Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement

Open Access

Abstract

Beckwith–Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith–Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways. ; This Consensus Statement was organized by the European Network of Human Congenital Imprinting Disorders (EUCID.net) with financial support from European Cooperation in Science and Technology (COST; BM1208). Newlife the Charity for Disabled Children, the European Society of Pediatric Endocrinology (ESPE) and the Société Française de lutte contre les Cancers et leucémies de l'enfant et de l'adolescent (SFCE) provided funding for the consensus meeting. The European Society of Pediatric Nephrology (ESPN) provided support for the meeting. Individual authors would like to thank the following funders for research support: Alex's Lemonade Stand Foundation (J.M.K.); Bundesministerium für Bildung und Forschung (BMBF) (number 01GM1513C) (D.P.); Child Growth Foundation (K.T.-B.); European Union FP7 Innovative Training Network (ITN) Ingenium N. 290123 (Y.LeB., A.R., I.N., E.R.M.); FIS (grant PI15/01481) (P.L., J.T.); Fondation de Recherche Médicale (Y.LeB.); Margaret Q. Landenberger Foundation (J.M.K.); MIUR PRIN 2015 JHLY35 (A.R., G.B.F., S.Ru.); MOH Grants to Istituto Auxologico Italiano (grant: RC 08C502_2015) (S.Ru.); US National Institutes of Health (grant K08CA193915) (J.M.K.); UK National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration (A.C.F.); St. Baldrick's Scholar Award (J.M.K.); The Estonian Research Council (grant PUT355) (K.O.); Université P et M Curie, Institut National de la Santé Et de la Recherche Médicale (Y.L.B.); Telethon-Italia GGP15131 and AIRC IG18671 (A.R.); Wellcome Trust (M.D.K.); European Research Council (E.R.M.); and NIHR Senior Investigator Award (E.R.M.). The University of Cambridge has received salary support in respect of E.R.M. from the National Health Service (NHS) in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or UK Department of Health. No funding was received from pharmaceutical companies.