Beckwith Wiedemann syndrome (BWS) is a rare overgrowth disorder characterised by macroglossia, exomphalos, lateralised overgrowth, organomegaly, hyperinsulinism, and an increased risk of embryonic tumor during early life. In about 80% of BWS cases, molecular defects are identified at the imprinted 11p15.5 region which contains the IGF2 and the CDKN1C genes (most patients show methylation defects at either imprinting control region IC1 or IC2, or paternal uniparental isodisomy). Previously, many clinical scoring systems have been proposed to delineate BWS with variable sensitivity or specificity. Regarding clinical management, especially regarding tumor screening, no consensual approaches have hitherto been determined.
Aim: to establish recommendations regarding clinical and molecular diagnosis of BWS, and clinical management of patients with BWS.
Method: Based on a PubMed search, a comprehensive literature review was performed by a group of international experts to establish a draft consensus statement. A 3-day face-to-face meeting involving 35 participants took place in March 2017 to discuss, formulate and vote on 72 consensus recommendations.
Results: A new scoring system based on clinical symptoms (including cardinal and suggestive features) has been established to 1) indicate molecular testing and 2) define patients with a clinical diagnosis of BWS. The experts introduced the notion of Beckwith Wiedemann spectrum (BWSp) which includes patients with a molecular defect at 11p15.5 (irrespective of the clinical presentation) and those with a clinical diagnosis of BWS (irrespective of the results of the molecular investigations). Consensus recommendations are applicable to all BWSp patients. A diagnostic tree has been established to guide molecular testing in case of suspicion of BWSp, with first-line diagnosis based on methylation studies of the 11p15.5 imprinted region. Regarding clinical management, recommendations include those for growth, lateralised overgrowth, macroglossia, exomphalos, hypoglycaemia and hyperinsulinism, cardiac, renal and neurological complications. Regarding tumor screening, the experts agreed about a surveillance program stratified by the molecular subtype, with no tumor screening recommended for patients with BWSp due to an IC2 hypomethylation because of their lower tumor risk, and an abdominal ultrasound scan every 3 months until the age of 7 years for all other BWSp patients, including patients with a clinical diagnosis of BWS and no molecular defect.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology