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HEREDITARY MONOGENIC DISEASES

           

Limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy refers to a group of more than 30 genetic diseases that cause weakness and progressive degeneration of the skeletal muscles used during voluntary movement. These disorders vary in the patient´s age at the time of onset, severity and the muscle pattern affected. All forms of muscular dystrophy worsen as the muscles degenerate and progressively weaken. The majority of patients finally use the ability to walk.

Some types of muscular dystrophy also affect the heart, the gastrointestinal system, the endocrine glands, the spinal column, eyes, brain and other organs. Respiratory and cardiac illnesses are common and some patients experience problems swallowing.

Muscular dystrophy can affect various tissues and organs of the body, especially the integrity of the muscle fibers. The disease causes muscle degeneration, progressive weakness, fiber death, fiber branching and splitting, phagocytosis (in which muscle fiber material is broken down and destroyed by scavenger cells), and, in some cases, chronic or permanent shortening of tendons and muscles. Also, overall muscle strength and tendon reflexes are usually lessened or lost due to replacement of muscle by connective tissue and fat. It is not contagious, nor can it be brought on by a lesion.

MD occurs worldwide, affecting all races. Its incidence varies, as some forms are more common than others. Its most common form in children, Duchenne muscular dystrophy, affects approximately 1 in every 3,500 to 6,000 male births each year in the United States.** Some types of MD are more prevalent in certain countries and regions of the world. Many muscular dystrophies are familial, meaning there is some family history of the disease. Duchenne cases often have no prior family history. This is likely due to the large size of the dystrophin gene that is implicated in the disorder, making it a target for spontaneous mutations.

There are nine major groups of the muscular dystrophies. The disorders are classified by the extent and distribution of muscle weakness, age of onset, rate of progression, severity of symptoms, and family history (including any pattern of inheritance). Although some forms of MD become apparent in infancy or childhood, others may not appear until middle age or later.

Limb-girdle muscular dystrophy

Limb-girdle MD (LGMD) refers to more than 20 inherited conditions marked by progressive loss of muscle bulk and symmetrical weakening of voluntary muscles, primarily those in the shoulders and around the hips. At least 5 forms of autosomal dominant limb-girdle MD (known as type 1) and 17 forms of autosomal recessive limb-girdle MD (known as type 2) have been identified. Some autosomal recessive forms of the disorder are now known to be due to a deficiency of any of four dystrophin-glycoprotein complex proteins called the sarcoglycans.

The recessive LGMDs occur more frequently than the dominant forms, usually begin in childhood or the teenage years, and show dramatically increased levels of serum creatine kinase. The dominant LGMDs usually begin in adulthood.

In general, the earlier the clinical signs appear, the more rapid the rate of disease progression. Limb-girdle MD affects both males and females. Some forms of the disease progress rapidly, resulting in serious muscle damage and loss of the ability to walk, while others advance very slowly over many years and cause minimal disability, allowing a normal life expectancy. In some cases, the disorder appears to halt temporarily, but progression then resumes.

Weakness is typically noticed first around the hips before spreading to the shoulders, legs, and neck. Individuals develop a waddling gait and have difficulty when rising from chairs, climbing stairs, or carrying heavy objects. They fall frequently and are unable to run. Contractures at the elbows and knees are rare but individuals may develop contractures in the back muscles, which gives them the appearance of a rigid spine. Proximal reflexes (closest to the center of the body) are often impaired. Some individuals also experience cardiomyopathy and respiratory complications, depending in part on the specific subtype. Intelligence remains normal in most cases, though exceptions do occur. Many individuals with limb-girdle MD become severely disabled within 20 years of disease onset.

PREVENTION

Muscular dystrophy is an inherited disease. Parents who wish to have children should consult with a genetic specialist if they are worried about the possibility of passing the disease on to the child, especially if one of the parents has muscular dystrophy or has a family history of the disorder-one is a carrier of the gene.

GENE OR REGION STUDIED


  • SGCA
  • FKRP