autosomal recessive limb-girdle muscular dystrophy type 2C

Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is a neuromuscular condition that primarily weakens the muscles around the hips and shoulders. It results from changes in the SGCG gene, which provides instructions for making gamma-sarcoglycan, a protein that helps stabilize muscle cell membranes during movement. Symptoms usually begin in early childhood, and both boys and girls can be affected. The condition is considered rare, affecting roughly one to nine individuals per million people worldwide. Because muscle strength naturally declines over time, early diagnosis and proactive care are important for maintaining mobility and quality of life.

Severity and symptoms vary widely between individuals. In most children, the first noticeable signs are difficulty running, climbing stairs, or rising from the floor, often accompanied by a positive Gowers sign. Progressive weakness of the pelvic and shoulder girdle muscles leads to a waddling or broad-based gait, scapular winging, and eventual loss of independent ambulation. Many children develop calf enlargement, which can represent true hypertrophy or pseudohypertrophy, and some experience lumbar hyperlordosis as they try to compensate for weak core muscles. Respiratory involvement is common over time. Diaphragmatic weakness can cause a restrictive ventilatory pattern, and nighttime breathing difficulties may appear before daytime symptoms are obvious. Cardiac features are less frequent but can include left ventricular systolic dysfunction, so heart evaluation is advised even when no symptoms are present. Electromyography often shows myopathic changes such as positive sharp waves or myotonic discharges, and blood tests may reveal mild to moderate elevations in creatine kinase. Not all individuals experience every feature, and the rate of progression differs from one person to another.

LGMD2C is caused by pathogenic variants in the SGCG gene. Gamma-sarcoglycan is part of the sarcoglycan complex, a group of proteins that links the inside of muscle cells to the surrounding support structure. When gamma-sarcoglycan is missing or defective, muscle fibers become fragile and are damaged with everyday movement, leading to weakness and atrophy. The condition is inherited in an autosomal recessive pattern, meaning an affected individual has two altered copies of SGCG, one inherited from each parent. Parents who each carry a single variant are usually healthy but have a 25 percent chance with each pregnancy of having a child with LGMD2C. The condition is more common when parents share a common ancestor because relatives are more likely to carry the same rare genetic variant. Carrier testing and genetic counseling can help extended family members understand their risks and options for family planning.

Currently, management focuses on supportive care and symptom management. A multidisciplinary team that may include neurologists, cardiologists, pulmonologists, physiatrists, and respiratory therapists coordinates individualized care plans. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Recommended monitoring typically includes annual pulmonary function testing, sleep studies if nighttime hypoventilation is suspected, and periodic cardiac imaging to detect emerging heart muscle weakness. Physical and occupational therapy aim to maintain joint range of motion, delay contractures, and optimize functional independence. Assistive devices such as ankle-foot orthoses, wheelchairs, or adaptive seating are introduced as needed. Non-invasive ventilation at night can support breathing when diaphragm strength declines, and cough-assist devices help clear airway secretions. While no medications are specifically approved for LGMD2C at this time, clinicians may consider general strategies used in other muscular dystrophies on a case-by-case basis. Families should discuss all treatment options with their healthcare team to determine what is most appropriate for their situation.

Outcomes depend on many factors including the rate of muscle weakness, the onset of respiratory involvement, and access to specialized care. Some individuals lose walking ability in early adolescence, while others maintain limited ambulation for a longer period. Assisted ventilation, physical therapy, and proactive cardiac monitoring have improved both quality of life and survival compared with historical reports. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with neuromuscular specialists, genetic counselors, and patient support networks to stay informed about advances in care and research.

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