Wilms tumor in patients with osteopathia striata with cranial sclerosis

European Journal of Human Genetics (2020)Cite this article

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Abstract

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15–30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith–Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.

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Fig. 1: Clinical, radiographical and histological data from cases 2 and 3.

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Acknowledgements

We thank the individuals and their families described in this report. SPR is supported by Curekids. ET is supported by Istituto di Ricerca Pediatrica (IRP).

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Author notes

  1. These authors contributed equally: Alicia Bach, Jingyi Mi

Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St Louis, MI, USA

    Alicia Bach & Daniel N. Willis

  2. Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin, 9016, New Zealand

    Jingyi Mi, Benjamin J. Halliday & Stephen P. Robertson

  3. Monash Genetics, Monash Medical Centre, Melbourne, VIC, Australia

    Matthew Hunter

  4. Department of Paediatrics, Monash University, Melbourne, VIC, Australia

    Matthew Hunter

  5. Instituto de Genética Médica y Molecular, La Paz University Hospital, Madrid, Spain

    Sixto García-Miñaúr

  6. Department of Women’s and Children’s Health, Padova University, Padova, Italy

    Francesca Sperotto

  7. Institute of Pediatric Research Città della Speranza, Clinical Genetics and Epidemiology Laboratory, Padova University, Padova, Italy

    Eva Trevisson

  8. Clinical Genetics Unit, Department of Women’s and Children’s Health, University of Padova, Padova, Italy

    Eva Trevisson

  9. Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, 9016, New Zealand

    David Markie & Ian M. Morison

  10. Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MI, USA

    Marwan Shinawi

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  1. Alicia Bach
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Correspondence to Stephen P. Robertson.

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Bach, A., Mi, J., Hunter, M. et al. Wilms tumor in patients with osteopathia striata with cranial sclerosis. Eur J Hum Genet (2020). https://doi.org/10.1038/s41431-020-00718-4

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