autosomal recessive limb-girdle muscular dystrophy type 2B

Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) is a genetic muscle disorder that primarily weakens the large muscles around the hips and shoulders. It results from pathogenic variants in the DYSF gene, which encodes dysferlin, a protein essential for repairing muscle cell membranes. Symptoms usually begin in late adolescence or early adulthood and affect people of all sexes. The condition is rare, affecting roughly 1 to 9 individuals per million people worldwide. Although muscle weakness progresses over time, the heart and breathing muscles are generally spared.

LGMD2B most visibly affects skeletal muscles. Early or presenting signs often include difficulty running, climbing stairs, or rising from the floor because of proximal muscle weakness. Calf muscles may appear unusually large (hypertrophy), and blood tests typically show markedly elevated creatine kinase levels, hinting at ongoing muscle damage. As the condition evolves, muscle atrophy can spread to the arms and legs, and many individuals eventually need a wheelchair for longer distances. Less common features include neck flexor weakness, scapular winging, hyperlordosis, pes cavus, and reduced tendon reflexes. Cardiac involvement is uncommon, but some people develop conduction changes such as right bundle branch block or mild ventricular enlargement, so careful follow-up is advisable. Not all individuals experience all features, and severity varies considerably.

LGMD2B is caused by biallelic (two-copy) pathogenic variants in the DYSF gene. Dysferlin helps patch tiny tears in the muscle cell membrane that occur during normal activity; without it, cells accumulate damage and gradually lose function. The disorder is inherited in an autosomal recessive pattern, meaning a child must receive one altered DYSF gene from each parent to be affected. Parents who each carry one altered copy are typically healthy but have a 25 percent chance with each pregnancy of having a child with LGMD2B. This condition is more common when parents share a common ancestor because relatives have a higher likelihood of carrying the same rare genetic variant. Carrier testing and genetic counseling are recommended for at-risk relatives and for family planning. Even within affected families, the age of onset and rate of progression can differ (variable expressivity).

Currently, management focuses on supportive care tailored to each individual’s needs. Customized physical and occupational therapy programs help maintain muscle strength, joint flexibility, and functional independence, while orthotic devices or mobility aids can ease daily activities as weakness progresses. Regular surveillance by a multidisciplinary team, including neuromuscular specialists, physiatrists, orthopedic physicians, and when indicated cardiologists, allows ongoing monitoring of muscle function, joint complications, and rare cardiac conduction changes. Respiratory assessments may be added if significant trunk or diaphragm weakness emerges. Although no disease-specific therapies are yet available, participation in rehabilitation programs, optimization of nutrition and weight, and proactive management of pain or contractures can improve quality of life. Patients should review emerging research studies with their healthcare providers to determine whether investigational options or clinical trials may be appropriate.

LGMD2B is usually slowly progressive. Many individuals maintain independent walking for years after symptoms begin, though a substantial number eventually transition to wheelchair use, especially for long distances. Because the heart and breathing muscles are generally not severely affected, life expectancy can be near normal for many people who receive appropriate supportive care. Severity and progression vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with neuromuscular clinics, genetic counselors, and patient registries that track long-term health and support access to emerging therapies.

Several clinical trials are currently investigating new treatment strategies, including gene-based and other investigational approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.