Skip to main content
Erschienen in: Pediatric Nephrology 3/2012

01.03.2012 | Original Article

Nephrological findings and genotype–phenotype correlation in Beckwith–Wiedemann syndrome

verfasst von: Alessandro Mussa, Licia Peruzzi, Nicoletta Chiesa, Agostina De Crescenzo, Silvia Russo, Daniela Melis, Luigi Tarani, Giuseppina Baldassarre, Lidia Larizza, Andrea Riccio, Margherita Silengo, Giovanni Battista Ferrero

Erschienen in: Pediatric Nephrology | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Beckwith–Wiedemann syndrome (BWS), an overgrowth disorder with several congenital abnormalities, encompasses nephrourological anomalies. The objective of the report is to analyze the latter and related genotype–phenotype correlations. The study was a retrospective review of nephrourological investigations and genotype in 67 BWS patients. Imaging and laboratory studies have been correlated with the molecular anomalies typical of BWS. Thirty-eight (56.7%) patients had a total of 61 nonmalignant nephrourological findings, including nephromegaly (n = 24), collecting system abnormalities (n = 14), cryptorchidism (n = 11), nephrolithiasis (n = 5), cysts (n = 5), and dysplasia (n = 1). Four patients had Wilms’ tumor, all associated with renal hyperplasia. Renal findings were almost consistent in the BWSIC1 group, with nephromegaly in all patients and collecting system abnormalities in half of them. BWSUPD and negative patients also had frequent anomalies (63.6% and 61.9% respectively), whereas only 36.0% of BWSIC2 had renal findings (p = 0.003). Cryptorchidism was associated with abdominal wall defects (p < 0.001) appearing more frequently in BWSIC2 (p = 0.028). Urinary tract infections were observed in 17.9% of patients, with two resulting in life-threatening sepsis. Hypercalciuria was present in 10% of cases. 55.5% of BWS patients have renal findings. Although variegate, these anomalies disclose a genotype–phenotype correlation.
Literatur
1.
Zurück zum Zitat Choufani S, Shuman C, Weksberg R (2010) Beckwith-Wiedemann syndrome. Am J Med Genet Semin Med Genet C 154:343–354CrossRef Choufani S, Shuman C, Weksberg R (2010) Beckwith-Wiedemann syndrome. Am J Med Genet Semin Med Genet C 154:343–354CrossRef
2.
Zurück zum Zitat 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 (2005) Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. Eur J Hum Genet 13:1025–1032PubMedCrossRef 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 (2005) Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. Eur J Hum Genet 13:1025–1032PubMedCrossRef
4.
Zurück zum Zitat Bliek J, Gicquel C, Maas S, Gaston V, Le Bouc Y, Mannens M (2004) Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS). J Pediatr 145:796–799PubMedCrossRef Bliek J, Gicquel C, Maas S, Gaston V, Le Bouc Y, Mannens M (2004) Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS). J Pediatr 145:796–799PubMedCrossRef
5.
Zurück zum Zitat DeBaun MR, Siegel MJ, Choyke PL (1998) Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J Pediatr 132:401–404PubMedCrossRef DeBaun MR, Siegel MJ, Choyke PL (1998) Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J Pediatr 132:401–404PubMedCrossRef
6.
Zurück zum Zitat Rump P, Zeegers MP, van Essen AJ (1994) Tumor risk in Beckwith-Wiedemann syndrome: a review and meta-analysis. Am J Med Genet A 136:95–104 Rump P, Zeegers MP, van Essen AJ (1994) Tumor risk in Beckwith-Wiedemann syndrome: a review and meta-analysis. Am J Med Genet A 136:95–104
7.
Zurück zum Zitat Scott RH, Walker L, Olsen ØE, Levitt G, Kenney I, Maher E, Owens CM, Pritchard-Jones K, Craft A, Rahman N (2006) Surveillance for Wilms tumor in at-risk children: pragmatic recommendations for best practice. Arch Dis Child 91:995–999PubMedCrossRef Scott RH, Walker L, Olsen ØE, Levitt G, Kenney I, Maher E, Owens CM, Pritchard-Jones K, Craft A, Rahman N (2006) Surveillance for Wilms tumor in at-risk children: pragmatic recommendations for best practice. Arch Dis Child 91:995–999PubMedCrossRef
9.
Zurück zum Zitat DeBaun MR, Tucker MA (1998) Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr 132:398–400PubMedCrossRef DeBaun MR, Tucker MA (1998) Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr 132:398–400PubMedCrossRef
10.
Zurück zum Zitat Borer JG, Kaefer M, Barnewolt CE, Elias ER, Hobbs N, Retik AB, Peters CA (1999) Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome. J Urol 161:235–239PubMedCrossRef Borer JG, Kaefer M, Barnewolt CE, Elias ER, Hobbs N, Retik AB, Peters CA (1999) Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome. J Urol 161:235–239PubMedCrossRef
11.
Zurück zum Zitat McNeil DE, Langer JC, Choyke P, DeBaun MR (2002) Feasibility of partial nephrectomy for Wilms’ tumor in children with Beckwith-Wiedemann syndrome who have been screened with abdominal ultrasonography. J Pediatr Surg 37:57–60PubMedCrossRef McNeil DE, Langer JC, Choyke P, DeBaun MR (2002) Feasibility of partial nephrectomy for Wilms’ tumor in children with Beckwith-Wiedemann syndrome who have been screened with abdominal ultrasonography. J Pediatr Surg 37:57–60PubMedCrossRef
12.
Zurück zum Zitat Choyke PL, Siegel MJ, Oz O, Sotelo-Avila C, DeBaun MR (1998) Non malignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome. AJR Am J Roentgenol 171:733–737PubMed Choyke PL, Siegel MJ, Oz O, Sotelo-Avila C, DeBaun MR (1998) Non malignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome. AJR Am J Roentgenol 171:733–737PubMed
13.
Zurück zum Zitat Goldman M, Shuman C, Weksberg R, Rosenblum ND (2003) Hypercalciuria in Beckwith-Wiedemann syndrome. J Pediatr 142:206–208PubMedCrossRef Goldman M, Shuman C, Weksberg R, Rosenblum ND (2003) Hypercalciuria in Beckwith-Wiedemann syndrome. J Pediatr 142:206–208PubMedCrossRef
14.
Zurück zum Zitat Goldman M, Smith A, Shuman C, Caluseriu O, Wei C, Steele L, Ray P, Sadowski P, Squire J, Weksberg R, Rosenblum ND (2002) Renal abnormalities in Beckwith-Wiedemann syndrome are associated with 11p15.5 uniparental disomy. J Am Soc Nephrol 13:2077–2084PubMedCrossRef Goldman M, Smith A, Shuman C, Caluseriu O, Wei C, Steele L, Ray P, Sadowski P, Squire J, Weksberg R, Rosenblum ND (2002) Renal abnormalities in Beckwith-Wiedemann syndrome are associated with 11p15.5 uniparental disomy. J Am Soc Nephrol 13:2077–2084PubMedCrossRef
15.
Zurück zum Zitat Wong CA, Cuda S, Kirsch A (2011) A review of the urologic manifestations of Beckwith-Wiedemann syndrome. J Pediatr Urol 7:140–144PubMedCrossRef Wong CA, Cuda S, Kirsch A (2011) A review of the urologic manifestations of Beckwith-Wiedemann syndrome. J Pediatr Urol 7:140–144PubMedCrossRef
16.
Zurück zum Zitat Ortiz-Neira CL, Traubici J, Alan D, Moineddin R, Shuman C, Weksberg R, Epelman M (2009) Sonographic assessment of renal growth in patients with Beckwith-Wiedemann syndrome: the Beckwith-Wiedemann syndrome renal nomogram. Clinics (Sao Paulo) 64:41–44CrossRef Ortiz-Neira CL, Traubici J, Alan D, Moineddin R, Shuman C, Weksberg R, Epelman M (2009) Sonographic assessment of renal growth in patients with Beckwith-Wiedemann syndrome: the Beckwith-Wiedemann syndrome renal nomogram. Clinics (Sao Paulo) 64:41–44CrossRef
17.
Zurück zum Zitat Priolo M, Sparago A, Mammì C, Cerrato F, Laganà C, Riccio A (2008) MS-MLPA is a specific and sensitive technique for detecting all chromosome 11p15.5 imprinting defects of BWS and SRS in a single-tube experiment. Eur J Hum Genet 16:565–571PubMedCrossRef Priolo M, Sparago A, Mammì C, Cerrato F, Laganà C, Riccio A (2008) MS-MLPA is a specific and sensitive technique for detecting all chromosome 11p15.5 imprinting defects of BWS and SRS in a single-tube experiment. Eur J Hum Genet 16:565–571PubMedCrossRef
18.
Zurück zum Zitat Romanelli V, Belinchón A, Benito-Sanz S, Martínez-Glez V, Gracia-Bouthelier R, Heath KE, Campos-Barros A, García-Miñaur S, Fernandez L, Meneses H, López-Siguero JP, Guillén-Navarro E, Gómez-Puertas P, Wesselink JJ, Mercado G, Esteban-Marfil V, Palomo R, Mena R, Sánchez A, Del Campo M, Lapunzina P (2010) CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet A 152:1390–1397 Romanelli V, Belinchón A, Benito-Sanz S, Martínez-Glez V, Gracia-Bouthelier R, Heath KE, Campos-Barros A, García-Miñaur S, Fernandez L, Meneses H, López-Siguero JP, Guillén-Navarro E, Gómez-Puertas P, Wesselink JJ, Mercado G, Esteban-Marfil V, Palomo R, Mena R, Sánchez A, Del Campo M, Lapunzina P (2010) CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet A 152:1390–1397
19.
Zurück zum Zitat Weksberg R, Shuman C, Beckwith JB (2010) Beckwith-Wiedemann syndrome. Eur J Hum Genet 18:8–14PubMedCrossRef Weksberg R, Shuman C, Beckwith JB (2010) Beckwith-Wiedemann syndrome. Eur J Hum Genet 18:8–14PubMedCrossRef
20.
Zurück zum Zitat Rosenbaum DM, Korngold E, Teele RL (1984) Sonographic assessment of renal length in normal children. AJR Am J Roentgenol 142:467–469PubMed Rosenbaum DM, Korngold E, Teele RL (1984) Sonographic assessment of renal length in normal children. AJR Am J Roentgenol 142:467–469PubMed
21.
Zurück zum Zitat Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC, Riccio A (2004) Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat Genet 36:958–960PubMedCrossRef Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC, Riccio A (2004) Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat Genet 36:958–960PubMedCrossRef
22.
Zurück zum Zitat Shah K (1983) Beckwith-Wiedemann syndrome: role of ultrasound in its management. Clin Radiol 34:313–319PubMedCrossRef Shah K (1983) Beckwith-Wiedemann syndrome: role of ultrasound in its management. Clin Radiol 34:313–319PubMedCrossRef
23.
Zurück zum Zitat Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD (1986) Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet 74:143–154PubMedCrossRef Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD (1986) Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet 74:143–154PubMedCrossRef
24.
Zurück zum Zitat Elliott M, Bayly R, Cole T, Temple IK, Maher ER (1994) Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clin Genet 46:168–174PubMedCrossRef Elliott M, Bayly R, Cole T, Temple IK, Maher ER (1994) Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clin Genet 46:168–174PubMedCrossRef
25.
Zurück zum Zitat Hunter AG, Allanson JE (1994) Follow-up study of patients with Wiedemann-Beckwith syndrome with emphasis on the change in facial appearance over time. Am J Med Genet 51:102–107PubMedCrossRef Hunter AG, Allanson JE (1994) Follow-up study of patients with Wiedemann-Beckwith syndrome with emphasis on the change in facial appearance over time. Am J Med Genet 51:102–107PubMedCrossRef
26.
Zurück zum Zitat Moore ES, Ward RE, Escobar LF, Carlin ME (2000) Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence. Am J Med Genet 90:283–290PubMedCrossRef Moore ES, Ward RE, Escobar LF, Carlin ME (2000) Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence. Am J Med Genet 90:283–290PubMedCrossRef
27.
Zurück zum Zitat Beckwith JB, Kiviat NB, Bonadio JF (1990) Nephrogenic rests, nephroblastomatosis and the pathogenesis of Wilms’ tumor. Pediatr Pathol 10:1–36PubMedCrossRef Beckwith JB, Kiviat NB, Bonadio JF (1990) Nephrogenic rests, nephroblastomatosis and the pathogenesis of Wilms’ tumor. Pediatr Pathol 10:1–36PubMedCrossRef
28.
Zurück zum Zitat Russo S, Finelli P, Recalcati MP, Ferraiuolo S, Cogliati F, Dalla Bernardina B, Tibiletti MG, Agosti M, Sala M, Bonati MT, Larizza L (2006) Molecular and genomic characterization of cryptic chromosomal alterations leading to paternal duplication of the 11p15.5 Beckwith-Wiedemann region. J Med Genet 43:3929CrossRef Russo S, Finelli P, Recalcati MP, Ferraiuolo S, Cogliati F, Dalla Bernardina B, Tibiletti MG, Agosti M, Sala M, Bonati MT, Larizza L (2006) Molecular and genomic characterization of cryptic chromosomal alterations leading to paternal duplication of the 11p15.5 Beckwith-Wiedemann region. J Med Genet 43:3929CrossRef
29.
Zurück zum Zitat Kulkarni R, Wolf JS Jr, Padiyar N, Zuckerman L, Gera R, Scott-Emuakpor AB (2002) Severe intrarenal fibrosis, infundibular stenosis, renal cysts, and persistent perilobar nephrogenic rests in a patient with Beckwith-Wiedemann syndrome 27 years after diffuse nephroblastomatosis and Wilms tumor: natural progression or a consequence of treatment? J Pediatr Hematol Oncol 24:389–393PubMedCrossRef Kulkarni R, Wolf JS Jr, Padiyar N, Zuckerman L, Gera R, Scott-Emuakpor AB (2002) Severe intrarenal fibrosis, infundibular stenosis, renal cysts, and persistent perilobar nephrogenic rests in a patient with Beckwith-Wiedemann syndrome 27 years after diffuse nephroblastomatosis and Wilms tumor: natural progression or a consequence of treatment? J Pediatr Hematol Oncol 24:389–393PubMedCrossRef
Metadaten
Titel
Nephrological findings and genotype–phenotype correlation in Beckwith–Wiedemann syndrome
verfasst von
Alessandro Mussa
Licia Peruzzi
Nicoletta Chiesa
Agostina De Crescenzo
Silvia Russo
Daniela Melis
Luigi Tarani
Giuseppina Baldassarre
Lidia Larizza
Andrea Riccio
Margherita Silengo
Giovanni Battista Ferrero
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 3/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-011-2009-4

Weitere Artikel der Ausgabe 3/2012

Pediatric Nephrology 3/2012 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.