Nephromegaly in Infancy and Early Childhood: A Risk Factor for Wilms Tumor in Beckwith-Wiedemann Syndrome

DeBaun, Michael R.; Siegel, M J; Choyke, Peter L.

doi:10.1016/s0022-5347(01)62647-8

Cited by 10 publications

(17 citation statements)

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“…The overall risk for tumor development in children with BWS is approximately 7.5% [Wiedemann, 1983] but it appears that a number of factors may influence this risk figure, including the presence of hemihyperplasia [Wiedemann, 1983], nephromegaly [DeBaun et al, 1998], and nephrogenic rests or nephroblastomatosis [Coppes et al, 1999]. In addition, the specific…”

Section: Clinical Managementmentioning

confidence: 99%

Beckwith–Wiedemann syndrome

Weksberg

Shuman²,

Smith

2005

American J of Med Genetics Pt C

270

201

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Beckwith-Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome associated with an increased risk for embryonal tumor development. BWS provides an ideal model system to study epigenetic mechanisms. This condition is caused by a variety of genetic or epigenetic alterations within two domains of imprinted growth regulatory genes on human chromosome 11p15. Molecular studies of BWS have provided important data with respect to epigenotype/genotype-phenotype correlations; for example, alterations of Domain 1 are associated with the highest risk for tumor development, specifically Wilms' tumor. Further, the elucidation of the molecular basis for monozygotic twinning in BWS defined a critical period for imprint maintenance during pre-implantation embryonic development. In the future, such molecular studies in BWS will permit enhanced medical management and targeted genetic counseling.

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Section: Clinical Managementmentioning

confidence: 99%

Beckwith–Wiedemann syndrome

Weksberg

Shuman²,

Smith

2005

American J of Med Genetics Pt C

270

201

View full text Add to dashboard Cite

show abstract

“…10 At a clinical level, it appears that those with documented nephromegaly in the first year of life are most at risk. 11 However, before it can be advised that subgroups might be identifiable in which the risk of Wilms' tumours is extremely low, this requires prospective evaluation. A registry of BWS patients and their tumours is maintained by Dr DeBaun in the USA and may provide information on this point in the future.…”

Section: Geneticsmentioning

confidence: 99%

Controversies and advances in the management of Wilms' tumour

Pritchard‐Jones

2002

Archives of Disease in Childhood

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“…In this series, tumors were diagnosed for 22 of 159 patients (14%), including hepatoblastomas in seven cases, adrenal carcinoma in one, rhabdomyosarcoma in one, and Wilms' tumor in 13 (8% of all patients). The risk of Wilms' tumor in BWS is significantly increased among patients with hemihyperplasia and/or nephromegaly (1,18,20). Previous studies demonstrated that hemihyperplasia occurs in approximately 25% of BWS cases (2).…”

Section: Renal Abnormalities Among Patients With Bwsmentioning

confidence: 99%

Renal Abnormalities in Beckwith-Wiedemann Syndrome Are Associated with 11p15.5 Uniparental Disomy

Goldman¹,

Smith²,

Shuman³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. Beckwith-Wiedemann syndrome (BWS) is a somatic overgrowth syndrome characterized by a variable incidence of congenital anomalies, including hemihyperplasia and renal malformations. BWS is associated with disruption of genomic imprinting and/or mutations in one or more genes encoded on 11p15.5, including CDKN1C (p57 KIP2 ). It was hypothesized that genotypic and epigenotypic abnormalities of the 11p15.5 region affecting CDKN1C were associated with renal abnormalities. Medical records for 159 individuals with BWS were reviewed. All underwent at least one abdominal ultrasonographic evaluation. Testing for paternal uniparental disomy (UPD) at 11p15.5, CDKN1C mutations, and imprinting defects at KvDMR1 was performed for 96, 32, and 47 patients, respectively. Of the 159 patients, 67 (42%) exhibited renal abnormalities, mainly nephromegaly (25%), collecting system abnormalities (11%), and renal cysts (10.5%). The frequency of renal lesions among patients who were tested for genetic abnormalities did not differ from that among patients who were not tested. Paternal UPD was demonstrated in 22 of 96 cases (23%), CDKN1C mutations in eight of 32 cases (25%), and KvDMR1 imprinting defects in 21 of 47 cases (45%). The 22 UPD-positive patients exhibited a significantly higher incidence of renal abnormalities (P ϭ 0.0026). Surprisingly, the eight patients with CDKN1C mutations exhibited no significant increase in the incidence of renal lesions (P ϭ 0.29). Imprinting defects at KvDMR1, which might downregulate CDKN1C, were also not associated with a significant difference in the incidence of renal disease. Whereas UPD at 11p15.5 in BWS was associated with a higher incidence of renal abnormalities, mutations at CDKN1C and KvDMR1 imprinting defects were not, suggesting that imprinted genes on 11p15.5 other than CDKN1C are critical for renal development.Beckwith-Wiedemann syndrome (BWS) is a congenital disorder characterized by somatic overgrowth, macroglossia, anterior abdominal wall defects, and macrosomia. Additional but variable features include a typical facial appearance, ear lobe creases or pits, facial nevus flammeus, hemihyperplasia, neonatal hypoglycemia, organomegaly, genitourinary abnormalities, and a predisposition to develop embryonal tumors (1,2). Renal abnormalities have been observed in up to 59% (range, 25 to 59%) of patients with BWS (2-4). The most common renal abnormalities are nephromegaly (19 to 59%), simple cysts (13 to 19%), hydronephrosis (12 to 14%), and medullary cysts (5 to 13%). Other, less common findings include nephrocalcinosis (with or without nephrolithiasis) (4%), increased cortical and pyramidal echogenicity (4%), a double collecting system (4%), and caliceal diverticula (1.3%). The molecular mechanisms causing these renal abnormalities are undefined.BWS is associated with disruption of genomic imprinting of one or more genes in the 11p15.5 region. Genomic imprinting is a process that results in parent-of-origin-specific gene expression. Approximately 20% of sporadic BWS cases demonstr...

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Nephromegaly in Infancy and Early Childhood: A Risk Factor for Wilms Tumor in Beckwith-Wiedemann Syndrome

Cited by 10 publications

References 0 publications

Beckwith–Wiedemann syndrome

Beckwith–Wiedemann syndrome

Controversies and advances in the management of Wilms' tumour

Renal Abnormalities in Beckwith-Wiedemann Syndrome Are Associated with 11p15.5 Uniparental Disomy

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