Characterization of the Beckwith‐Wiedemann spectrum: Diagnosis and management

Abstract

Beckwith‐Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, patients can present with a variety of clinical features, leading to the newly defined Beckwith‐Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.

Need for a precise molecular diagnosis in Beckwith-Wiedemann and Silver-Russell syndrome: what has to be considered and why it is important

“…In BWS, the frequencies of the molecular subgroups corresponded to that of previous studies (e.g. [1,21,22]), with IC2 LOM as the most frequent findings, followed by upd(11)pat. In 9.5% of cases diagnosed as upd(11)pat (4 out of 42), a mosaic paternal uniparental diploidy (also known as genome-wide uniparental disomy) could be identified.…”

Current Status of Nursing Research on Beckwith Wiedemann Syndrome Based on Co-word Analysis

“…The expression study found that the 11p15.5 region of BWS is an imprinted gene cluster, its p57 mutation, IGF2/H19 transcriptional abnormality chromosomal translocation (inversion) and methylation of CpG island upstream of LITI gene may be the cause of BWS. These genes have a tendency to share regulatory mechanisms, so the onset of BWS may be the result of multiple genes, but the exact pathogenesis remains to be further studied [16].…”

Diagnosis and Management of Beckwith-Wiedemann Syndrome

“…First-line diagnostic testing is usually performed on DNA derived from blood-leukocytes (2). Other samples such as buccal swabs, skin fibroblasts, or cells of mesenchymal origins including surgical resections and/or excisions of hyperplastic tissues, can improve the detection of mosaicism (3,35,36). A negative result does not exclude a diagnosis of BWS and may be the result of low-level mosaicism that is below the level of detection, a rare balanced chromosomal rearrangement, or another currently unrecognized cause (2).…”

“…In up to 20% of patients with a BWS phenotype, a molecular diagnosis remains unknown (1). This may be due to tissue mosaicism, as testing multiple tissues improves diagnostic yield (3). Patients without a confirmed molecular diagnosis should be evaluated for clinical features suggestive of different diagnosis and appropriate additional testing should be considered (2).…”

“…These features include macroglossia, abdominal wall defects, lateralized overgrowth, enlarged abdominal organs, and an increased risk for developing embryonal tumors during early childhood (2). BWS is now considered a spectrum (BWSp) ranging from classic BWS to isolated lateralized overgrowth (2,3). BWS has an estimated prevalence of 1 affected child in 10,340 live births (4), with an increased risk associated with assisted reproductive technologies (ART) of around 1 in 1,100 (5)(6)(7).…”