Wilms tumor in patients with osteopathia striata with cranial sclerosis

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1.

    Gripp KW. Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet. 2005;137C:72–7.

    Article  Google Scholar 

  2. 2.

    Weksberg R, Nishikawa J, Caluseriu O, Fei Y-L, Shuman C, Wei C, et al. Tumor development in the Beckwith–Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10:2989–3000.

    CAS  Article  Google Scholar 

  3. 3.

    Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD. Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet. 1986;74:143–54.

    CAS  Article  Google Scholar 

  4. 4.

    DeBaun MR, Siegel MJ, Choyke PL. Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J Pediatrics. 1998;132:401–4.

    CAS  Article  Google Scholar 

  5. 5.

    Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14:229–49.

    Article  Google Scholar 

  6. 6.

    Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes Cancer. 2008;47:461–70.

    CAS  Article  Google Scholar 

  7. 7.

    Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M. et al. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science. 2007;315:642–5.

    CAS  Article  Google Scholar 

  8. 8.

    Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, et al. Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet. 2009;41:95–100.

    CAS  Article  Google Scholar 

  9. 9.

    Perdu B, Freitas FD, Frints SG, Schouten M, Schrander-Stumpel C, Barbosa M, et al. Osteopathia striata with cranial sclerosis owing to WTX gene defect. J Bone Miner Res. 2010;25:82–90.

    CAS  Article  Google Scholar 

  10. 10.

    Fukuzawa R, Holman SK, Chow CW, Savarirayan R, Reeve AE, Robertson SP. WTX mutations can occur both early and late in the pathogenesis of Wilms tumour. J Med Genet. 2010;47:791–4.

    CAS  Article  Google Scholar 

  11. 11.

    Sperotto F, Bisogno G, Opocher E, Rossi S, Rigon C, Trevisson E, et al. Osteopathia striata with cranial sclerosis and Wilms tumor: coincidence or consequence? Clin Genet. 2017;92:674–5.

    CAS  Article  Google Scholar 

  12. 12.

    Tanneberger K, Pfister AS, Kriz V, Bryja V, Schambony A, Behrens J. Structural and functional characterization of the Wnt inhibitor APC membrane recruitment 1 (Amer1). J Biol Chem. 2011;286:19204–14.

    CAS  Article  Google Scholar 

  13. 13.

    Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C. et al. Wilms tumor suppressor WTX negatively regulates WNT/β-catenin signaling. Science. 2007;316:1043–6.

    CAS  Article  Google Scholar 

  14. 14.

    Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003;129:199–221.

    CAS  Article  Google Scholar 

  15. 15.

    Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006;127:469–80.

    CAS  Article  Google Scholar 

  16. 16.

    Berenholz L, Lippy W, Harrell M. Conductive hearing loss in osteopathia striata-cranial sclerosis. Otolaryngol Head Neck Surg. 2002;127:124–6.

    Article  Google Scholar 

  17. 17.

    Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al. (eds). SEER Cancer Statistics Review, 1975–2016 (Bethesda, MD: National Cancer Institute, 2019).

  18. 18.

    Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2010;18:8–14.

    Article  Google Scholar 

  19. 19.

    Fujita A, Ochi N, Fujimaki H, Muramatsu H, Takahashi Y, Natsume J, et al. A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. Am J Med Genet A. 2014;164:998–1002.

    CAS  Article  Google Scholar 

  20. 20.

    Özyörük D, Emir S. The management of bilateral Wilms tumor. Transl Pediatr. 2014;3:34–8.

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Fukuzawa R, Anaka MR, Weeks RJ, Morison IM, Reeve AE. Canonical WNT signalling determines lineage specificity in Wilms tumour. Oncogene. 2009;28:1063–75.

    CAS  Article  Google Scholar 

  22. 22.

    Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 1990;10:1–36.

    CAS  Article  Google Scholar 

  23. 23.

    Brodeur GM, Nichols KE, Plon SE, Schiffman JD, Malkin D. Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. Knudson Jr. Clin Cancer Res. 2017;23:e1–e5.

    Article  Google Scholar 

  24. 24.

    Metzger ML, Dome JS. Current therapy for Wilms’ tumor. Oncologist 2005;10:815–26.

    CAS  Article  Google Scholar 

  25. 25.

    Tournade MF, Com-Nougué C, de Kraker J, Ludwig R, Rey A, Burgers JMB, et al. Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms’ tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms’ Tumor Trial and Study. J Clin Oncol. 2001;19:488–500.

    CAS  Article  Google Scholar 

  26. 26.

    Craft AW. Growth rate of Wilms’ tumour. Lancet 1999;354:1127.

    CAS  Article  Google Scholar 

  27. 27.

    DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatrics. 1998;132:398–400.

    CAS  Article  Google Scholar 

  28. 28.

    Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, et al. (eds). Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995 (Bethesda, MD: National Cancer Institute, 1999).

  29. 29.

    Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21:172–81.

    CAS  Article  Google Scholar 

Download references

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).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Stephen P. Robertson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Search