Giant omphalocele and “prune belly” sequence as components of the Beckwith–Wiedemann syndrome

Abstract

We report a case of severe Beckwith-Wiedemann syndrome (BWS) in a fetus at 16 weeks of gestation. This presentation, incompatible with life, included a giant omphalocele and absence of abdominal wall musculature with extremely dilated bladder, as in the "prune belly" sequence. Adrenal cytomegaly pointed to BWS. Molecular analysis confirmed the diagnosis of BWS and showed an isolated demethylation of the KCNQ1OT1 gene. This report demonstrates that lethal fetal abdominal wall defects associated with adrenal cytomegaly are linked to epigenetic change of the 11p15 imprinted region.

Hepatoblastoma and prune belly syndrome: a potential association

“…These include proven genetic, prenatal, and perinatal factors that confer risk of HBL, as well as a variety of potential intrauterine exposures that have been described in association with HBL (Table S1). Of note, we found no evidence to support a diagnosis of BWS in these patients, despite case reports in the literature of potential overlap between PBS and BWS [17][18][19][20] and the well-accepted association of HBL with BWS [7]. While 75% of the patients in our study were born prematurely, two separate studies have found that, after adjusting for birth weight, prematurity does not confer HBL risk [21,22].…”

Unilateral agenesis of the abdominal wall musculature: An early muscle deficiency

“…PBS is known to be causally heterogeneous: most cases are sporadic (with a M/F sex ratio of 19:1), but autosomal recessive, autosomal dominant, and X-linked pedigrees have been reported [Grenet et al, 1972;Adeyokunnu and Familusi, 1982;Gaboardi et al, 1982;Darmon et al, 1992;Balaji et al, 2000;Chan and Bird, 2004;Ramasamy et al, 2005]. Epigenetic form of PBS have been reported, such as hypomethylation of KCNQ1OT1 gene in the association of prune belly and Beckwith Wiedemann syndrome [Sinico et al, 2004] or multiple loss of methylation in 6q24 (TNDM) and also at the loci of IGF2R (6q26), DIRAS3 (1p31), and PEG1 (7q32) in a monozygotic twin with prune belly and transient neonatal diabetes [Laborie et al, 2010]. Two pathogenic mechanisms have been proposed to explain PBS: a bladder distension sequence and an intrinsic abnormality in the development of the lateral plate mesoderm [Popek et al, 1991;Tan et al, 1996;Vermeij-Keers et al, 1996;Vauthay et al, 2007;Nouaili et al, 2008].…”

Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype-genotype correlations in Beckwith-Wiedemann syndrome

“…Recently, a case of giant omphalocoele and ''prune belly'' sequence in a prenatal case of BWS was investigated only for KCNQ1OT1/LIT1 promoter methylation analysis (and not H19) in fetal liver DNA showing 10% of residual methylation. 30 This finding does not exclude the presence of a somatic mosaic of UPD11 (90%) and normal (10%) cell lines, even in a pattern confined to a single organ. Investigations of UPD11 in abdominal tissues from patients with BWS with omphalocoele and negative for CDKN1C mutations might strengthen the importance of UPD11 tissue specificity in the BWS phenotype.…”