Pediatric Nephrology

, Volume 21, Issue 12, pp 1909–1912 | Cite as

Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect

  • Hee Yeon Cho
  • Byong Sop Lee
  • Chang Hyun Kang
  • Woong-Han Kim
  • Il Soo Ha
  • Hae Il CheongEmail author
  • Young Choi
Brief Report


The Wilms tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and the gonads, and clinical syndromes associated with WT1 mutations, such as WAGR syndrome, Denys-Drash syndrome and Frasier syndrome, typically manifest as renal and genitourinary abnormalities. WT1 may also play an important role in the development of the diaphragm, and recently several papers have reported an association between WT1 mutations and diaphragmatic hernias. In addition, WT1 mutations were also detected in some patients with Meacham syndrome, a rare malformation syndrome comprising congenital diaphragmatic hernia, double vagina, sex reversal, and cardiac malformations. Here, we report a case of an infant with typical clinical features of Deny-Drash syndrome and a heterozygous missense mutation, Arg366His, in the WT1 gene, in whom a diaphragm defect was detected after starting peritoneal dialysis. Diaphragmatic defects are rare but may be considered as clinical manifestations of WT1 mutation syndromes. In addition, we suggest that WT1 abnormalities should be suspected in patients with chronic renal failure who develop hydrothorax after peritoneal dialysis, especially in those with genitourinary abnormalities.


WT1 Denys-Drash syndrome Diaphragmatic defect Meacham syndrome 



This study was supported by a grant (04-2005-064-0) from the Seoul National University Hospital Research Fund.


  1. 1.
    Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB (1992) The expression of the Wilms’ tumour gene, WT1, in the developing mammalian embryo. Mech Dev 40:85–97CrossRefGoogle Scholar
  2. 2.
    Pritchard- Jones K, Fleming S, Davidson D, Bickmore W, Porteus D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D (1990) The candidate Wilms’ tumor gene is involved in genitourinary development. Nature 346:194–197CrossRefGoogle Scholar
  3. 3.
    Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691CrossRefGoogle Scholar
  4. 4.
    Bruening W, Bardeesy N, Silverman BL, Cohn RA, Machin GA, Aronson AJ, Housman D, Pelletier J (1992) Germline intronic and exonic mutations in the Wilms’ tumour gene (WT1) affecting urogenital development. Nat Genet 1:144–148CrossRefGoogle Scholar
  5. 5.
    Little M, Wells C (1997) A clinical overview of WT1 gene mutations. Hum Mutat 9:209–225CrossRefGoogle Scholar
  6. 6.
    Baird PN, Santos A, Groves N, Jadresic L, Cowell JK (1992) Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. Hum Mol Genet 1:301–305CrossRefGoogle Scholar
  7. 7.
    Barbaux S, Niaudet P, Gubler M-C, Grunfeld J-P, Jaubert F, Kuttenn F, Fekete CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K (1997) Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17:467–470CrossRefGoogle Scholar
  8. 8.
    Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M (2005) WAGR syndrome: a clinical review of 54 cases. Pediatrics 116:984–988CrossRefGoogle Scholar
  9. 9.
    Scott DA, Cooper ML, Stankiewicz P, Patel A, Potocki L, Cheung SW (2005) Congenital diaphragmatic hernia in WAGR syndrome. Am J Med Genet A134:430–433CrossRefGoogle Scholar
  10. 10.
    Gustavson K-H, Anneren G, Wranne L (1984) Two cases of 11p13 interstitial deletion and unusual clinical features. Clin Genet 26:247–249CrossRefGoogle Scholar
  11. 11.
    Devriendt K, Deloof E, Moerman P, Legius E, Vanhole C, de Zegher F, Proesmans W, Devlieger H (1995) Diaphragmatic hernia in Denys-Drash syndrome. Am J Med Genet 57:97–101CrossRefGoogle Scholar
  12. 12.
    Denamur E, Bacquet N, Baudouin V, Da Silva F, Veitia R, Peuchmaur M, Elion J, Gubler MC, Fellous M, Niaudet P, Loirat C (2000) WT1 splice-site mutations are rarely associated with primary steroid-resistant focal and segmental glomerulosclerosis. Kidney Int 57:1868–1872CrossRefGoogle Scholar
  13. 13.
    Klaassens M, van Dooren M, Eussen HJ, Douben H, den Dekker AT, Lee C, Donahoe PK, Galjaard RJ, Goemaere N, de Krijger RR, Wouters C, Wauters J, Oostra BA, Tibboel D, de Klein A (2005) Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization. Am J Hum Genet 76:877–882CrossRefGoogle Scholar
  14. 14.
    Pober BR, Lin A, Russell M, Ackerman KG, Chakravorty S, Strauss B, Westgate MN, Wilson J, Donahoe PK, Holmes LB (2005) Infants with Bochdalek diaphragmatic hernia: sibling precurrence and monozygotic twin discordance in a hospital-based malformation surveillance program. Am J Med Genet A138:81–88CrossRefGoogle Scholar
  15. 15.
    Reardon W, Smith S, Suri M, Grant J, O’Neill D, Kelehan D, Fitzpatrick D, Hastie ND (2004) WT1 mutation is a cause of congenital diaphragmatic hernia associated with Meacham syndrome. Presented at the annual meeting of the American Society of Human Genetics, October 26–30, 2004. Toronto, OntarioGoogle Scholar
  16. 16.
    Meacham LR, Winn KJ, Culler FL, Parks JS (1991) Double vagina, cardiac, pulmonary, and other genital malformations with 46,XY karyotype. Am J Med Genet 41:478–481CrossRefGoogle Scholar
  17. 17.
    Toriello HV, Higgins JV (1991) Report of another child with sex reversal and cardiac, pulmonary, and diaphragm defects. Am J Med Genet 44:252 (Letter)CrossRefGoogle Scholar
  18. 18.
    Masswinkel-Mooji PD, Stokvis-Brantsma WH (1992) Phenotypically normal girl with male pseudohermaphroditism, hypoplastic left ventricle, lung aplasia, horseshoe kidney, and diaphragmatic hernia. Am J Med Genet 42:647–648CrossRefGoogle Scholar
  19. 19.
    Killeen OG, Kelehan P, Reardon W (2002) Double vagina with sex reversal, congenital diaphragmatic hernia, pulmonary and cardiac malformations—another case of Meacham syndrome. Clin Dysmorphol 11:25–28CrossRefGoogle Scholar
  20. 20.
    Park S, Schalling M, Bernard A, Maheswaran S, Shipley GC, Roberts D, Fletcher J, Shipman R, Rheinwald J, Demetri G, Griffin J, Minden M, Housman DE, Haber DA (1993) The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma. Nat Genet 4:415–420CrossRefGoogle Scholar
  21. 21.
    Ordóñez NG (2005) Immunohistochemical diagnosis of epithelioid mesothelioma. An update. Arch Pathol Lab Med 129:1407–1414PubMedGoogle Scholar
  22. 22.
    Nordenskjöld A, Tapper-Persson M, Anvret M (1996) No evidence of WT1 gene mutations in children with congenital diaphragmatic hernia. J Pediatr Surg 31:925–927CrossRefGoogle Scholar
  23. 23.
    Dharnidharka VR, Ruteshouser EC, Rosen S, Kozakewich H, Harris HW Jr, Herrin JT, Huff V (2001) Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins. Pediatr Nephrol 16:227–231CrossRefGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  • Hee Yeon Cho
    • 1
  • Byong Sop Lee
    • 1
  • Chang Hyun Kang
    • 2
  • Woong-Han Kim
    • 2
  • Il Soo Ha
    • 1
  • Hae Il Cheong
    • 1
    Email author
  • Young Choi
    • 1
  1. 1.Department of PediatricsSeoul National University Children’s HospitalSeoulSouth Korea
  2. 2.Department of Thoracic and Cardiovascular SurgerySeoul National University HospitalSeoulSouth Korea

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