Anoctamin-5-related limb-girdle muscular dystrophy R12

Anoctamin-5-related limb-girdle muscular dystrophy R12 (LGMDR12), formerly known as limb-girdle muscular dystrophy type 2L (LGMD2L), is a rare inherited muscular dystrophy caused by biallelic pathogenic variants in the ANO5 gene (also known as TMEM16E), which encodes the anoctamin-5 protein. This protein is thought to function as a calcium-activated chloride channel and plays a role in muscle membrane repair. The disease primarily affects the skeletal muscular system, leading to progressive proximal muscle weakness predominantly involving the pelvic girdle and lower limbs. Patients typically present in adulthood, often in the second to fourth decade of life, with difficulty walking, climbing stairs, and rising from a seated position. Asymmetric muscle involvement is a notable feature, and calf muscles may show early and prominent wasting. Serum creatine kinase (CK) levels are usually markedly elevated, sometimes even before the onset of clinical weakness. The clinical spectrum of ANO5-related muscle disease is broad and also includes Miyoshi muscular dystrophy type 3 (MMD3), a distal myopathy phenotype with predominant calf involvement, and asymptomatic or pauci-symptomatic hyperCKemia. In LGMDR12, disease progression is generally slow, and most patients remain ambulatory for many years, though some may eventually require wheelchair assistance. Cardiac involvement is uncommon but has been reported in rare cases. Respiratory function is generally preserved. Muscle MRI typically shows fatty infiltration of the posterior thigh compartment muscles (adductor magnus, semimembranosus, biceps femoris) and medial gastrocnemius. Diagnosis is confirmed through genetic testing identifying biallelic ANO5 mutations, supported by clinical findings, elevated CK, and characteristic MRI patterns. Muscle biopsy shows dystrophic changes but is not specific. Currently, there is no disease-specific or curative treatment for LGMDR12. Management is supportive and includes physical therapy, occupational therapy, orthopedic interventions as needed, and monitoring of cardiac and respiratory function. Research into potential therapies is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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