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Truncation of Caveolin-3 causes autosomal-recessive Rippling Muscle Disease
  1. M Traverso1,
  2. C Bruno1,
  3. A Broccolini2,
  4. F Sotgia3,
  5. M A Donati4,
  6. S Assereto1,
  7. E Gazzerro1,
  8. M Lo Monaco2,
  9. A Modoni2,
  10. A D’Amico2,
  11. S Gasperini4,
  12. E Ricci2,
  13. F Zara1,
  14. M Lisanti3,
  15. C Minetti1
  1. 1
    Muscular and Neurodegenerative Disease Unit, Department of Paediatrics, University of Genoa, G. Gaslini Institute, Genoa, Italy
  2. 2
    Institute of Neurology, Catholic University, Rome, Italy
  3. 3
    Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
  4. 4
    Department of Paediatrics, University of Florence, Florence, Italy
  1. C Minetti, Muscular and Neurodegenerative Disease Unit, Department of Pediatrics, University of Genoa, G. Gaslini Institute, Largo G. Gaslini 5, I-16147 Genoa, Italy; minettic{at}unige.it

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Mutations in the Caveolin-3 gene (CAV3) have been associated with heterogeneous overlapping phenotypes, including: Limb Girdle Muscular Dystrophy type 1C (LGMD-1C), Isolated Elevated Serum Creatine Kinase (HyperCKemia), Distal Myopathy (DM), Rippling Muscle Disease (RMD), Hypertrophic Cardiomyopathy (HCM) and Congenital Long-QT Syndrome (LQTS).1 2

Hereditary RMD is a rare muscle disorder that is characterised by muscle stiffness, exercise-induced myalgias, cramp-like sensations and self-propagating rippling of muscles induced by stretch or percussion. Muscle hypertrophy and increased serum CK levels are also typical features. RMD is usually transmitted in an autosomal-dominant manner, but one homozygous missense mutation (A92T) was recently identified in two patients with a recessive form of RMD.3

Caveolin-3 (Cav-3) is a 22 kDa protein that is composed of 150 amino-acid residues, which are encoded by the CAV3 gene (MIM #601253) on chromosome 3p25.1

Here, we report the clinical, morphological and molecular analysis of a patient with autosomal-recessive RMD carrying two novel compound heterozygous CAV3 mutations that lead to a severe protein truncation.

Case report

At the age of 34 years, a woman was referred to our attention for generalised muscle weakness, exercise-related cramps and myalgias, and hyperCKemia, symptoms that were present since her childhood. Physical examination revealed muscular weakness (particularly severe in the lower limbs), …

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