Rhabdomyosarcoma Associated with Core Myopathy/Malignant Hyperthermia: Combined Effect of Germline Variants in RYR1 and ASPSCR1 May Play a Role

Genes (Basel). 2023 Jun 27;14(7):1360. doi: 10.3390/genes14071360.

Abstract

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants.

Keywords: ASPSCR1 protein; central core disease; malignant hyperthermia; rhabdomyosarcoma; ryanodine receptor.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Germ Cells / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Malignant Hyperthermia* / genetics
  • Muscular Diseases* / genetics
  • Rhabdomyosarcoma* / genetics
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Transcription Factors

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Transcription Factors
  • ASPSCR1 protein, human
  • Intracellular Signaling Peptides and Proteins

Grants and funding

This research was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 for manuscript preparation and by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the IVCT and genetic study. Molecular studies were supported by FAPESP-CEPID, grant no. 2013/08028-1.