Caveolinopathies are a small group of neuromuscular diseases associated with dysfunction of a family of proteins located in muscle membrane crevices. The most common caveolinopathy is due to a deficiency of caveolin-3 and results in an autosomal dominant muscular dystrophy and a very specific rippling phenomenon (muscle undulations on contraction or percussion of the muscle). Clinical presentations include proximal myopathy, distal myopathy or persistent high levels of creatine kinase (CK), with widely overlapping phenotypes.
A French study involving several researchers and clinicians from the Institute analysed data from 23 patients with symptomatic CAV3 mutations from 16 different families. They were included in a retrospective cohort. The average length of follow-up was 24.2 ± 15.0 years.
The clinical and functional data collected during follow-up show that :
- exercise intolerance is the most frequent phenotype (52%),
- 80% of patients had calf hypertrophy,
- 65% of patients presented rippling,
- one patient initially presented with camptocormia,
- walking aids were required in only two patients.
In addition, the results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry and Western blot analysis of caveolin-3 compiled show that :
- electroneuromyography was generally normal,
- CK levels were elevated in all patients,
- no patient had cardiac or respiratory disorders,
- muscle imaging showed fatty replacement of many muscles, especially the semimembranosus, semitendinosus, rectus femoris, biceps brachii and spinal muscles.
- The muscle fibres almost always appeared morphologically abnormal (87%) on biopsy, but without any specific lesion.
- Immunohistochemistry of caveolin-3 on biopsy revealed no abnormality in ¼ of patients, whereas Western blots systematically found a reduced quantity of the protein.
- We report nine mutations, four of which have not been described previously.
- No phenotype-genotype correlation was found.
- The authors conclude that caveolinopathy presents in a variety of clinical, histological and muscle imaging forms, but often has limited functional impact. They draw attention to the fact that mild forms of the disease, an atypical phenotype and normal immunostaining for caveolin-3 are pitfalls that lead to misdiagnosis.
Berling E, Verebi C, Venturelli N, Vassilopoulos S, Béhin A, Tard C, Michaud M, Quiles RNV, Vicart S, Masingue M, Carlier RY, Romero NB, Lacene E, Leturcq F, Eymard B, Laforêt P, Stojkovic T. Clinical, histological, and muscle imaging features and follow-up in a multicenter retrospective cohort. Eur J Neurol. 2023 May 11. doi: 10.1111/ene.15832. Epub ahead of print. PMID: 37166430.