Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 2 , Pages 96-102, June 2007

Syndromes and Disorders Associated with Omphalocele (I): Beckwith–Wiedemann Syndrome

  • Chih-Ping Chen

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan

Departments of Obstetrics and Gynecology, and Medical Research, Mackay Memorial Hospital, Taipei, Department of Biotechnology and Bioinformatics, Asia University, and College of Chinese Medicine, China Medical University, Taichung, Taiwan

Accepted 1 March 2007.

Article Outline

Summary 

Beckwith–Wiedemann syndrome (BWS, OMIM 130650) is characterized by macrosomia, macroglossia, visceromegaly, hemihypertrophy, abdominal wall defects, ear creases/pits, neonatal hypoglycemia, polyhydramnios, placentomegaly, placental mesenchymal dysplasia, cardiac defects, nevus flammeus, hemangiomata, and an increased frequency of embryonal tumors. This article provides an overview of BWS including the genetics, genetic diagnosis, genotype/epigenotype–phenotype correlations, association with assisted reproductive technology, and prenatal diagnosis. Omphalocele is an important sonographic marker for BWS. Prenatal detection of omphalocele, fetal overgrowth, polyhydramnios, increased abdominal circumference, placentomegaly and/or placental mesenchymal dysplasia should alert one to the possibility of BWS and prompt a genetic investigation and counseling for BWS.

Key Words:  Beckwith–Wiedemann syndrome , genetics , omphalocele

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References 

  1. Elliott M , Bayly R , Cole T , Temple IK , Maher ER . Clinical features and natural history of Beckwith–Wiedemann syndrome: presentation of 74 new cases . Clin Genet . 1994;46:168–174
  2. Weksberg R , Smith AC , Squire J , Sadowski P . Beckwith– Wiedemann syndrome demonstrates a role for epigenetic control of normal development . Hum Mol Genet . 2003;12(Suppl 1):R61–R68
  3. Weksberg R , Shuman C , Smith AC . Beckwith–Wiedemann syndrome . Am J Med Genet . 2005;137C:12–23
  4. Hao Y , Crenshaw T , Moulton T , Newcomb E , Tycko B . Tumour-suppressor activity of H19 RNA . Nature . 1993;365:764–767
  5. Bell AC , West AG , Felsenfeld G . The protein CTCF is required for the enhancer blocking activity of vertebrate insulators . Cell . 1999;98:387–396
  6. Lee MP , Hu RJ , Johnson LA , Feinberg AP . Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith–Wiedemann syndrome chromosomal rearrangements . Nat Genet . 1997;15:181–185
  7. Smilinich NJ , Day CD , Fitzpatrick GV , et al.   A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith–Wiedemann syndrome . Proc Natl Acad Sci USA . 1999;96:8064–8069
  8. Lee MP, DeBaun MR, Mitsuya K, Galonek HL, Brandenburg S, Oshimura M, et al. Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith–Wiedemann syndrome and is independent of insulin-like growth factor II imprinting . Proc Natl Acad Sci USA . 1999;96:5203–5208
  9. Gaston V , Le Bouc Y , Soupre V , et al.   Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith– Wiedemann syndrome . Eur J Hum Genet . 2001;9:409–418
  10. Bliek J, Maas SM, Ruijter JM, Hennekam RC, Alders M, Westerveld A, et al. Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS . Hum Mol Genet . 2001;10:467–476
  11. Lee MH , Reynisdottir I , Massague J . Cloning of p57(KIP2), a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution . Genes Dev . 1995;9:639–649
  12. Hatada I , Ohashi H , Fukushima Y , et al.   An imprinted gene p57(KIP2) is mutated in Beckwith–Wiedemann syndrome . Nat Genet . 1996;14:171–173
  13. Lam WW , Hatada I , Ohishi S , et al.   Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith–Wiedemann syndrome (BWS) provides a novel genotype–phenotype correlation . J Med Genet . 1999;36:518–523
  14. Li M , Squire J , Shuman C , et al.   Imprinting status of 11p15 genes in Beckwith–Wiedemann syndrome patients with CDKN1C mutations . Genomics . 2001;74:370–376
  15. Baujat G , Rio M , Rossignol S , et al.   Paradoxical NSD1 mutations in Beckwith–Wiedemann syndrome and 11p15 anomalies in Sotos syndrome . Am J Hum Genet . 2004;74:715–720
  16. Altug-Teber O , Dufke A , Poths S , et al.   A rapid microarray based whole genome analysis for detection of uniparental disomy . Hum Mutat . 2005;26:153–159
  17. Schulz R , Menheniott TR , Woodfine K , Wood AJ , Choi JD , Oakey RJ . Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies . Nucleic Acids Res . 2006;34:e88
  18. Coffee B , Muralidharan K , Highsmith WE , Lapunzina P , Warren ST . Molecular diagnosis of Beckwith–Wiedemann syndrome using quantitative methylation-sensitive polymerase chain reaction . Genet Med . 2006;8:628–634
  19. Engel JR , Smallwood A , Harper A , et al.   Epigenotype– phenotype correlations in Beckwith–Wiedemann syndrome . J Med Genet . 2000;37:921–926
  20. Weksberg R , Nishikawa J , Caluseriu O , et al.   Tumor development in the Beckwith–Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1 . Hum Mol Genet . 2001;10:2989–3000
  21. DeBaun MR , Niemitz EL , McNeil DE , Brandenburg SA , Lee MP , Feinberg AP . Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith–Wiedemann syndrome with cancer and birth defects . Am J Hum Genet . 2002;70:604–611
  22. Cooper WN , Luharia A , Evans GA , et al.   Molecular sub-types and phenotypic expression of Beckwith–Wiedemann syndrome . Eur J Hum Genet . 2005;13:1025–1032
  23. Smith AC , Rubin T , Shuman C , et al.   New chromosome 11p15 epigenotypes identified in male monozygotic twins with Beckwith–Wiedemann syndrome . Cytogenet Genome Res . 2006;113:313–317
  24. Weksberg R , Shuman C , Caluseriu O , et al.   Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith–Wiedemann syndrome . Hum Mol Genet . 2002;11:1317–1325
  25. Lubinsky MS , Hall JG . Genomic imprinting, monozygous twinning, and X inactivation . Lancet . 1991;337:1288
  26. DeBaun MR , Niemitz EL , Feinberg AP . Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epi-genetic alterations of LIT1 and H19 . Am J Hum Genet . 2003;72:156–160
  27. Gicquel C , Gaston V , Mandelbaum J , Siffroi JP , Flahault A , Le Bouc Y . In vitro fertilization may increase the risk of Beckwith–Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene . Am J Hum Genet . 2003;72:1338–1341
  28. Maher ER , Brueton LA , Bowdin SC , et al.   Beckwith– Wiedemann syndrome and assisted reproduction technology (ART) . J Med Genet . 2003;40:62–64
  29. Halliday J , Oke K , Breheny S , Algar E , J Amor D . Beckwith– Wiedemann syndrome and IVF: a case-control study . Am J Hum Genet . 2004;75:526–528
  30. Rossignol S , Steunou V , Chalas C , et al.   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;43:902–907
  31. Sutcliffe AG , Peters CJ , Bowdin S , et al.   Assisted reproductive therapies and imprinting disorders: a preliminary British survey . Hum Reprod . 2006;21:1009–1011
  32. Chang AS , Moley KH , Wangler M , Feinberg AP , DeBaun MR . Association between Beckwith–Wiedemann syndrome and assisted reproductive technology: a case series of 19 patients . Fertil Steril . 2005;83:349–354
  33. Menezo Y , Viville S , Veiga A . Epigenetics and assisted reproductive technology . Fertil Steril . 2006;85:269
  34. Menezo Y , Khatchadourian C , Gharib A , Hamidi J , Greenland T , Sarda N . Regulation of S-adenosyl methionine synthesis in the mouse embryo . Life Sci . 1989;44:1601–1609
  35. Wolff GL , Kodell RL , Moore SR , Cooney CA . Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice . FASEB J . 1998;12:949–957
  36. Niemitz EL , Feinberg AP . Epigenetics and assisted reproductive technology: a call for investigation . Am J Hum Genet . 2004;74:599–609
  37. Ludwig M , Katalinic A , Gross S , Sutcliffe A , Varon R , Horsthemke B . Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples . J Med Genet . 2005;42:289–291
  38. Chen CP , Lin SP , Hwu YM , Chang TY , Wang W . Prenatal identification of fetal overgrowth, abdominal wall defect, and neural tube defect in pregnancies achieved by assisted reproductive technology . Prenat Diagn . 2004;24:396–398
  39. Williams DH , Gauthier DW , Maizels M . Prenatal diagnosis of Beckwith–Wiedemann syndrome . Prenat Diagn . 2005;25:879–884
  40. Cohen MM . Beckwith–Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives . Pediatr Develop Pathol . 2005;8:287–304
  41. Wiedemann HR . Tumours and hemihypertrophy associated with Wiedemann–Beckwith syndrome . Eur J Pediatr . 1983;141:129
  42. DeBaun MR , Tucker MA . Risk of cancer during the first four years of life in children from the Beckwith–Wiedemann syndrome registry . J Pediatr . 1998;132:398–400
  43. Merrot T , Walz J , Anastasescu R , Chaumoitre K , D'Ercole C . Prenatally detected cystic adrenal mass associated with Beckwith–Wiedemann syndrome . Fetal Diagn Ther . 2004;19:465–469
  44. Gocmen R, Basaran C, Karcaaltincaba M, Cinar A, Yurdakok M, Akata D, et al. Bilateral hemorrhagic adrenal cysts in an incomplete form of Beckwith–Wiedemann syndrome: MRI and prenatal US findings . Abdom Imaging . 2005;30:786–789
  45. Izbizky G , Elias D , Gallo A , Farias P , Sod R . Prenatal diagnosis of fetal bilateral adrenal carcinoma . Ultrasound Obstet Gynecol . 2005;26:669–671
  46. Fremond B , Poulain P , Odent S , Milon J , Treguier C , Babut JM . Prenatal detection of a congenital pancreatic cyst and Beckwith–Wiedemann syndrome . Prenat Diagn . 1997;17:276–280
  47. Pelizzo G , Conoscenti G , Kalache KD , Vesce F , Guerrini P , Cavazzini L . Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith–Wiedemann syndrome . Prenat Diagn . 2003;23:292–294
  48. Mulik V , Wellesley D , Sawdy R , Howe DT . Unusual prenatal presentation of Beckwith–Wiedemann syndrome . Prenat Diagn . 2004;24:501–503
  49. Drut RM , Drut R . Nonimmune fetal hydrops and placentomegaly: diagnosis of familial Wiedemann–Beckwith syndrome with trisomy 11p15 using FISH . Am J Med Genet . 1996;62:145–149
  50. Lage JM . Placentomegaly with massive hydrops of placental stem villi, diploid DNA content, and fetal omphaloceles: Possible association with Beckwith–Wiedemann syndrome . Hum Pathol . 1991;22:591–597
  51. McCowan LME , Becroft DMO . Beckwith–Wiedemann syndrome, placental abnormalities, and gestational proteinuric hypertension . Obstet Gynecol . 1994;83:813–817
  52. Hillstrom MM , Brown DL , Wilkins-Haug L , Genest DR . Sonographic appearance of placental villous hydrops associated with Beckwith–Wiedemann syndrome . J Ultrasound Med . 1995;14:61–64
  53. Moscoso G , Jauniaux E , Hustin J . Placental vascular anomaly with diffuse mesenchymal stem villous hyperplasia: a new clinicopathological entity? . Pathol Res Pract . 1991;187:324–328
  54. Sander CM . Angiomatous malformation of placental chorionic stem vessels and pseudo-partial molar placentas: report of five cases . Pediatr Pathol . 1993;13:621–633
  55. Chen CP , Chern SR , Wang TY , Huang ZD , Huang MC , Chuang CY . Pregnancy with concomitant chorangioma and placental vascular malformation with mesenchymal hyper-plasia . Hum Reprod . 1997;12:2553–2556
  56. Jauniaux E , Nicolaides KH , Hustin J . Perinatal features associated with placental mesenchymal dysplasia . Placenta . 1997;18:701–706
  57. Parveen Z , Tongson-Ignacio JE , Fraser CR , Killeen JL , Thompson KS . Placental mesenchymal dysplasia . Arch Pathol Lab Med . 2007;131:131–137
  58. Cohen MC , Roper EC , Sebire NJ , Stanek J , Anumba DO . Placental mesenchymal dysplasia associated with fetal aneuploidy . Prenat Diagn . 2005;25:187–192
  59. Paradinas FJ, Sebire NJ, Fisher RA, Rees HC, Foskett M, Seckl MJ, et al. Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles . Histopathology . 2001;39:447–454
  60. Chan YF , Sampson A . Placental mesenchymal dysplasia: a report of four cases with differentiation from partial hydatidiform mole . Aust NZ J Obstet Gynaecol . 2003;43:475–479
  61. Pham T , Steele J , Stayboldt C , Chan L , Benirschke K . Placental mesenchymal dysplasia is associated with high rates of intrauterine growth restriction and fetal demise: a report of 11 new cases and a review of the literature . Am J Clin Pathol . 2006;126:67–78
  62. Reish O, Lerer I, Amiel A, Heyman E, Herman A, Dolfin T, et al. Wiedemann–Beckwith syndrome: further prenatal characterization of the condition . Am J Med Genet . 2002;107:209–213
  63. Grati FR , Turolla L , D'Ajello P , et al.   Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype–genotype correlations in Beckwith–Wiedemann syndrome . J Med Genet . 2007;44:257–263

PII: S1028-4559(07)60002-3

doi:10.1016/S1028-4559(07)60002-3

Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 2 , Pages 96-102, June 2007

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