Details of Disease

General Information of Disease (ID: DISH15GR)

• Disease Name: Beckwith-Wiedemann syndrome
• Synonyms: exomphalos macroglossia gigantism syndrome; Wiedemann-Beckwith syndrome (WBS); Beckwith-Wiedemann syndrome chromosome region; EMG syndrome; Wiedemann-Beckwith syndrome; exomphalos-macroglossia-gigantism syndrome; Beckwith-Wiedemann syndrome; BWS
• Definition: Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by overgrowth, tumor predisposition and congenital malformations.
• Disease Hierarchy:
  DISGXLG5: Hereditary neoplastic syndrome
  DISQ89HN: Familial hypertrophic cardiomyopathy
  DISHK54G: Overgrowth syndrome
  DISH15GR: Beckwith-Wiedemann syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0007534
  MESH ID: D001506
  UMLS CUI: C0004903
  OMIM ID: 130650
  MedGen ID: 2562
  Orphanet ID: 116
  SNOMED CT ID: 81780002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Dactinomycin	DM2YGNW	Approved	Small molecular drug	[1]
Doxorubicin	DMVP5YE	Approved	Small molecular drug	[2]
Etoposide	DMNH3PG	Approved	Small molecular drug	[3]
Vincristine	DMINOX3	Approved	Small molecular drug	[4]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 33 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ZNF215	OTG3Y5VJ	No Known	Unknown	[5]
CIB2	OT9ZJX1I	Limited	Biomarker	[18]
CTCF	OT8ZB70U	Limited	Genetic Variation	[19]
GRB10	OTCKXGRC	Limited	Genetic Variation	[20]
GTF2IRD1	OTEG9KU1	Limited	Biomarker	[21]
HIC1	OTI9TWY4	Limited	Genetic Variation	[22]
PHPT1	OTFYWNFX	moderate	Biomarker	[23]
SOX3	OT1CRCOB	moderate	Biomarker	[23]
AMER1	OT8EFJPM	Strong	Genetic Variation	[24]
ATAD5	OTI8ABKF	Strong	Biomarker	[25]
C11orf21	OTJGXDHK	Strong	Biomarker	[26]
CD48	OT83ZNPP	Strong	Genetic Variation	[26]
CEND1	OTPHOC22	Strong	Genetic Variation	[27]
CMTR1	OTG0N8GA	Strong	Biomarker	[14]
CORO1A	OTVAZOHC	Strong	Posttranslational Modification	[6]
DDX11	OT1WR3MD	Strong	Biomarker	[28]
GTF2I	OTUYL1TQ	Strong	Biomarker	[21]
IFT46	OTQDPBZW	Strong	Biomarker	[26]
INS-IGF2	OTZR74BO	Strong	Biomarker	[29]
LMO1	OTB59SKB	Strong	Biomarker	[30]
NLRP7	OTE9BI32	Strong	Genetic Variation	[31]
PALB2	OT6DNDBG	Strong	Genetic Variation	[32]
PGAP2	OTUW3SAX	Strong	Biomarker	[25]
PLAGL1	OTZAO900	Strong	Biomarker	[8]
RASSF7	OT0V4EIZ	Strong	Biomarker	[29]
SGCE	OT9F17JB	Strong	Biomarker	[33]
SLC22A18	OT9C3KR4	Strong	Genetic Variation	[34]
SMS	OT8JYKNH	Strong	Biomarker	[35]
SNRPN	OTQB1ID1	Strong	Genetic Variation	[36]
TBL2	OTCIMSK8	Strong	Biomarker	[37]
CDKN1C	OTASTJ3Q	Definitive	Autosomal dominant	[15]
IGF2	OTJ4O6MW	Definitive	Autosomal dominant inheritance with maternal imprinting HP:0012275	[16]
NSD1	OTLV02OJ	Definitive	Autosomal dominant	[16]

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN1C	TTBSUAR	Limited	Posttranslational Modification	[6]
DLK1	TTF4AVB	Limited	Biomarker	[7]
IGF2R	TTPNE41	Limited	Biomarker	[8]
TGM1	TT7A949	Limited	Genetic Variation	[6]
AFP	TTCFEA1	Strong	Biomarker	[9]
GPC3	TTJTSX4	Strong	Genetic Variation	[10]
KCNQ1	TT846HF	Strong	Genetic Variation	[11]
NSD1	TTTSJ3H	Strong	Genetic Variation	[12]
SPTBN1	TTS9BDA	Strong	Genetic Variation	[13]
TRPM1	TTTDAI9	Strong	Biomarker	[14]
TRPM5	TT1N8F3	Strong	Biomarker	[14]
CDKN1C	TTBSUAR	Definitive	Autosomal dominant	[15]
IGF2	TTE8WGO	Definitive	Autosomal dominant inheritance with maternal imprinting HP:0012275	[16]
KCNJ11	TT329V4	Definitive	Genetic Variation	[17]
NSD1	TTTSJ3H	Definitive	Autosomal dominant	[16]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
DIO3	DET89OV	Strong	Biomarker	[7]

References

• [1] Dactinomycin FDA Label
• [2] Doxorubicin FDA Label
• [3] Etoposide FDA Label
• [4] Vincristine FDA Label
• [5] Disruption of a novel imprinted zinc-finger gene, ZNF215, in Beckwith-Wiedemann syndrome. Am J Hum Genet. 2000 May;66(5):1473-84. doi: 10.1086/302892. Epub 2000 Apr 10.
• [6] Targeted demethylation at the CDKN1C/p57 locus induces human cell replication.J Clin Invest. 2019 Jan 2;129(1):209-214. doi: 10.1172/JCI99170. Epub 2018 Nov 26.
• [7] Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome.Epigenetics. 2019 Sep;14(9):850-876. doi: 10.1080/15592294.2019.1615357. Epub 2019 May 30.
• [8] The Frequency of Methylation Abnormalities Among Estonian Patients Selected by Clinical Diagnostic Scoring Systems for Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome.Genet Test Mol Biomarkers. 2015 Dec;19(12):684-91. doi: 10.1089/gtmb.2015.0163. Epub 2015 Oct 27.
• [9] Longitudinal Monitoring of Alpha-Fetoprotein by Dried Blood Spot for Hepatoblastoma Screening in BeckwithWiedemann Syndrome.Cancers (Basel). 2019 Jan 14;11(1):86. doi: 10.3390/cancers11010086.
• [10] GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome.Am J Med Genet. 2001 Aug 1;102(2):161-8. doi: 10.1002/1096-8628(20010801)102:2<161::aid-ajmg1453>3.0.co;2-o.
• [11] Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus.Genet Med. 2019 Aug;21(8):1808-1820. doi: 10.1038/s41436-018-0416-7. Epub 2019 Jan 12.
• [12] NSD1 duplication in Silver-Russell syndrome (SRS): molecular karyotyping in patients with SRS features.Clin Genet. 2017 Jan;91(1):73-78. doi: 10.1111/cge.12803. Epub 2016 Jun 30.
• [13] TGF-/2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.J Clin Invest. 2016 Feb;126(2):527-42. doi: 10.1172/JCI80937. Epub 2016 Jan 19.
• [14] Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression.Hum Mol Genet. 2000 Jan 22;9(2):203-16. doi: 10.1093/hmg/9.2.203.
• [15] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [16] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [17] Coexistence of Mosaic Uniparental Isodisomy and a KCNJ11 Mutation Presenting as Diffuse Congenital Hyperinsulinism and Hemihypertrophy.Horm Res Paediatr. 2016;85(6):421-5. doi: 10.1159/000446153. Epub 2016 May 14.
• [18] p57(Kip2) knock-in mouse reveals CDK-independent contribution in the development of Beckwith-Wiedemann syndrome.J Pathol. 2016 Jul;239(3):250-61. doi: 10.1002/path.4721. Epub 2016 May 4.
• [19] Is ZFP57 binding to H19/IGF2:IG-DMR affected in Silver-Russell syndrome?.Clin Epigenetics. 2018 Feb 21;10:23. doi: 10.1186/s13148-018-0454-7. eCollection 2018.
• [20] Large de novo deletion of 7p15.1 to 7p12.1 involving the imprinted gene GRB10 associated with a complex phenotype including features of Beckwith Wiedemann syndrome.Eur J Med Genet. 2011 Jan-Feb;54(1):89-93. doi: 10.1016/j.ejmg.2010.09.006. Epub 2010 Oct 8.
• [21] Transaxillary robotic modified radical neck dissection: a 5-year assessment of operative and oncologic outcomes.Surg Endosc. 2017 Apr;31(4):1599-1606. doi: 10.1007/s00464-016-5146-9. Epub 2016 Aug 29.
• [22] Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice.PLoS Genet. 2018 Feb 22;14(2):e1007243. doi: 10.1371/journal.pgen.1007243. eCollection 2018 Feb.
• [23] New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism.Eur J Endocrinol. 2010 Dec;163(6):953-62. doi: 10.1530/EJE-10-0435. Epub 2010 Sep 13.
• [24] Inactivation of the APC gene is constant in adrenocortical tumors from patients with familial adenomatous polyposis but not frequent in sporadic adrenocortical cancers.Clin Cancer Res. 2010 Nov 1;16(21):5133-41. doi: 10.1158/1078-0432.CCR-10-1497. Epub 2010 Oct 26.
• [25] Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer.Genomics. 1999 Nov 15;62(1):59-66. doi: 10.1006/geno.1999.5980.
• [26] C11orf21, a novel gene within the Beckwith-Wiedemann syndrome region in human chromosome 11p15.5.Gene. 2000 Oct 3;256(1-2):311-7. doi: 10.1016/s0378-1119(00)00377-2.
• [27] Cloning, expression and localization of human BM88 shows that it maps to chromosome 11p15.5, a region implicated in Beckwith-Wiedemann syndrome and tumorigenesis.Biochem J. 2001 May 1;355(Pt 3):715-24. doi: 10.1042/bj3550715.
• [28] Warsaw breakage syndrome: Further clinical and genetic delineation.Am J Med Genet A. 2018 Nov;176(11):2404-2418. doi: 10.1002/ajmg.a.40482. Epub 2018 Sep 14.
• [29] Duplication of HRAS1, INS, and IGF2 is not a common event in Beckwith-Wiedemann syndrome.Ann Genet. 1988;31(4):216-20.
• [30] Reassessment of breakpoints in chromosome 11p15.Cytogenet Cell Genet. 1993;62(1):52-3. doi: 10.1159/000133444.
• [31] Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome). PLoS Genet. 2009 Mar;5(3):e1000423. doi: 10.1371/journal.pgen.1000423. Epub 2009 Mar 20.
• [32] Genomic profiles of a hepatoblastoma from a patient with Beckwith-Wiedemann syndrome with uniparental disomy on chromosome 11p15 and germline mutation of APC and PALB2.Oncotarget. 2017 Aug 24;8(54):91950-91957. doi: 10.18632/oncotarget.20515. eCollection 2017 Nov 3.
• [33] Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.J Hum Genet. 2013 Sep;58(9):604-10. doi: 10.1038/jhg.2013.67. Epub 2013 Jun 27.
• [34] Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples.Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3873-8. doi: 10.1073/pnas.95.7.3873.
• [35] Human diseases versus mouse models: insights into the regulation of genomic imprinting at the human 11p15/mouse distal chromosome 7 region.J Med Genet. 2013 Jan;50(1):11-20. doi: 10.1136/jmedgenet-2012-101321.
• [36] The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region.J Med Genet. 2006 Dec;43(12):902-7. doi: 10.1136/jmg.2006.042135. Epub 2006 Jul 6.
• [37] TBL2, a novel transducin family member in the WBS deletion: characterization of the complete sequence, genomic structure, transcriptional variants and the mouse ortholog.Cytogenet Cell Genet. 1999;86(3-4):277-84. doi: 10.1159/000015319.