French National Protocol for Diagnosis and Care of Calpainopathy (LGMD R1/LGMD D4): consensus guidelines for clinical practice

Calpainopathies, including limb-girdle muscular dystrophy recessive type 1 (LGMD R1) and the rare dominant type 4 (LGMD D4), are genetic neuromuscular disorders caused by pathogenic variants in the CAPN3 gene, which encodes calpain-3, a muscle-specific cysteine protease. This protein plays a crucial role in muscle remodelling, calcium homeostasis, and myogenesis regulation. LGMD R1, the most common form of LGMD, is characterized by progressive, symmetrical muscle weakness primarily affecting the shoulder and pelvic girdles, with an onset ranging from childhood to adulthood. It affects about 1 in 100,000 individuals. The clinical spectrum is wide, with three main phenotypes: pelvifemoral myopathy, scapulohumeral myopathy, and isolated hyperCKemia. LGMD D4 is characterized generally by a milder phenotype with variable but frequent axial muscle involvement. Diagnostic algorithm include serum CK levels dosage, muscle imaging, and sometimes a muscle biopsy, with definitive diagnosis confirmed by CAPN3 gene testing. Calpainopathies have no cure and care is focused on physiotherapy, management of muscle contractures, moderate physical activity, and orthosis. The newly established French National Diagnosis and Care Protocol (NDCP) aim to standardize the diagnosis and care of calpainopathies. The protocol emphasizes early diagnosis, personalized patient care, genetic assessment and prevention of disease progression. This initiative aims to reduce diagnostic delays and improve patient outcomes through a harmonized multidisciplinary approach, informed by the latest clinical and research expertise.