eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Beckwith-Wiedemann Syndrome: Differential Diagnoses & Workup

Author: Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Contributor Information and Disclosures

Updated: May 21, 2009

Differential Diagnoses

Fluid, Electrolyte, and Nutrition Management of the Newborn
Obesity
Glycogen-Storage Disease Type 0
Omphalocele and Gastroschisis
Glycogen-Storage Disease Type I
Persistent Hyperinsulinemic Hypoglycemia of Infancy
Hyperinsulinemia
Splenomegaly
Hyperpituitarism
Hypoglycemia

Other Problems to Be Considered

Several fetal overgrowth syndromes resemble Beckwith-Wiedemann syndrome (BWS). Some differential features are listed in Special Concerns, and the bibliography lists comprehensive monographs of these disorders. Simpson-Golabi-Behmel syndrome has been associated with deficient glypican-3, a glycosaminoglycan of the basement membrane, which binds IGF-2. Defects of this glycoprotein may result in increased tissue levels of free insulin-like growth factors, thus stimulating overgrowth.

Other causes of hypoglycemia to consider include the several genetic forms of congenital hyperinsulinism (congenital focal, diffuse sulfonylurea receptor type 1 mutations, diffuse Kir6.2 mutations, and diffuse glutamate dehydrogenase mutations), tumor-associated IGF-2 overproduction, inborn disorders of ketogenesis, and inborn errors of ketone utilization (beta-ketothiolase deficiency or succinyl CoA-transferase deficiency).

Workup

Laboratory Studies

The following studies may be indicated in patients with suspected Beckwith-Wiedemann syndrome (BWS):

  • Proper documentation of hypoglycemia (blood glucose <60 mg/dL) requires proper sample collection and processing. Guidelines for the monitoring and treatment of hypoglycemia have been established.3,4
    • Ideally, blood samples for glucose assessment should be processed immediately after collection. Cells in the blood sample continue to metabolize glucose, even at cold temperatures, leading to falsely low glucose values and falsely high lactate values. Collecting the blood in a sodium fluoride-lined tube (gray top tube) inhibits glycolysis, reducing the likelihood of falsely low values.
    • Measurements made with portable glucometers are useful for screening but not for diagnosis of hypoglycemia. Portable glucometers are widely available and relatively inexpensive, which are their primary advantages in the outpatient management of diabetes mellitus. These devices, however, were not designed for accuracy because distinguishing between blood glucose values of 200 and 220 mg/dL, for example, is less important than making the device convenient and affordable. When compared with central laboratory assays, these glucometers display as high as 20% inaccuracy at the lower ranges. For diagnostic purposes (during fasting studies and in other hospital settings), blood glucose should be measured in the central hospital laboratory, preferably by the well-established glucose oxidase method. Portable glucometers remain useful for monitoring blood sugar on an outpatient basis, but persistent low values should prompt consultation with the physician.
    • At the time of hypoglycemia, obtain plasma ketones (acetoacetate and b-hydroxybutyrate), plasma free fatty acid, serum insulin, and serum IGF levels (IGF-1 and IGF-2 by radioimmunoassay; large molecular weight forms of IGF-2 can be detected by Western ligand blot).
    • If intravenous or intramuscular administration of 1 mg glucagon at the time of hypoglycemia results in a rise of blood glucose of at least 30 mg/dL above baseline, the test is consistent with inappropriately conserved glycogen stores as observed in hyperinsulinism or panhypopituitarism.
  • Patients with Beckwith-Wiedemann syndrome should be screened for hypercalciuria. A single random, nonfasting urine sample obtained at each health maintenance visit is adequate for this purpose.

Imaging Studies

  • Longitudinal abdominal ultrasonography has been suggested to screen for embryonal tumors, although it should be performed concomitantly with training parents to examine their child's abdomen. Most authorities recommend at least biannual abdominal ultrasonographic examinations; however, in 1983, Professor Wiedemann recommended that children with Beckwith-Wiedemann syndrome undergo renal sonography at 3-month intervals through the third year of life and at 6-month intervals thereafter. Recent reports of rapidly presenting Wilms tumors in patients with Beckwith-Wiedemann syndrome continue to support this traditional guideline.
  • Chest radiography may exclude rare neural crest tumors such as thoracic neuroblastoma.

Procedures

  • Perform an inpatient fasting study to identify the cause of hypoglycemia. Acute insulin response testing (currently available only as research protocol at the Children's Hospital of Philadelphia) may be performed to differentiate from known forms of congenital hyperinsulinism.

More on Beckwith-Wiedemann Syndrome

Overview: Beckwith-Wiedemann Syndrome
Differential Diagnoses & Workup: Beckwith-Wiedemann Syndrome
Treatment & Medication: Beckwith-Wiedemann Syndrome
Follow-up: Beckwith-Wiedemann Syndrome
Multimedia: Beckwith-Wiedemann Syndrome
References
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References

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Further Reading

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Keywords

Beckwith-Wiedemann syndrome, BWS, exomphalos, macroglossia, congenital exomphalos, congenital macroglossia, gigantism syndrome, EMG syndrome, Wilms tumor, omphalocele with macroglossia, hepatoblastoma, organomegaly, hypoglycemia, anterior abdominal wall defects, helical indentations, organ overgrowth, nephromegaly, hemihypertrophy, genitourinary abnormalities, embryonal tumors, adrenocortical neoplasias, treatment, diagnosis

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Contributor Information and Disclosures

Author

Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
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, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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 Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Lawson-Wilkins Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and 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, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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