Adrenal gland and paraganglia
Congenital anomalies
Beckwith-Wiedemann syndrome

Author: Brad Wasserman, M.D. (see Authors page)

Revised: 14 January 2016, last major update June 2013

Copyright: (c) 2002-2016,, Inc.

Cite this page: Beckwith-Wiedemann syndrome. website. Accessed October 23rd, 2016.
Definition / General
  • Overgrowth syndrome characterized by macrosomia, macroglossia, visceromegaly, embryonal neoplasms (mainly Wilms tumor (WT) and hepatoblastoma), omphalocele/exomphalos, neonatal hypoglycemia, ear creases, adrenocortical cytomegaly, and renal abnormalities
  • Originally called EMG, based on clinical findings of exomphalos, macroglossia, and gigantism
  • Genomic imprinting: a subset of imprinted autosomal genes are expressed from only one allele (the paternal or maternal copy)
  • Incidence of 1:13,700 births
  • Occurs in a variety of ethnic populations
  • M=F
  • Mortality rate of 20% may be an overestimate given recent improvements in recognition and treatment
  • Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or neoplasms
  • Milder phenotypes may develop tumors associated with BWS
  • Most individuals with BWS have normal chromosome studies or karyotypes
  • Children conceived by assisted reproductive technology (ART) may have an increased risk for imprinting disorders (quasi-familial) (J Med Genet 2003;40:62 and Hum Reprod 2003;18:2508 as cited in GeneReviews 2000 Mar 03 [updated 2010 Dec 14])
  • Epigenetic dysregulation of gene transcription within the BWS critical region (imprint domain) on chromosome 11p15 (sporadic):
    • Loss of methylation of IC2 on the maternal chromosome (50%)
    • Paternal uniparental disomy (UPD) of 11p15 (20%)
    • Gain of methylation of IC1 on the maternal chromosome (5%)
  • Imprinting centers (IC1 and IC2) control gene expression across large chromosomal domains
  • Imprinted genes, including growth factors and tumor suppressor genes mapping to the 11p15 region, have been implicated
  • Duplication, inversion, or translocation involving the p15.5 band of chromosome 11 are found in <1% of affected individuals (familial)
Clinical Features
  • Macrosomia (height and weight >97th percentile)
  • Macroglossia
  • Anterior linear ear lobe creases/posterior helical ear pits
  • Anterior abdominal wall defects
    • Omphalocele/exomphalos
    • Umbilical hernia
    • Diastasis recti
  • Visceromegaly involving liver, spleen, kidneys, adrenals, and pancreas
  • Renal abnormalities (nephrocalcinosis, medullary sponge kidney, cystic changes, diverticula, nephromegaly)
  • Cytomegaly of fetal adrenal cortex (adrenocortical cytomegaly)
  • Embryonal neoplasms (Wilms tumor (WT), hepatoblastoma, neuroblastoma, adrenocortical carcinoma, rhabdomyosarcoma)
    • Increased risk for neoplasia occurs in first eight years of life
  • Hemi hyperplasia (asymmetric overgrowth of one or more regions of the body)
    • May affect segmental regions of body or selected organs and tissues
  • Pregnancy-related findings include polyhydramnios and prematurity
  • For all pregnancies at increased risk for BWS, whether or not the genetic mechanism is known:
    • Maternal serum alpha-fetoprotein (AFP) concentration may be elevated at 16 weeks' gestation in presence of an omphalocele
    • Obtain ultrasound at 19-20 and 25-32 weeks gestation to assess growth parameters, detect abdominal wall defects, visceromegaly, renal anomalies, and macroglossia
  • Post-natal screening for embryonal neoplasms (Genet Med 2009;11:220 and J Pediatr 2000;137:123 as cited in GeneReviews 2000 Mar 03 [updated 2010 Dec 14]):
    • Abdominal ultrasound examination every three months until age 8 years
    • Measure serum alpha-fetoprotein (AFP) concentration every two to three months until age 4 years, for early detection of hepatoblastoma (AFP serum concentration declines in postnatal period at slower rate than in healthy children, and may be elevated in first year of life in BWS)
  • Periodic chest x-ray and urinary VMA and VHA assays to screen for neuroblastoma have not been incorporated into screening protocols because of their low yield
Radiology Images
Images hosted on other servers:

CT scan of the abdomen showing a cystic adrenal lesion on the right

Case Reports
Clinical Images
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Anterior linear crease

Posterior helical ear pits

Gross Description
  • Long umbilical cord (>70 cm attached to placenta, measured at gross bench)
  • Enlarged placenta (2x for gestational age)
  • Placental mesenchymal dysplasia (Arch Pathol Lab Med 2007;131:131)
    • Bulky placenta with a "bed of yarn" appearance to maternal surface
    • Dilated and thrombosed vessels of chorionic plate
    • Resembles partial mole
  • Enlarged adrenal glands (up to 16 g) with cerebriform and nodular surface
Gross Images
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Large lobulated adrenal glands

Placental mesenchymal dysplasia

Micro Description
  • Adrenal cytomegaly
    • Adrenal cortical cells with bizarre, enlarged polyhedral cells with granular eosinophilic cytoplasm and large, hyperchromatic nuclei with pseudoinclusions
    • Rare mitotic figures
  • Placental mesenchymal dysplasia
    • Dilated and thick-walled chorionic plate vessels with fibro-muscular hyperplasia
  • Nephrocalcinosis
    • Diffuse tubular injury with atrophy, interstitial fibrosis and abundant tubular deposition of calcium phosphate
Micro Images
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Adrenocortical cytomegaly

Placental mesenchymal dysplasia