Short report Acute lymphocytic leukaemia in a child with BeckwitheWiedemann syndrome harbouring a CDKN1C mutation C. Abadie a, * , F. Bernard b , I. Netchine c, d, e , D. Sanlaville f, g , A. Roque h , S. Rossignol c, d, e , I. Coupier a, i a Department of Medical Genetics, Oncogenetics, Montpellier University Hospital, France b Department of Anaesthesiology-Reanimation, Montpellier University Hospital, France c Department of Paediatric Endocrinology, APHP, Armand Trousseau Hospital, Paris, France d Research Center Inserm U 983, Paris, France e UPMC, Université Pierre et Marie Curie, Paris, France f HCL, Department of Cytogenetics, Bron, France g EA 4171, UCBL1, Lyon, France h Psychotherapy, Saint Jean de Védas, France i Department of Oncogenetics, CRLCC Val d’Aurelle, Montpellier, France article info Article history: Received 1 June 2010 Accepted 24 August 2010 Available online 6 September 2010 Keywords: BeckwitheWiedemann syndrome CDKN1C T-type acute lymphoblastic leukaemia abstract BeckwitheWiedemann syndrome (BWS) is a rare overgrowth syndrome associated with an increased risk in childhood tumours. The phenotypic variability in BWS reflects its molecular heterogeneity. This syndrome is a multigenic disorder caused by dysregulation of imprinted growth regulatory genes in the 11p15.5 region. The most commonly reported tumours in this syndrome are tumours of embryologic origin such as Wilms tumours, hepatoblastomas, neuroblastomas, rhabdomyosarcomas and adrenocor- tical carcinomas. We report the case of a 10-year-old patient diagnosed with BWS, harbouring a CDKN1C (p57 KIP2 ) mutation, who developed a T-type acute lymphoblastic leukaemia. To our knowledge it is the first report of an acute lymphoblastic leukaemia of T-type in a child with BWS. We discuss the possibility of a link between BWS and leukaemia via one of the few known negative regulator of hematopoiesis, the transforming growth factor beta pathway, depending upon the up- regulation of CDKN1C. Ó 2010 Elsevier Masson SAS. All rights reserved. 1. Introduction BeckwitheWiedemann syndrome is a rare overgrowth syndrome associated with cancer predisposition. BWS is usually recognisable at birth based on clinical features that may include macrosomia, macroglossia, abdominal wall defects, visceromegaly (including liver, kidneys and spleen). Hemihyperplasia, neonatal hypoglycaemia, ear anomalies and facial nevus flammeus can complete the phenotype. Between 2% and 30% (depending of the molecular anomaly identified and if it involves or not the IGF2 gene) of BWS patients develop cancer [3,9]. In the first five years of life, the most commonly reported tumours are of embryologic origin such as nephroblastoma, hepatoblastoma, neuroblastoma, rhabdomyosarcoma and adrenocortical carcinomas. All types of tumours in BWS were reviewed by Lapunzina [8] and it confirmed the preponderance of nephroblastoma (43%) in the syndrome. Tumour risk in BWS depends upon clinical and molecular subtypes [2,9]. Genetic abnormalities are found in around 30% of the BWS patients with identified molecular anomalies. They include : (i) maternal translocations or paternal duplications of the 11p15 region (1e2%), (ii) somatic mosaicism for paternal uniparental disomy (20%), and (iii) germline null mutations in the maternal allele of an inhibitor of the cell cycle, CDKN1C (5%). Most BWS patients with identified molecular anomalies (70%) exhibit an epigenetic defect. Ten percent of BWS patients display an imprinting defect within the telomeric domain. Finally, 50e60% of BWS cases exhibit a loss of methylation (LOM) at the maternal imprinting center region 2 (ICR2) [4]. The ICR2 LOM results in activation of the normally silent maternal allele of KCNQ1OT1 and in CDKN1C silencing (Fig. 1). Recently, many studies have shown a correlation between the tumour frequency and the molecular * Corresponding author. Department of Medical Genetics, Oncogenetics, Mont- pellier University Hospital, 371 av. Du Doyen G. Giraud, 34275 Montpellier Cedex5, France. Tel.: þ33 4 67 33 07 21; fax: þ33 4 67 33 66 72. E-mail address: abadie_caro@yahoo.fr (C. Abadie). Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg 1769-7212/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmg.2010.08.006 European Journal of Medical Genetics 53 (2010) 400e403