Limb girdle syndrome

Overview

Limb-girdle syndrome, more commonly referred to as Limb-Girdle Muscular Dystrophy (LGMD), is a group of rare genetic disorders characterized by progressive weakness and wasting of the muscles around the shoulders and hips—the limb-girdle areas. LGMD affects both males and females and typically begins in late childhood to early adulthood, although some forms can appear earlier or later in life. The condition varies widely in severity and progression, depending on the specific subtype and underlying genetic mutation.

Causes

Limb-girdle muscular dystrophy is caused by mutations in genes responsible for the structure and function of muscle fibers. These mutations impair the repair and integrity of muscle tissue, leading to progressive damage and weakness. LGMD is classified based on the affected gene and the pattern of inheritance:

• Autosomal recessive LGMD (LGMD R) – both copies of the gene must be mutated (more common form)

• Autosomal dominant LGMD (LGMD D) – only one copy of the mutated gene is sufficient to cause the disease (less common)

Over 30 different genetic subtypes of LGMD have been identified, each linked to a specific gene defect affecting proteins involved in muscle structure, repair, or signaling.

Symptoms

The symptoms of limb-girdle syndrome vary widely but typically include:

• Progressive muscle weakness – particularly in the hips, thighs, shoulders, and upper arms

• Difficulty climbing stairs or rising from a seated position

• Waddling gait

• Frequent falls

• Scapular winging – protrusion of the shoulder blades

• Muscle wasting – visible reduction in muscle mass

• Joint contractures – tightening of muscles around joints in some subtypes

• Heart and respiratory complications – in certain forms of LGMD

The onset and rate of progression can differ depending on the genetic subtype, with some individuals remaining ambulatory into adulthood and others requiring assistive devices early in life.

Diagnosis

Diagnosis of limb-girdle syndrome involves a combination of clinical evaluation, laboratory tests, imaging, and genetic analysis. Key diagnostic steps include:

• Medical history and physical exam – focusing on muscle weakness patterns and family history

• Creatine kinase (CK) levels – usually elevated in muscle damage

• Electromyography (EMG) – to assess muscle electrical activity

• Muscle biopsy – may show dystrophic changes and help differentiate subtypes

• MRI or CT scan – to visualize muscle involvement and fat replacement

• Genetic testing – essential for confirming the specific LGMD subtype and inheritance pattern

Treatment

There is currently no cure for limb-girdle muscular dystrophy, and treatment focuses on managing symptoms and maintaining mobility and quality of life. Treatment strategies include:

• Physical therapy – to improve strength, flexibility, and prevent contractures

• Occupational therapy – to assist with daily activities and adaptations

• Orthopedic interventions – such as braces or orthopedic surgery for contractures or scoliosis

• Assistive devices – including walkers, canes, or wheelchairs as needed

• Cardiac and respiratory care – including regular monitoring and support in subtypes that affect the heart and lungs

• Corticosteroids or immunosuppressants – may be used in select inflammatory LGMD variants

Gene therapy and other targeted treatments are under investigation in clinical trials for some LGMD subtypes.

Prognosis

The prognosis for individuals with limb-girdle syndrome depends on the specific subtype, age of onset, and progression rate. Some forms are slowly progressive, allowing individuals to lead relatively normal lives with minor disability, while others progress rapidly and result in loss of ambulation and serious complications. Regular follow-up with a multidisciplinary team—including neurology, cardiology, pulmonology, and physical therapy—is essential for optimizing long-term outcomes and quality of life.