PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma in Schuurs-Hoeijmakers syndrome

J Hum Genet. 2022 Jan;67(1):51-54. doi: 10.1038/s10038-021-00965-3. Epub 2021 Aug 2.


PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma (ARMS) developed in a patient presenting with intellectual disability and dysmorphic facial features. Whole exome sequencing analysis of a germline sample identified a PACS1 c.607 C>T de novo variant and the patient was diagnosed with Schuurs-Hoeijmakers syndrome (SHS). SHS is a rare disease characterized by intellectual disability and dysmorphic facial features, among various physical abnormalities, due to PACS1 c.607 C>T de novo variant. Due to the rarity of the SHS, diagnosis based on phenotypic information is difficult. To date, there have been no previous reports describing malignancy associated with SHS. Comprehensive somatic mutation analysis revealed a unique pattern of genetic alterations in the PAX3/7-FOXO1 fusion-negative ARMS tumor, including mutations in the oncogene, HRAS; MYOD1, a molecule essential for muscle differentiation; and KMT2C and TET1, genes encoding factors involved in epigenetic regulation. Although the role of PACS1 in tumorigenesis is unclear, it is reported to function in apoptosis regulation. Our case suggests that PACS1 could have a novel role in oncogenesis.

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Alleles
  • Forkhead Box Protein O1 / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Oncogene Proteins, Fusion / genetics
  • PAX3 Transcription Factor / genetics
  • Phenotype
  • Rhabdomyosarcoma, Alveolar / diagnosis*
  • Rhabdomyosarcoma, Alveolar / etiology*
  • Syndrome


  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Oncogene Proteins, Fusion
  • PAX3 Transcription Factor
  • PAX3 protein, human