Limb-girdle muscular dystrophy is a term for a group of 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, and thighs.

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. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.

In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.

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 limb-girdle muscular dystrophy.

Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. 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).

Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.

The various forms of limb-girdle muscular dystrophy are caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in muscle maintenance and repair.

Some of the proteins produced from these genes assemble with other proteins into larger protein complexes. These complexes maintain the physical integrity of muscle tissue and allow the muscles to contract. Other proteins participate in cell signaling, cell membrane repair, or the removal of potentially toxic wastes from muscle cells.

Limb-girdle muscular dystrophy is classified on the basis of its inheritance pattern and genetic cause. Limb-girdle muscular dystrophy type 1 includes forms of the disorder that have an inheritance pattern called autosomal dominant. Limb-girdle muscular dystrophy type 2 includes forms of the disorder that have an inheritance pattern called autosomal recessive.

Calpainopathy, or limb-girdle muscular dystrophy type 2A, is caused by mutations in the CAPN3 gene. Type 2A is the most common form of limb-girdle muscular dystrophy, accounting for about 30 percent of cases. Dysferlinopathy, also called limb-girdle muscular dystrophy type 2B, is caused by mutations in the DYSF gene.

Sarcoglycanopathies are forms of limb-girdle muscular dystrophy caused by mutations in the SGCA, SGCB, SGCG, and SGCD genes. These sarcoglycanopathies are known as limb-girdle muscular dystrophy types 2D, 2E, 2C, and 2F respectively.

A TTN gene mutation causes limb-girdle muscular dystrophy type 2J, which has been identified only in the Finnish population. Mutations in the ANO5 gene cause limb-girdle muscular dystrophy type 2L. Mutations in several other genes cause forms of limb-girdle muscular dystrophy called dystroglycanopathies, including limb-girdle muscular dystrophy types 2I, 2K, 2M, and 2N.

Other rare forms of limb-girdle muscular dystrophy are caused by mutations in several other genes, some of which have not been identified. In addition, for certain forms that are classified by some researchers as limb-girdle muscular dystrophy, other researchers propose grouping them with different, related disorders, such as myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, rippling muscle disease, or Pompe disease.

Limb-girdle muscular dystrophy type 1B (LGMD1B) is one of many types of limb-girdle muscular dystrophy. These diseases affect the voluntary muscles, which are the muscles that are moved on purpose, such as thearms, legs, fingers, toes, and facial muscles. Specifically, LGMD1B causes muscle weakness in the lower limbs. The muscle weakness typically affects themuscles closest to the center of the body (proximal muscles) such as the upperlegs. The disease is progressive, leading to a loss of muscle strength and bulkover a number of years.

Limb-girdle muscular dystrophy type 1B is caused by mutations (changes) to the LMNA gene. The disease is inherited in an autosomal dominant manner. A diagnosis of LGMD1B is suspected in people who have signs and symptomsconsistent with the disease, and the diagnosis can be confirmed with laboratorytests. While there are not treatments that can reverse the muscle weakness associated with the disease, supportive treatment can decrease the complications.

• Pelvifemoral limb-girdle muscular dystrophy (also known as Leyden-Mobius LGMD) is the most frequently observed subtype. In these cases, muscle weakness is first evident in the pelvic girdle and later in the shoulder girdle. Onset is usually before age 12 or after age 30;
• Scapulohumeral LGMD (also known as Erb LGMD) usually has milder symptoms with infrequent early onset. In most cases, muscle weakness is first evident in the shoulder girdle and later in the pelvic girdle;
• HyperCKemia is usually observed in children or young individuals. In most cases, those affected do not have symptoms, just high levels of creatine kinase in their blood.

Limb-girdle muscular dystrophy type 2C (LGMD2C) is a genetic condition that affects the voluntary muscles around the hips and shoulders. This condition belongs to a group of muscle disorders called limb-girdle muscular dystrophies, which are characterized by progressive loss of muscle bulk and symmetrical weakening of voluntary muscles. Symptoms of LGMD2C usually appear around 6-8 years of age, may be mild or severe, and can progress to loss of the ability to walk by 12-16 years. Symptoms may additionally include: enlargement (hypertrophy) of the calf muscle and tongue, diseases of the heart muscle (cardiomyopathy), and respiratory abnormalities.

LGMD2C is caused by mutations in the SGCG gene and is inherited in an autosomal recessive manner. Although there is no specific treatment or cure for LGMD2C, there are ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person.

Limb-girdle muscular dystrophy type 2I (LGMD2I) is a form of limb-girdle muscular dystrophy, which refers to a group of conditions that cause weakness and wasting of the muscles in the arms and legs. The proximal muscles (those closest to the body such as the upper arms and thighs) are generally most affected by the condition. In LGMD2I, specifically, signs and symptoms often develop in late childhood (average age 11.5 years) and may include difficulty running and walking. The symptoms gradually worsen overtime and affected people generally rely on a wheelchair for mobility approximately 23-26 years after onset.

LGMD2I is caused by changes (mutations) in the FKRP gene and is inherited in an autosomal recessive manner. There is, unfortunately, no cure for LGMD2I and treatment is based on the signs and symptoms present in each person.

It is difficult to determine the prevalence of limb-girdle muscular dystrophy because its features vary and overlap with those of other muscle disorders. Prevalence estimates range from 1 in 14,500 to 1 in 123,000 individuals.