karyotypes.