Limb–girdle muscular dystrophy

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Limb-girdle muscular dystrophy (LGMD) is a group of genetic and muscular dystrophies that primarily affect the muscles around the pelvis and shoulder girdle. LGMD is characterized by progressive muscle weakness and wasting, which begins in the limbs and can spread to other parts of the body. The condition is caused by mutations in genes responsible for muscle structure and function, leading to the degeneration and weakness of skeletal muscles. The severity, age of onset, and progression of symptoms can vary widely among individuals, even within the same family.

Classification

LGMD is classified into two main types based on the pattern of genetic inheritance: Autosomal dominant (LGMD1) and Autosomal recessive (LGMD2). Each type is further subdivided based on the specific gene that is affected. For example, LGMD1A, LGMD1B, etc., for autosomal dominant forms, and LGMD2A, LGMD2B, etc., for autosomal recessive forms. As of now, numerous subtypes have been identified, each associated with mutations in different genes.

Symptoms

The symptoms of LGMD usually begin in late childhood to early adulthood but can start at any age. The primary symptom is muscle weakness that starts in the hips and shoulders, making it difficult to climb stairs, stand from a seated position, or lift objects. As the disease progresses, muscle weakness and wasting may spread to other parts of the body. Other symptoms may include muscle stiffness, cramping, and in some cases, heart and respiratory problems.

Diagnosis

Diagnosis of LGMD involves a combination of clinical evaluation, family history, muscle biopsy, and genetic testing. Muscle biopsy can reveal characteristic changes in muscle tissue that suggest muscular dystrophy, while genetic testing can identify specific mutations in genes associated with LGMD. Electromyography (EMG) and Creatine kinase levels in the blood may also be used to support the diagnosis.

Treatment

There is currently no cure for LGMD, and treatment focuses on managing symptoms and improving quality of life. Physical therapy and regular exercise may help maintain muscle strength and flexibility. Orthopedic devices such as braces or wheelchairs may be needed to aid mobility. In some cases, surgery may be necessary to correct skeletal deformities. Medications, including corticosteroids, may help slow muscle degeneration. Regular monitoring for heart and respiratory complications is also important.

Prognosis

The prognosis for individuals with LGMD varies widely depending on the subtype and severity of the condition. Some individuals may maintain a high degree of mobility and live a normal lifespan, while others may experience significant disability and have a shortened lifespan due to respiratory or cardiac complications.

Research

Research into LGMD is ongoing, with efforts focused on understanding the genetic causes of the disease, developing gene therapies, and finding effective treatments to slow or stop muscle degeneration. Clinical trials are exploring various approaches, including gene replacement therapy, exon skipping, and stem cell therapy.