Duchenne Muscular Dystrophy is an X-linked recessive muscle disease caused by an inability to synthesize Dystrophin, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, "cardiomyopathy":, and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course.
Duchenne muscular dystrophy is caused by mutations in the DMD gene, which is located on the X chromosome. Due to this, DMD has an incidence of 1 in 3,500 newborn MALES. Mutations within the DMD gene can either be inherited or occur spontaneously during germline transmission.
The main symptom of Duchenne muscular dystrophy is progressive neuromuscular disorder that is muscle weakness associated with muscle wasting with the voluntary muscles being first affected, especially the pelvis and calf muscles. Muscle weakness also occurs in the arms, neck, and other areas, but not as early as in the lower half of the body. Symptoms usually appear before age 6 and may appear as early as infancy. Generalized weakness and muscle wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged.
Main symptoms include:
1. Progressive muscular wasting (weakness)
2. Poor balance
3. Frequent falls
4. Walking difficulty
Other sumpotoms include:
Waddling gait, Calf pain, Limited range of movement, Respiratory difficulty, Drooping eyelids (ptosis), Gonadal atrophy, Scoliosis (curvature of the spine), Inability to walk
Few or none of these symptoms may be present before diagnosis. Some types of muscular dystrophy can affect the heart, causing cardiomyopathy or arrhythmias.
Enigmatically, the extraocular muscles (EOMs) remain clinically unaffected during the course of Duchenne muscular dystrophy. Khurana et al. showed that dystrophin deficiency does not result in myonecrosis or pathologically elevated levels of intracellular calcium in the EOMs. They reported in vitro experiments demonstrating that extraocular muscles are inherently more resistant to necrosis caused by pharmacologically elevated intracellular calcium levels when compared with pectoral musculature. They suggested that the EOMs are spared in DMD because of their intrinsic ability to maintain calcium homeostasis better than other striated muscle groups. This suggested further that modulating levels of intracellular calcium in muscle may be of potential therapeutic use in DMD.
The finding of dystrophin mRNA in brain may bear a relationship to the mental retardation in DMD patients
The muscle-specific isoform of the dystrophin gene is composed of 79 exons, and DNA testing and analysis can usually identify the specific type of mutation of the exon or exons that are affected. DNA testing confirms the diagnosis in most cases.
If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted (usually with a scalpel instead of a needle) and a dye is applied that reveals the presence of dystrophin. Complete absence of the protein indicates the condition.
Over the past several years DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of Duchenne's.
If one or both parents are 'carriers' of a particular condition there is a risk that their unborn child will be affected by that condition. 'Prenatal tests' are carried out during pregnancy, to try to find out if the fetus (unborn child) is affected. The tests are only available for some neuromuscular disorders. Different types of prenatal tests can be carried out after about 11 weeks of pregnancy. Chorion villus sampling (CVS) can be done at 11–14 weeks, and amniocentesis after 15 weeks, while fetal blood sampling can be done at about 18 weeks. Women and/or couples need to consider carefully which test to have and to discuss this with their genetic counselor. Earlier testing would allow early termination, but it carries a slightly higher risk of miscarriage than later testing (about 2%, as opposed to 0.5%).
Duchenne muscular dystrophy is caused by a mutation of the dystrophin gene at locus Xp21.Approximately two-thirds of the mutations are deletions of one or many exons in the dystrophin gene. Although there is no clear correlation found between the extent of the deletion and the severity of the disorder, DMD deletions usually result in frameshift. Dystrophin is responsible for the connection of muscle fibers to the extracellular matrix through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (cell membrane). In a complex cascading process that involves several pathways and is not clearly understood, increased oxidative stress within the cell damages the sarcolemma, and eventually results in the death of the cell. Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue.