Rippling associated with a variant in the CAV3 gene in a Peruvian child: a case report
DOI:
https://doi.org/10.59594/iicqp.2026.v4n1.164Keywords:
Caveolin-3, Muscle Rigidity, Myalgia, Muscular DiseasesAbstract
Background: Caveolinopathies are diseases primarily caused by variants in the CAV3 gene (caveolin-3), affecting skeletal muscle, cardiac muscle, or both.
Case description: We describe the case of a 6-year-old Peruvian boy who presented with muscle stiffness, myalgia, rippling, and hyperCKemia. Clinical examination revealed calf hypertrophy, Achilles tendon contractures, and toe walking. Next-generation sequencing analysis identified the previously reported heterozygous pathogenic variant c.99C>G (p.Asn33Lys) in CAV3. Segregation studies in affected family members were consistent with an autosomal dominant inheritance pattern.
Conclusions: This case illustrates the phenotypic variability of caveolinopathies and highlights the importance of considering this diagnosis in patients with myalgia and rippling beginning in the first decade of life. Although clinical findings guide the diagnosis, genetic confirmation is necessary to provide timely family counseling.
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Gazzerro E, Sotgia F, Bruno C, Lisanti MP, Minetti C. Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet. 2010;18(2):137-45. doi: 10.1038/ejhg.2009.103
Pradhan BS, Prószyński TJ. A Role for Caveolin-3 in the Pathogenesis of Muscular Dystrophies. Int J Mol Sci. 2020;21(22):8736. doi: 10.3390/ijms21228736
Benzoni P, Gazzerro E, Fiorillo C, Baratto S, Bartolucci C, Severi S, et al. Caveolin-3 and Caveolin-1 Interaction Decreases Channel Dysfunction Due to Caveolin-3 Mutations. Int J Mol Sci. 2024;25(2):980. doi: 10.3390/ijms25020980
Phillips L, Trivedi JR. Skeletal Muscle Channelopathies. Neurotherapeutics. 2018;15(4):954-65. doi: 10.1007/s13311-018-00678-0
Fulizio L, Nascimbeni AC, Fanin M, Piluso G, Politano L, Nigro V, et al. Molecular and muscle pathology in a series of caveolinopathy patients. Hum Mutat. 2005;25(1):82-9. doi: 10.1002/humu.20119
Sugie K, Murayama K, Noguchi S, Murakami N, Mochizuki M, Hayashi YK, et al. Two novel CAV3 gene mutations in Japanese families. Neuromuscul Disord. 2004;14(12):810-4. doi: 10.1016/j.nmd.2004.08.008
ClinVar [Internet]. Bethesda (MD): National Center for Biotechnology Information; variante NM_033337.3(CAV3):c.99C>G (p.Asn33Lys) – RCV000539792. [citado el 22 de diciembre de 2025]. Disponible en: https://www.ncbi.nlm.nih.gov/clinvar/RCV000539792/
Gazzerro E, Bonetto A, Minetti C. Caveolinopathies: translational implications of caveolin-3 in skeletal and cardiac muscle disorders. Handb Clin Neurol. 2011;101:135-42. doi: 10.1016/B978-0-08-045031-5.00010-4
Chen J, Zeng W, Han C, Wu J, Zhang H, Tong X. Mutation in the caveolin-3 gene causes asymmetrical distal myopathy. Neuropathology. 2016;36(5):485-9. doi: 10.1111/neup.12297
Berling E, Verebi C, Venturelli N, Vassilopoulos S, Béhin A, Tard C, et al. Caveolinopathy: Clinical, histological, and muscle imaging features and follow-up in a multicenter retrospective cohort. Eur J Neurol. 2023;30(8):2506-17. doi: 10.1111/ene.15832
Renard D, Erny F, Figarella-Branger D, Krahn M. Calf hypertrophy and gastrocnemius MRI short tau inversion recovery (STIR) hyperintensity in a patient with asymptomatic hyperCKemia caused by caveolin-3 gene mutation. Neuromuscul Disord. 2016;26(4-5):326-7. doi: 10.1016/j.nmd.2016.02.009
Ohsawa Y, Ohtsubo H, Saito Y, Nishimatsu SI, Hagiwara H, Murakami T, et al. Caveolin 3 suppresses phosphorylation-dependent activation of sarcolemmal nNOS. Biochem Biophys Res Commun. 2022;628:84-90. doi: 10.1016/j.bbrc.2022.08.066
Shah DS, Nisr RB, Stretton C, Krasteva-Christ G, Hundal HS. Caveolin-3 deficiency associated with the dystrophy P104L mutation impairs skeletal muscle mitochondrial form and function. J Cachexia Sarcopenia Muscle. 2020;11(3):838-58. doi: 10.1002/jcsm.12541
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251-67. doi: 10.1016/S1474-4422(18)30024-3
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