Table 6.

Disorders with Hemihyperplasia or Lateralized Overgrowth to Consider in the Differential Diagnosis of Beckwith-Wiedemann Syndrome

Gene(s) / Genetic MechanismDisorderMOIFeatures of DiffDx Disorder
Overlapping w/BWSDistinguishing from BWS
Genetically heterogeneous 1Silver-Russell syndrome (SRS)See footnote 2.Growth asymmetry of regions of the body (e.g., ≥1 limbs)Most clinical features that are characteristic of SRS (e.g., growth failure) are not seen in BWS. In addition, SRS is not assoc w/↑ risk for embryonal tumors.
AKT1 Proteus syndrome See footnote 3.Asymmetric overgrowth, vascular malformations incl cutaneous capillary malformationsProgressive segmental or patchy overgrowth most commonly affecting skeleton, skin, adipose, & CNS; modest or no manifestations at birth; progression through childhood, causing severe overgrowth & disfigurement & range of tumors
NF1 Neurofibromatosis 1 ADAsymmetric overgrowthMultiple café au lait macules, intertriginous freckling, cutaneous neurofibromas, Lisch nodules
PIK3CA PIK3CA-related overgrowth spectrum (PROS) (incl CLOVES syndrome, MCAP syndrome, & Klippel-Trenaunay syndrome)See footnote 3.Hemihyperplasia, vascular malformationsVariable presentations; see PROS for comprehensive clinical descriptions, recommendations for testing (often requires tissues other than blood), & mgmt.
PTEN PTEN hamartoma tumor syndrome (incl Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, & PTEN-related Proteus-like syndrome)ADAsymmetric overgrowthVariable presentations; see PTEN hamartoma tumor syndrome for comprehensive clinical descriptions.

AD = autosomal dominant; AR = autosomal recessive; CLOVES syndrome = congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome; CNS = central nervous system; DD = developmental delay; DiffDx = differential diagnosis; ID = intellectual disability; MCAP syndrome = megalencephaly-capillary malformation syndrome; MOI = mode of inheritance; XL = X-linked

1.

Hypomethylation of the imprinted control region 1 (ICR1) at 11p15.5 causes SRS in 35%-50% of individuals, and maternal uniparental disomy (mUPD7) causes SRS in 7%-10% of individuals. A small number of affected individuals have duplications, deletions, or translocations involving the imprinting centers at 11p15.5 or duplications, deletions, or translocations involving chromosome 7. Rarely, affected individuals with pathogenic variants in CDKN1C, IGF2, PLAG1, and HMGA2 have been described.

2.

SRS typically has a low recurrence risk; however, accurate assessment of recurrence risk requires identification of the causative genetic mechanism in the affected family member.

3.

Not known to be inherited; most identified pathogenic variants are somatic (mosaic).

From: Beckwith-Wiedemann Syndrome

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.