Tumour surveillance in Beckwith-Wiedemann syndrome and Hemihyperplasia (Hemihypertrophy)
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There has long been a recognised relationship between disorders of increased somatic growth and predisposition to cancer.
Two related syndromes in particular are associated with cancer predisposition:
Isolated Hemihyperplasia (IHH)
Both are linked to a significantly increased risk of developing abdominal tumours, including Wilms Tumour (WT), hepatoblastoma and adrenal cell carcinoma.
Of the tumours in BWS, 43% are Wilms Tumour, 20% hepatoblastoma and 7% adrenal cell carcinoma.
Screening may result in early stage disease and smaller tumours being detected (8).
"Asymmetric overgrowth of one or more of the cranium, face, trunk and limbs, with or without visceral involvement" (13).
- HH of limbs involves discrepancy in both length and circumference of affected limbs.
- HH may affect segmental regions of the body or selected organs and tissues.
- There is no consensus about which regions of the body can be involved and the degree of asymmetry required to make the diagnosis (13).
- The asymmetry often becomes more pronounced with age. Growth rate usually slows around age 7-8 years.
- HH can be a feature of BWS or an isolated finding (IHH).
- The frequency of HH in the general population has been reported between 1:53,000 and 1:86,000. The frequency is 2.01:100 among children with Wilms tumour.
- For children with HH, the risk of WT is approximately 3% (3).
- Neoplasia (WT/hepatoblastoma/adrenal cell carcinoma) risk for HH has been reported as 5.9% (7).
- Children with HH were (1993) less likely (32%) to be diagnosed with HH before the diagnosis of WT, but with raised awareness HH is often diagnosed first (3)
Beckwith-Wiedemann Syndrome (BWS)
- The incidence of BWS has been estimated to be 1:13,700 births with 85% sporadic and 15% familial (5). For children with BWS, the risk of neoplasia has been reported between 7.5% (1) and 21% (5) and is highest in the first decade of life (6)
- However most children with BWS do not develop tumours, and the risk declines with age. After 10 years, the risk approaches the baseline risk of cancer in the general population.
- Several studies have demonstrated that children with both BWS and HH have a higher risk (40%) of WT than children with either condition alone (1,6,10)
- Children with BWS screened for WT were much less likely (0 /12) to present with advanced disease than those who were not screened (25/ 59)(8), potentially allowing for nephron sparing surgery (11).
- BWS has a wide clinical spectrum including several variable associated anomalies. The variability of BWS clinical picture is paralleled by comparable (Epi) genetic heterogeneity at the molecular level.
- In recent studies (2015, 2016), tumour occurrence was dependent on genotype. Cancer risk was lower in IC2/CDKN1C, intermediate risk in UPD and very high in IC1 cases (16,17). Where genotype known, screening to be modified - see Table B.
- Screening for abdominal tumour (renal,adrenal,hepatic,pancreatic) by regular abdominal ultrasound examination is recommended for children with BWS, HH, or both. A scan interval of 3-4 months is recommended, as interval tumours have been reported with scan intervals in excess of 4-6 months (2). This is due to the rapid Wilms Tumour growth rate with a doubling time estimated between 11-40 days (9,13).
- Various surveillance protocols for these children have been proposed with the aim to reduce morbidity and mortality from cancer in children with BWS and isolated HH.
- Surveillance is targeted at detecting embryonal tumours, particularly Wilms tumour and hepatoblastoma. Screening of serum alpha-fetoprotein is recommended in children with BWS or IHH to detect hepatoblastoma.
There are no serum tumour markers that will detect Wilms Tumour (12).
Table A: Recommendation for screening in IHH and BWS (13-15)
|Tumour surveillance||Frequency||Until age|
|Abdominal ultrasound||3 monthly||8 years|
|Serum alpha-fetoprotein||6 weekly - 3 monthly #||4 years|
|Complete physical examination including abdominal palpation by a physician||6 monthly ^||Indefinite|
# Data regarding optimal frequency are lacking, but if the AFP
is elevated, increase index of suspicion and repeat sampling one
month later is indicated
^ Data regarding optimal frequency are lacking
|Genotype||Tumour surveillance||Frequency||Until age|
|IC1 methylation||Wilms tumour - renal ultrasound||3 monthly||5 years|
|pUPD||Wilms tumour - renal ultrasound
Hepatoblastoma - abdominal ultrasound
|No detectable molecular defect||Wilms tumour - renal ultrasound
Hepatoblastoma - abdominal ultrasound
Wilms tumour - renal ultrasound
Hepatoblastoma - abdominal ultrasound
Neuroblastoma - urinary dopamine/HVA
- Wiedemann HR. Tumors and hemihypertrophy associated with the Wiedemann-Beckwith syndrome.European Journal Pediatrics 1983;141:129
- Azouz EM, Larson EJ, Patel J, Gyepes MT. Beckwith-Wiedemann syndrome: development of nephroblastoma during the surveillance period.Pediatric Radiology 1990;20(7):550-2
- Green DM, Breslow NE, Beckwith JB, Norkool P. Screening of children with hemihypertrophy, aniridia and Beckwith-Wiedemann syndrome in patients with Wilms Tumor: a report from the National Wilms Tumor Study (NWTS). Medical and Pediatric Oncology 1993;21(3):188-92
- Craft AW, Parker L, Stiller C, Cole M. Screening for Wilms tumour in patients with aniridia, Beckwith syndrome of hemihypertrophy.Medical and Pediatric Oncology 1995 April;24(4):231-4
- Schneid H, Vazquez MP, Vacher C, Gourmelen M, Cabrol S, Le Bouc Y. The Beckwith-Wiedemann Syndrome Phenotype and the Risk of Cancer.Medical and Pediatric Oncology 1997 June;28(6):411-415
- DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children with the Beckwith-Wiedemann Syndrome Registry.J Pediatrics, 1998 Mar; 132(3 Pt1):398-400 ( Comment on pages 377-9)
- Hoyme HE, Seaver LH, Jones KL, Procopio F, Crooks W, Feingold M. Isolated hemihyperplasia (IHH) (hemihypertrophy): report of a prospective multicentre study of the incidence of neoplasia and review.American Journal of Medical Genetics 1998: 79(4):274-8
- Choyke PL, Siegel MJ, Craft AW, Green DM, De Baun MR. Screening for Wilms tumor in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy. Medical and Pediatric Oncology 1999 March; 32(3):196-200
- Craft AW. Growth rate of Wilms' Tumour. Lancet 1999; 354: 1127
- 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 Genetics 2002; 70 604-11
- McNeil DE, Langer JC, Choyke P, De Baun MR. Feasibility of partial nephrectomy for Wilms tumor in children with Beckwith-Wiedemann syndrome who have been screened with abdominal ultrasonography.Journal Pediatric Surgery 2002 January; 37(1):57-60
- Clericuzio CL, Chen E, McNeil DE et al. Serum alphafetoprotein screening for hepatoblastoma in children with BWS and isolated hemihypertrophy. J Pediatr 2003; 143: 270-272
- Tani TY, Amor DJ. Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia:A critical review of the evidence and suggested guidelines for local practice. Journal of Paediatrics and Child Health 42 (2006) 486-490
- Teplick A, Kowalski M, Biegel JA, Nichols KE. Screening in cancer predisposition syndromes: guidelines for the general paediatrician. Eur J Pediatr 2011 170: 285-294
- Samuel N, Villani A, Fernandez CV and Malkin D. Management of familial cancer: sequencing, surveillance and society. Nature Reviews/Clinical Oncology 11, December (2014) 723-731
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- Date last published: 31 August 2017
- Document type: Clinical Guideline
- Services responsible: Paediatric Endocrinology, Paediatric Radiology, Paediatric Haematology/Oncology, Genetics
- Author(s): Craig Jefferies, Rita Teele, Jane Skeen, Juliet Taylor
- Editor: Greg Williams
- Review frequency: 2 years
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