Duchenne Muscular Dystrophy – Causes And Symptoms

Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is the most common muscular dystrophy with onset in childhood, affecting 1 in 3,300 male newborns, with a prevalence of 63 cases per 1 million.

The disease is genetically transmitted, recessive, X-linked, thus the disease is transmitted to male newborns by mothers who do not develop clinical signs of disease. A third of patients do not have positive family history of disease, suggesting that the disease also occurs by spontaneous mutations. Duchenne disease and Becker phenotype affects almost exclusively males, but Becker phenotype may also rarely occur in women. Also, women with Turner syndrome or with uniparental disomy, or those having chromosome translocations between X chromosomes  and other autosomes may have a similar phenotype to Duchenne phenotype. Elevated levels of creatine phosphokinase meet two thirds of  carrier women, of which most are clinically asymptomatic.

Duchenne muscular dystrophy was first described by Charles Bell in 1830, but Duchenne in 1868 is the one who established diagnostic criteria that are valid today:

• Weakness with onset in the legs;
• Hyperlordosis with wide-based gait;
• Hypertrophy of weak muscles;
• Progressive course over time;
• Reduced muscle contractility on electrical stimulation in advanced stages of the disease;
• Absence of bladder or bowel dysfunction, sensory disturbance, or febrile illness.

Gowers in 1886 concluded the genetic basis of disease, and in 1986 Kunkel identified dystrophin gene mutations that are responsible for disease development. Although remarkable progress has been made in understanding the molecular substrate of the disease, Duchenne muscular dystrophy remains an incurable disease with 100% mortality.

Duchenne Muscular Dystrophy Causes

Duchenne muscular dystrophy is caused by mutations or deletions that destroy large areas or critical segments of the dystrophin gene, causing Duchenne phenotype.

Dystrophin is a protein that is playing  an integral role in the sarcolemma stability (cell membrane of the muscle cell). Dystrophin is associated with transmembrane proteins such as glycoproteins called sracoglycan and dystroglycan forming dystroglycan complex.

Duchenne Muscular Dystrophy – Dystrphin Gene

Muscle fiber integrity is compromised when dystrophin is absent or has apathological structure. Loss of dystrophin function initiates a cascade of events with loss of sarcolemma integrity, and it leads to calcium influx, oxidative cell injury and ultimately myonecrosis (death of muscle fibers). As the disease progresses and destroyed muscle fibers are removed by macrophages, fatty and connective tissue will fill the empty spaces and muscle pseudohypertrophy will appear.

Duchenne Muscular Dystrophy Symptoms

The disease onset is in childhood between the age of 1 year and 5 years, but the first manifestations of disease occur at age 3-4 years, when is observed that the child is clumsy, hardly rises, waddling gait, manifestation that can be the first sign noticed. Some children start walking much later. Gowers sign is described as characteristic: the child uses hands to rise from the floor, bend its trunk, leans with hands on knees, climbing himself, due to lumbar and proximal extremity muscles weakness. At the aged of 4 or 5 years, the child present difficulties to climb on a chair, to climb stairs or to keep standing, compared with other children of his age.

On physical examination is observed lumbar lordosis, wide-based gait, modification that are occurring due to lobar aand pelvic muscles atrophy, paraspinal and abdominal muscles atrophy is leading to a lordotic posture with prominent abdomen. Muscular atrophy that is affecting proximal muscles is symmetrical and bilateral.

Duchenne Muscular Dystrophy – Gowers Sign

Another characteristic of the disease is represented by pseudohypertrophy in certain muscle groups by replacing contractile tissue with hyperplastic connective or fat tissue. False hypertrophy occurring even in early stages of the disease, muscles having a diminished force. Calf hypertrophy typically occurs due to replacement of muscle tissue with fat and connective tissue.

Atrophies and muscle weakness are progressive and are affecting proximal lumbar-pelvic belt, neck extensors muscles, shoulders and arms muscles. In general, neck flexors, wrist extensors, quadriceps, anterior tibial muscle, biceps and triceps are more affected than the neck extensors, arm flexors, deltoid and gastrocnemius.

Tendon reflexes diminish progressively as the muscles became weake. Idio-muscular reflexes diminish early and then disappear. In time, at the age of 10 years are present muscle contractures, tendon retractions with vicious limb position, the patient is immobilized in a wheelchair.

Asymmetric damage of paraspinal muscle causes cifoscoliosis that affect lung function. Respiratory muscle strength begins to decline around the age of 8 years, cough efforts lead to pulmonary atelectasis and favor respiratory infection. Vital capacity decreases gradually and lead to hypoxemia characterized by morning headache and lethargy. There appears no sensitivity problems and muscle fasciculations.

Duchenne Muscular Dystrophy

Dystrophin, the protein whose gene is affected, is also found in heart and brain. The children is mentally retarded and cardiac fibrosis is leading to heart failure and lung congestion, changes in the electrocardiogram and fatal arrhythmias.

Respiratory and cardiac muscles are often affected, respiratory failure or cardiac decompensation are common causes of death in these patients. Usually, these children can not climb stairs around the age of 8-10 years and are immobilized in a wheelchair by the age of 10-12 years. Death often occurs in adolescence before the age of 20 years or between 25 and 30 years.