Beckwith-Wiedemann Syndrome Differential Diagnoses

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Sections Beckwith-Wiedemann Syndrome
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
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Medication
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References

DDx

Diagnostic Considerations

Several fetal overgrowth syndromes resemble Beckwith-Wiedemann syndrome (BWS). 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).

Refer the child to an early childhood intervention program to reduce the risk of permanent developmental delays. Speech and occupational therapies are particularly important in light of macroglossia.

Commercial assays cannot detect all forms of IGF and IGF-binding proteins. The authors are happy to discuss and provide their IGF-related assays with clinicians caring for patients with BWS.

BWS has features of fetal overgrowth, organomegaly, and risk of embryonal tumors, which often overlap other conditions; however, BWS can often be differentiated with its features of exomphalos and posterior helical pits.

Wilms tumor, aniridia, genitourinary defects, and mental retardation (WAGR) syndrome carries a more than 50% prevalence of Wilms tumor (compared with 5% in patients with BWS) and is differentiated from BWS because it is associated with 11p13 deletion or mutation of the WT1 tumor suppressor gene, aniridia, and genitourinary defects.
11p trisomy is similar to BWS because of its associated feature of fetal overgrowth but is differentiated because of associated features of a high forehead with frontal upsweep of hair, beaked nose with wide central nasal bridge, chubby cheeks, and severe mental retardation.
Simpson-Golabi-Behmel syndrome is similar to BWS because of its prenatal and postnatal overgrowth, neonatal hypoglycemia, risk of embryonal tumors, and splenomegaly. Differentiating features include syndactyly, 13 ribs, slight obesity, cataract, retinal detachment, pectus excavatum, intestinal malrotation, Meckel diverticulum, hypospadias, advanced bone age, X-linked inheritance, high early perinatal and infant mortality, and cryptorchidism.
Sotos syndrome (cerebral gigantism) is similar to BWS because of its autosomal dominance and macrocephaly but is differentiated by advanced bone age, neonatal hypotonia, normal growth hormone production, rapid early growth, hypothyroidism or hyperthyroidism, arm span greater than height, dolichocephaly, alveolar ridge exostoses, and generalized neonatal edema.
Weaver syndrome is similar to BWS because of its features of accelerated growth, advanced bone age, and macrocephaly but is differentiated by camptodactyly, serrated gums, clinodactyly of fifth digit, and cryptorchidism.
Klippel-Trenaunay-Weber syndrome is similar to BWS because of its association with mental retardation and seizure but is differentiated by glaucoma and Kasabach-Merritt syndrome. The combination of macrosomia, obesity, macrocephaly, and ocular abnormalities (MOMO) may have overlapping features with BWS of macrosomia and macrocephaly but is differentiated by its associated morbid obesity and ocular abnormalities.

Differential Diagnoses

Workup

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Media Gallery

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

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Author

Sunil Kumar Sinha, MD

Sunil Kumar 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

Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children's Hospital

Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, 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

Sections Beckwith-Wiedemann Syndrome
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
References

Beckwith-Wiedemann Syndrome Differential Diagnoses

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