Limb-girdle muscular dystrophy (LGMD) is a group of monogenic diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, thighs, and, occasionally, the heart. Signs and symptoms often present in adolescence and generally worsen with time. As the condition progresses, people with LGMD may eventually require wheelchair assistance. In more severe cases, premature death can occur as early as 30 years of age.
Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with LGMD.
Weakening of the heart muscle (cardiomyopathy) occurs in some forms of LGMD. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).
Affecting males and females globally, each LGMD subtype results from a single mutation in genes that affect proteins necessary for normal muscle function. The NIH estimates total LGMD prevalence between 1 in 14,500 to 1 in 123,000 individuals, affecting ~16,000 patients combined in the US. The prevalence of each LGMD subtype ranges from 2 – 10 per million, or 1,000 – 10,000 patients in the US and EU combined.
There are currently no cures or effective therapies for LGMDs.