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Beckwith-Wiedemann Syndrome: Historical, Clinicopathological, and Etiopathogenetic Perspectives

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Pediatric and Developmental Pathology

Abstract

Macroglossia, prenatal or postnatal overgrowth, and abdominal wall defects (omphalocele, umbilical hernia, or diastasis recti) permit early recognition of Beckwith-Wiedemann syndrome. Complications include neonatal hypoglycemia and an increased risk for Wilms tumor, adrenal cortical carcinoma, hepatoblastoma, rhabdomyosarcoma, and neuroblastoma, among others. Perinatal mortality can result from complications of prematurity, pronounced macroglossia, and rarely cardiomyopathy. The molecular basis of Beckwith-Wiedemann syndrome is complex, involving deregulation of imprinted genes found in 2 domains within the 11p15 region: telomeric Domain 1 (IGF2 and H19) and centromeric Domain 2 (KCNQ1, KCNQ1OT1, and CDKN1C). Topics discussed in this article are organized as a series of perspectives: general, historical, epidemiologic, clinical, pathologic, genetic/molecular, diagnostic, and differential diagnostic.

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Notes

  1. In contrast, postaxial polydactyly of the hands is very common in Simpson-Golabi-Behmel syndrome [7].(3 cases).

  2. Two other genes PHLDA2 and SLC22A18 in domain 2, which show preferential maternal expression, may have negative growth regulatory functions. However, to date, neither gene has been directly implicated in Beckwith-Wiedemann syndrome [30].

  3. ‡In contrast, study of hematopoietic cells for affected and unaffected twins shows similar imprinting alterations because sharing of hematopoietic stem cells via placental vascular anastomoses is a common feature of monozygotic twinning.

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    M. Michael Cohen Jr

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Cohen, M.M. Beckwith-Wiedemann Syndrome: Historical, Clinicopathological, and Etiopathogenetic Perspectives. Pediatr Dev Pathol 8, 287–304 (2005). https://doi.org/10.1007/s10024-005-1154-9

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