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Beckwith-Wiedemann Syndrome

  • Author: Sunil Sinha, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Nov 17, 2014
 

Background

In 1964, Hans-Rudolf Wiedemann reported a familial form of omphalocele with macroglossia in Germany. In 1969, J. Bruce Beckwith of Loma Linda University, California, described a similar series of patients. Originally, Professor Wiedemann coined the term EMG syndrome to describe the combination of congenital exomphalos, macroglossia, and gigantism. Over time, this constellation was renamed Beckwith-Wiedemann syndrome (BWS). Beckwith-Wiedemann syndrome is the most common overgrowth syndrome in infancy.[1]

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Pathophysiology

Although the underlying causes of Beckwith-Wiedemann syndrome remain unclear, approximately 80% of patients demonstrate genotypic abnormalities of the distal region of chromosome arm 11p. The Beckwith-Wiedemann syndrome region of 11p was the first identified example of imprinting in mammals (ie, the process whereby the 2 alleles of a gene are expressed differentially). Authors have most often used the term imprinted to refer to the expressed allele. For example, the maternal allele of band 11p15.5 is normally expressed, or imprinted. Some authors, however, designate the silent allele as the imprinted gene.

When reviewing the literature, a reader must bear in mind this inconsistent and confusing nomenclature. Imprinting has been associated with structural modifications of DNA near the gene, such as methylation or lack of acetylation. Several 11p genes are imprinted, including p57 (a cation-independent cyclase), IGF-2 (the gene for insulinlike growth factor-2 [IGF-2]), the gene for insulin, and H19.[2]

H19 is particularly interesting because this gene is transcribed but not translated. H19 messenger RNA (mRNA) appears critical for proper imprinting of the nearby insulin and IGF-2 genes because deletion of H19 or transposition from its usual position relative to IGF-2 disrupts normal imprinting. Evidence reveals that H19 mRNA binds IGF-2 mRNA binding protein, which may be one mechanism by which it affects IGF-2 production.

The mode of inheritance in Beckwith-Wiedemann syndrome is complex. Reported patterns include autosomal dominance with variable expressivity, contiguous gene duplication at band 11p15.5, microdeletions, and aberrant genomic imprinting (resulting from a defective or absent copy of the maternally derived allele). Although not universal, the overgrowth associated with Beckwith-Wiedemann syndrome appears to be most often the result of increased IGF-2 action within prenatal and postnatal tissues.

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Epidemiology

Frequency

United States

US frequency is estimated at 1 in 15,000 live births.

International

Worldwide frequency is estimated at 1 in 13,700 live births in other developed countries. Incidence is also higher in infants produced with in vitro fertilization.

Mortality/Morbidity

Mental retardation is common. Strict maintenance of euglycemia reduces the risk of nervous tissue damage.

Race

No race predilection is observed.

Sex

No sex predilection is noted.

Age

Beckwith-Wiedemann syndrome is a congenital disorder. Wilms tumor is the most common cancer in children with Beckwith-Wiedemann syndrome, occurring in about 5-7% of all children with Beckwith-Wiedemann syndrome. Most children develop Wilms tumor before age 4 years; however, children with Beckwith-Wiedemann syndrome can develop Wilms tumor when they are as old as 7-8 years. By age 8 years, 95% of all Wilms tumor cases have been diagnosed.[3]

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Contributor Information and Disclosures
Author

Sunil Sinha, MD Assistant Professor, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Sunil Sinha, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

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Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
 
 
 
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