Beckwith‐Wiedemann syndrome in adults: Observations from one family and recommendations for care

Abstract

Literature review and clinical findings in four affected adult males from one family suggest that there are serious and currently ill-defined health risks in adults with Beckwith-Wiedemann syndrome (BWS). These may include male subfertility, vascular anomalies, renal abnormalities, hearing loss and, possibly, an increased risk for adult-onset malignancy. Given present knowledge, recommendations in caring for adults with this disorder remain tentative but likely should include counseling for possible infertility in males, screening echocardiography, renal sonogram and renal function testing, and counseling about possible increased risk for adult onset malignancy.

Beckwith-Wiedemann Syndrome: Growth Pattern and Tumor Risk according to Molecular Mechanism, and Guidelines for Tumor Surveillance

“…However, data for adult height are inconclusive because of lack of information due to the discontinuation of follow-up after the usual period of surveillance for the occurrence of tumors. Several studies have reported patients in small cohorts to have a final height in the normal range [8,9,10,11], whereas others have reported adult heights exceeding +2 SDS [12,13,14,15,16,17,18] (table 1). …”

Beckwith–Wiedemann and IMAGe syndromes: two very different diseases caused by mutations on the same gene

“…This occurrence is probably underestimated as milder phenotypes may not be ascertained 12. Males and females are affected equally, with the exception of monozygotic twins who show a female predominance 13.…”

“…Focusing on CDKN1C mutations, subfertility in males, predisposition to aneurysmal arterial dilation, renal abnormalities, hearing loss, and, perhaps, increased risk for adult-onset malignancy are known 12. Romanelli et al29 reviewed the CDKN1C -related phenotypic features in BWS patients, and suggested that these patients show a peculiar pattern of clinical malformations in comparison with those with other molecular defects, and therefore the peculiar clinical presentation of the patients can be useful to address the molecular analysis.…”

A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

“…Patients with Weaver syndrome (OMIM 277590), also known as EZH2 -related overgrowth, have some clinical overlap with features resembling Sotos syndrome includ- [Greer et al, 2008]. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and in clinically diagnosed patients in whom no molecular defect was detectable (6.7%) [Maas et al, 2016].…”

“…This detects methylation abnormalities such as: (1) loss of methylation of the imprinting center 2 on the maternal chromosome, (2) gain of methylation of imprinting center 1 on the maternal chromosome, and (3) paternal uniparental disomy of 11p15.5. In addition, Sanger or next generation sequencing methods are needed to detect CDKN1C mutations that are present in only 5% of sporadic BWS cases but in 40% of patients with a family history of BWS Greer et al, 2008;Choufani et al, 2010].…”