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

Journal of Human Genetics volume 67, pages 51–54 (2022)Cite this article

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Abstract

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.

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Fig. 1: A patient with Schuurs-Hoeijmakers syndrome and PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma.

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Acknowledgements

We thank the affected individuals and their families for participating in this study. This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (3905-A02) and Japan agency for medical research and development (AMED) (grant number 19ck0106467).

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Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Teppei Ohkawa, Akira Nishimura, Yuki Aoki-Nogami, Kenichi Kashimada, Tomohiro Morio, Shuki Mizutani & Masatoshi Takagi

  2. Department of Pediatrics, Chiba Kaihinn Municipal Hospital, Chiba, Japan

    Teppei Ohkawa

  3. Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan

    Kenjiro Kosaki

  4. Department of Pediatric Oncology, National Cancer Center, Tokyo, Japan

    Yuki Aoki-Nogami

  5. Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Daisuke Tomizawa

  6. Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Motohiro Kato

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  1. Teppei Ohkawa
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Correspondence to Masatoshi Takagi.

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Ohkawa, T., Nishimura, A., Kosaki, K. et al. PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma in Schuurs-Hoeijmakers syndrome. J Hum Genet 67, 51–54 (2022). https://doi.org/10.1038/s10038-021-00965-3

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