LAUSR

BACKGROUND CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or an isolated persistent high creatine kinase (CK) with a major overlapping phenotype. METHODS Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography and muscle histopathology and immunohistochemistry and caveolin-3 Western blot analysis were also compiled. RESULTS Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy and only 65% of patients presented a rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. While a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype-genotype correlation was evidenced. CONCLUSIONS Caveolinopathy have diverse clinical, muscle imaging and histological presentations but often have limited functional impact. Mild forms of the disease, an atypical phenotype and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis.