FaCD Online Syndrome Fact Sheet

Last updated: 23 Jun 2011

Name: Beckwith-Wiedemann syndrome

Synonym: BWS, Exomphalos-Macroglossia-Gigantism (EMG) syndrome, Wiedemann-Beckwith syndrome, WBS

Mode of Inheritance: AD/ spor/ impr (UPDpat11)

Genes

H19, mapped to 11p15.5
LIT1/KCNQ1OT1, mapped to 11p15.5
NSD1, mapped to 5q35
p57/kip2/CDKN1C, mapped to 11p15.5

Tumor features

adrenal adenoma
adrenocortical cancer
hepatoblastoma
nephroblastomatosis
neuroblastoma, adrenal
pancreatoblastoma
Wilms' tumor (nephroblastoma)

Tumor features (possible)

atypical teratoid/rhabdoid tumor of the CNS
carcinoid of the small intestine
cardiac tumor
ganglioneuroma(tosis)
gastric teratoma
glioblastoma (multiforme)
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
lipoma
lymphoma, malignant (Non-Hodgkin and/or Hodgkin)
mesenchymal hamartoma of the liver
neuroblastoma, extra-adrenal
ovarian gonadoblastoma
perineurioma
pheochromocytoma
rhabdomyosarcoma
testicular gonadoblastoma
umbilical myxoma

Non-tumor features

ear-lobe grooves
flame nevus
gigantism/overgrowth
heart, congenital defect
helix, indentations on posterior rim
hemihypertrophy
omphalocele
seizures
skeletal anomalies
tongue, macroglossia
transitory hypoglycemia

Comment

Gigantism, macroglossia, omphalocele and ear creases are the typical features of the syndrome[1-4]. Pancreatic hyperplasia often occurs and leads to neonatal hypoglycemia in 30-50 % of cases. Approximately 5 % of children with this disorder develop tumors before the age of 8 years, mainly Wilms tumor (60%), hepatoblastoma and neuroblastoma, but a range of other tumors has been reported[2;5-19,22-25]. Limb asymmetry/hemihypertrophy is associated with an increased risk of tumors[10;11] and nephromegaly appears to be a predictor of Wilms tumor, particularly in these patients[12].

The genetics of BWS are relatively complex (check the OMIM link). Cooper et al analysed genotype-cancer phenotype associations and concluded that the risk of neoplasia was significantly higher in UPD and IC1 defect cases than in IC2 defect and CDKN1C mutation cases. Cancer risk for all patients was estimated at 9% at age 5 years, and 24% in the UPD subgroup. UPD including WT1 was associated with renal neoplasia. In contrast, Wilms' tumor risk in the IC2 defect subgroup appears to be small[20]. Rump et al concluded that increased tumor risk in BWS is typically associated with loss of imprinting of H19[21]

Links

The Beckwith-Wiedemann Family Forum 24 1 08

References

[1] Cohen PR, Kurzrock R. Miscellaneous genodermatoses: Beckwith-Wiedemann syndrome, Birt- Hogg-Dube syndrome, familial atypical multiple mole melanoma syndrome, hereditary tylosis, incontinentia pigmenti, and supernumerary nipples. Dermatol Clin 1995; 13(1):211-229.
[2] Beckwith JB. Vignettes from the history of overgrowth and related syndromes. Am J Med Genet 79[4], 238-248. 1998.
[3] Kosseff AL, Herrmann J, Gilbert EF, Viseskul C, Lubinsky M, Opitz JM. Studies of malformation syndromes of man XXIX: the Wiedemann- Beckwith syndrome. Clinical, genetic and pathogenetic studies of 12 cases. Eur J Pediatr 1976; 123(3):139-166.
[4] Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD. Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet 1986; 74:143-154.
[5] Berx G, Becker KF, Hofler H, Van Roy F. Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 12, 226-237. 1998.
[6] Falik-Borenstein TC, Korenberg JR, Davos I, Platt LD, Gans S, Goodman B, Schreck R, Graham JM, Jr. Congenital gastric teratoma in Wiedemann-Beckwith syndrome. Am J Med Genet 1991; 38:52-57.
[7] Emery LG, Shields M, Shah NR, Garbes A. Neuroblastoma associated with Beckwith-Wiedemann syndrome. Cancer 1983; 52:176-179.
[8] Drut R, Jones MC. Congenital pancreatoblastoma in Beckwith-Wiedemann syndrome: An emerging association. Pediatr Pathol 8, 331-339. 1988.
[9] Sotelo-Avila C, Gooch III WM. Neoplasms associated with the Beckwith-Wiedemann Syndrome. In: Rosenberg HS, editor. Perspectives in pediatric pathology. Chicago: Year Book Med Publ, 1973: 255-272.
[10] Wiedemann HR. Tumours and hemihyperstrophy associated with Wiedemann-Beckwith syndrome. Eur J Pediatr 1983; 141:129.
[11] De Baun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediat 132[3], 398-400. 1998.
[12] Debaun MR, Siegel MJ, Choyke PL. Nephromegaly in infancy and early childhood: A risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J Pediat 132[3], 401-404. 1998.
[13] Muguerza R, Rodriguez A, Formigo E, Montero M, Vázquez JL, Páramo C, Campos C. Pancreatoblastoma associated with incomplete Beckwith-Wiedemann syndrome: case report and review of the literature. Journal of pediatric surgery 2005; 40(8):1341-4.
[14] Cajaiba MM, Sarita-Reyes C, Zambrano E, Reyes-Múgica M. Mesenchymal hamartoma of the liver associated with features of Beckwith-Wiedemann syndrome and high serum alpha-fetoprotein levels. Pediatric and developmental pathology 2007 May-Jun; 10(3):233-8.
[15] Chen L, Li Y, Lin JH. Intraneural perineurioma in a child with Beckwith-Wiedemann syndrome. Journal of pediatric surgery 2005; 40(2):E12-4.
[16] Baldisserotto M, Peletti AB, Angelo de Araújo M, Pertence AP, Dora MD, Maciel EO, Gaiger AM. Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings. Pediatric radiology 2005; 35(11):1132-4.
[17] Khatib Z, Levi A, Pefkarou A, Escalon E. Acute lymphocytic leukemia in a child with Beckwith-Wiedemann syndrome. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2004; 26(1):45-7.
[18] Satgé D, Vidalo E, Desfarges F, de Geeter B. A third case of cardiac neoplasm in a fetus with Beckwith-Wiedemann syndrome: epicardial angiofibroma. Fetal diagnosis and therapy 2005 Jan-Feb; 20(1):44-7.
[19] Houtenbos I, Ossenkoppele GJ. Acute myeloid leukemia in a 23-year-old patient with Beckwith-Wiedemann syndrome. Cancer genetics and cytogenetics 2002; 136(1):90-1.
[20] Cooper WN, Luharia A, Evans GA, Raza H, Haire AC, Grundy R, Bowdin SC, Riccio A, Sebastio G, Bliek J, Schofield PN, Reik W, Macdonald F, Maher ER. Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. European journal of human genetics : EJHG 2005; 13(9):1025-32.
[21] Rump P, Zeegers MP, van Essen AJ. Tumor risk in Beckwith-Wiedemann syndrome: A review and meta-analysis. American journal of medical genetics. Part A 2005; 136(1):95-104.
[22] Alsultan A, Lovell MA, Hayes KL, Allshouse MJ, Garrington TP. Simultaneous occurrence of right adrenocortical tumor and left adrenal neuroblastoma in an infant with Beckwith-Wiedemann syndrome. Pediatr Blood Cancer. 2008 Nov;51(5):695-8.
[23] Borny F, Mortelé B, Seynaeve P. Multifocal nephroblastomatosis in Beckwith-Wiedemann syndrome. JBR-BTR. 2009 May-Jun;92(3):144-5.
[24] Kuroiwa M, Sakamoto J, Shimada A, Suzuki N, Hirato J, Park MJ, Sotomatsu M, Hayashi Y. Manifestation of alveolar rhabdomyosarcoma as primary cutaneous lesions in a neonate with Beckwith-Wiedemann syndrome. Pediatr Surg. 2009 Mar;44(3):e31-5.
[25] Jackson EM, Shaikh TH, Zhang F, Wainwright LM, Storm PB, Hakonarson H, Zackai EH, Biegel JA. Atypical teratoid/rhabdoid tumor in a patient with Beckwith-Wiedemann syndrome. Am J Med Genet A. 2007 Aug 1;143A(15):1767-70.