Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of muscular dystrophies characterized by proximal weakness affecting the pelvic and shoulder girdles. Occasionally, the heart (cardiac) and breathing (respiratory) muscles may be affected. The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Onset may occur in childhood, adolescence, young adulthood, or even later. Males and females are affected in equal numbers. LGMD incidence ranges from 1 in 14,500 to 1 in 123,000 individuals.
LGMD is caused by mutations in genes that result in abnormal function of proteins in muscles, thereby causing progressive muscle weakness. The inheritance pattern of LGMD varies and different genetic defects may result in the same clinical symptoms in different patients. Sometimes, no obvious inheritance pattern can be identified. As of late 2012, there are more than 20 different subtypes of LGMD, and this is a complex and constantly evolving area of research. Type 1 LGMDs are dominantly inherited, requiring only one mutation for symptoms to result. Type 2 LGMDs are recessively inherited, requiring two mutations — one from each parent — for symptoms to appear. Sometimes, LGMDs are referred to by their names, not their numbers, and some types have not been assigned numbers.
Researchers have identified many different subtypes of LGMD, each one resulting from a mutation of a different disease gene (genetic heterogeneity). The genes associated with many of these subtypes have been identified. Most of these genes are involved in the production of certain muscle proteins. These proteins may be located on the membrane surrounding each muscle cell or within the cell itself. The membrane surrounding each muscle cell, known as the sarcolemma, protects the cells from injury and serves as a gate that allows or prevents substances into the cell. If one of the proteins is missing or defective, muscle cells may be damaged or may incorrectly allow substances in or out of the cell, eventually resulting in the symptoms of LGMD. The exact role and function of all these proteins and how their deficiency or absence causes LGMD is not yet known.
The signs and symptoms of a limb-girdle muscular dystrophy can vary widely, even among individuals within the same family. Symptoms may begin at any age.
- Toe walking or walking on the balls of the feet
- Walking with a waddling gait
- Inability to rise from a squatting position without using the arms for leverage
- Difficulty running
- Abnormal curvature of the spine, such as lordosis and scoliosis.
- Joint stiffness
The diagnosis of LGMD is based on the clinical history, including a family history, physical examination and supporting laboratory studies. For some of the LGMDs, it is possible to make a definitive diagnosis by a blood test to determine the specific genetic defect responsible for symptoms. In other situations, additional laboratory studies are necessary to make a diagnosis including electrodiagnostic testing (EMG), muscle imaging with CT or MRI to show patterns of muscle involvement and muscle biopsy. Muscle biopsy is often helpful to determine if weakness is caused by muscular dystrophy, an inherited disorder, or by other acquired causes of muscle degeneration such as from inflammation or toxic exposure. Investigations may also include looking into Serum CK levels, which may often be raised in LGMD. DNA analysis is considered the gold standard test, but its feasibility varies for different types of LGMD and required specialist laboratories.
Treatment of LGMD remains palliative and supportive and includes weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and prevent contractures, use of mechanical aids to help ambulation and mobility, surgical intervention for orthopedic complications, use of respiratory aids when indicated, monitoring for cardiomyopathy in LGMD types with cardiac involvement, and social as well as emotional support and stimulation.
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