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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Case report

Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

Authors: Claudia Santoro, Andrea Apicella, Fiorina Casale, Angela La Manna, Martina Di Martino, Daniela Di Pinto, Cristiana Indolfi, Silverio Perrotta

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases.

Case presentation

Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child’s kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease.

Conclusion

The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15–20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.
Literature
1.
Mehta GD, Kumar R, Srivastava S, Ghosh SK. Cohesin: functions beyond sister chromatid cohesion. FEBS Lett. 2013;587:2299–312.CrossRefPubMed
2.
Jackson L, Kline AD, Barr MA, de Koch S. Lange syndrome: a clinical review of 310 individuals. Am J Med Genet. 1993;47:940–6.CrossRefPubMed
3.
Bork G, Redon R, Sanlaville D, Rio M, Pireur M, Lyonnet S, et al. NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome. J Med Genet. 2004;41, e128.CrossRef
4.
Bhuiyan ZA, Klein M, Hammond P, van Haeringen A, Mannens MM, Van Berckelaer-Onnes I, Hennekam RC. Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience. J Med Genet. 2006;43:568–75.CrossRefPubMed
5.
Yan J, Saifi GM, Wierzba TH, Withers M, Bien-Willner GA, Limon J, et al. Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome. Am J Med Genet A. 2006;140:1531–41.CrossRefPubMed
6.
Selicorni A, Russo S, Gervasini C, Castronovo P, Milani D, Cavalleri F, et al. Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation. Clin Genet. 2007;72:98–108.CrossRefPubMed
7.
Musio A, Selicorni A, Focarelli ML, Gervasini C, Milani D, Russo S, et al. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat Genet. 2006;38:528–30.CrossRefPubMed
8.
Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. 2007;80:485–94.CrossRefPubMedPubMedCentral
9.
Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, et al. RAD21 mutations cause a humancohesinopathy. Am J Hum Genet b. 2012;90:1014–27.CrossRef
10.
Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylationcycle. Nature. 2012;489:313–7.CrossRefPubMedPubMedCentral
11.
Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. Mutation Spectrum and Genotype–Phenotype Correlationin Cornelia de Lange Syndrome. Hum Mutat. 2013;34:1589–96.CrossRefPubMed
12.
Gervasini C, Russo S, Cereda A, Parenti I, Masciadri M, Azzollini J, et al. Am J Med Genet A. 2013;161A:2909–19.CrossRefPubMed
13.
Gillis LA, McCallum J, Kaur M, DeScipio C, Yaeger D, Mariani A, et al. NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations. Am J Hum Genet. 2004;75:610–23.CrossRefPubMedPubMedCentral
14.
Selicorni A, Sforzini C, Milani D, Cagnoli G, Fossali E, Bianchetti MG. Anomalies of the kidney and urinary tract are common in de Lange syndrome. Am J Med Genet A. 2005;132A:395–7.CrossRefPubMed
15.
Cohen Jr M. The child with multiple defects. New York: Raven; 1982. p. 189.
16.
Charles AK, Porter HJ, Sams V, Lunt P. Nephrogenic rests and renal abnormalities in Brachmann-de Lange syndrome. Pediatr Pathol Lab Med. 1997;17:209–19.PubMed
17.
Maruiwa M, Nakamura Y, Motomura K, Murakami T, Kojiro M, Kato M, et al. Cornelia de Lange syndrome associated with Wilms' tumour and infantile haemangioendothelioma of the liver: report of two autopsy cases. Virchows Arch A Pathol Anat Histopathol. 1988;413:463–8.CrossRefPubMed
18.
Kline AD, Barr M, Jackson LG. Growth manifestations in the Brachmann-de Lange syndrome. Am J Med Genet. 1993;47:1042–9.CrossRefPubMed
19.
Kline AD, Calof AL, Schaaf CA, Krantz ID, Jyonouchi S, Yokomori K, et al. Cornelia de Lange syndrome: further delineation of phenotype, cohesin biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts. Am J Med Genet A. 2014;164:1384–93.CrossRef
20.
Schrier SA, Sherer I, Deardorff MA, Clark D, Audette L, Gillis L, et al. Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am J Med Genet A. 2011;155A:3007–24.CrossRefPubMed
21.
Sugita K, Izumi T, Yamaguchi K, Fukuyama Y, Sato A, Kajita A. Cornelia de Lange syndrome associated with a suprasellar germinoma. Brain Dev. 1986;8:541–6.CrossRefPubMed
22.
Chico-Ponce de León F, Gordillo-Domínguez LF, González-Carranza V, Torres-García S, García-Delgado C, Sánchez-Boiso A, et al. Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study. Childs Nerv Syst. 2015;31:141–6.CrossRef
23.
DuVall GA, Walden DT. Adenocarcinoma of the esophagus complicating Cornelia de Lange syndrome. J Clin Gastroenterol. 1996;22:131–3.CrossRefPubMed
24.
Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E. Malignant renal tumours incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42:2103–14.CrossRefPubMed
25.
Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet. 2006;43:705–15.CrossRefPubMedPubMedCentral
26.
Dumoucel S, Gauthier-Villars M, Stoppa-Lyonnet D, Parisot P, Brisse H, Philippe-Chomette P, et al. Malformations, genetic abnormalities, and Wilms tumor. Pediatr Blood Cancer. 2014;61:140–4.CrossRefPubMed
27.
Perotti D, Hohenstein P, Bongarzone I, Maschietto M, Weeks M, Radice P, et al. Is Wilms tumor a candidate neoplasia for treatment with WNT/β-catenin pathway modulators? A report from the renal tumors biology-driven drug development workshop. Mol Cancer Ther. 2013;12:2619–27.CrossRefPubMed
28.
Fukuzawa R, Anaka MR, Heathcott RW, McNoe LA, Morison IM, Perlman EJ, et al. Wilms tumour histology is determined by distinct types of precursor lesions and not epigenetic changes. J Pathol. 2008;215:377–87.CrossRefPubMed
29.
Koesters R, Ridder R, Kopp-Schneider A, Betts D, Adams V, Niggli F, et al. Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms’ tumors. Cancer Res. 1999;59:3880–2.PubMed
30.
Li CM, Kim CE, Margolin AA, Guo M, Zhu J, Mason JM, Hensle TW, et al. CTNNB1 mutations and overexpression of Wnt/beta-catenin target genes in WT1-mutant Wilms’ tumors. Am J Pathol. 2004;165:1943–53.CrossRefPubMedPubMedCentral
31.
Maiti S, Alam R, Amos CI, Huff V. Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res. 2000;60:6288–92.PubMed
32.
Fukuzawa R, Heathcott RW, Sano M, Morison IM, Yun K, Reeve AE. Myogenesis in Wilms’ tumors is associated with mutations of the WT1 gene and activation of Bcl-2 and the Wnt signaling pathway. Pediatr Dev Pathol. 2004;7:125–37.CrossRefPubMed
33.
Pistocchi A, Fazio G, Cereda A, Ferrari L, Bettini LR, Messina G, et al. Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts. Cell Death Dis. 2013;4, e866.CrossRefPubMedPubMedCentral
34.
Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998;79:268–73.CrossRefPubMed
35.
Beckwith JB. Precursor lesions of Wilms tumor: clinical and biological implications. Med Pediatr Oncol. 1993;21:158–68.CrossRefPubMed
36.
Metadata
Title
Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report
Authors
Claudia Santoro
Andrea Apicella
Fiorina Casale
Angela La Manna
Martina Di Martino
Daniela Di Pinto
Cristiana Indolfi
Silverio Perrotta
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2402-2

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