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Journal of Indian Association of Pediatric Surgeons
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LETTER TO THE EDITOR
Year : 2015  |  Volume : 20  |  Issue : 4  |  Page : 197-198
 

Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6


Department of Urology and Renal Transplantation, Smt. Gulabben Rasiklal Doshi and Smt. Kamlaben Mafatlal Mehta Institute of Kidney Diseases and Research Centre & Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India

Date of Web Publication2-Sep-2015

Correspondence Address:
Dr. Jayesh Modi
2, Kamdhenu Apt., Behind St., Xaviers Loyolla Hall School, Memnagar, Ahmedabad - 380 052, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9261.154641

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How to cite this article:
Modi J, Modi P, Pal B, Kumar S. Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6. J Indian Assoc Pediatr Surg 2015;20:197-8

How to cite this URL:
Modi J, Modi P, Pal B, Kumar S. Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6. J Indian Assoc Pediatr Surg [serial online] 2015 [cited 2019 Nov 11];20:197-8. Available from: http://www.jiaps.com/text.asp?2015/20/4/197/154641


Sir,

Denys-Drash syndrome (DDS) is a rare disease consisting of the triad of Wilms' tumor, ambiguous genitalia and nephropathy. We present a rare type of mutation of WT1 gene in an infant with DDS.

An 8-month-old male child was brought to us for swelling of the abdomen and failure to thrive associated with decreased activity since 1-month. On examination, the child was dehydrated with bilateral palpable renal lumps; bilateral cryptorchidism and penoscrotal hypospadias [Figure 1]a and b. His routine blood investigations were normal except hemoglobin 8.3 g/dl and 1 + proteinuria in urinalysis. Ultrasound and computed tomography abdomen revealed bilateral well defined, heterogeneously enhancing mass lesions; 10.7 cm × 8.5 cm × 7.2 cm arising from the right kidney and 10 cm × 8 cm × 6.3 cm from the left kidney [Figure 1]c. Ultrasound guided percutaneous tru-cut biopsy was taken from both renal masses and normal renal parenchyma.
Figure 1: (a-c) Bilateral renal lumps in an 8-month-old malnourished infant with penoscrotal type of hypospadias with empty scrotum. Image of computed tomography scan shows bilateral well defined, heterogeneously enhancing masses from both kidneys


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The histopathological examination from both renal masses was showing triphasic pattern of classic Wilms' tumor with predominant blastema component. The biopsy from normal renal parenchyma showed mesangial matrix expansion with thickening of glomerular basement membrane suggestive of early nephropathy changes. His karyotype study revealed a normal 46, XY male genotype while genetic study revealed a nonsense mutation in the WT1 gene-exon 6, leading to stop codon and results in truncated proteins. The child was started on combination chemotherapy but, unfortunately, he succumbed due to sepsis with pneumonia after 14 weeks of detection of the tumor.

After Drash et al., in 1970, about 200 cases of DDS have been reported. [1],[2] Most common mutations in DDS are missense changes in exons 9 or 8, which encode for the zinc fingers 3 and 2, respectively. Exon 1-6 of the WT1 gene regulates the expression of target genes by encoding the regulatory domain. The WT1 protein mediates the morphogenesis of the kidney and gonad. Very few reports of deletions or nonsense mutations have been described which result in truncated proteins. [3] Rarely mutation of exon 6 has been described. [4] The external genitalia of male DDS varies from ambiguous genitalia to female phenotype. The proteinuria due to nephropathy, usually, starts within 2 years of age, but it may develop as late as 14 years of age. [5]

The management of DDS comprises fluid and electrolyte balance, early detection and treatment of Wilms' tumor and management of renal failure. The risk of developing Wilms' tumor in DDS is up to 50% [5] with the mean age of 1.6 years which is earlier than isolated Wilms' tumor. [6] In patients with bilateral tumors or patients with a solitary kidney with Wilms' tumor, nephron sparing surgery should be performed after neoadjuvant chemotherapy.

Our case represents that while dealing with the ambiguous genitalia with cryptorchidism, possibility of DDS should be kept in mind, and genetic study should be carried out to diagnose such rare disorder. In DDS, the risk of developing bilateral renal malignancy is high especially in early age.

 
   References Top

1.
Drash A, Sherman F, Hartmann WH, Blizzard RM. A syndrome of pseudohermaphroditism, Wilms′ tumor, hypertension, and degenerative renal disease. J Pediatr 1970;76:585-93.  Back to cited text no. 1
[PUBMED]    
2.
Mueller RF. The Denys-Drash syndrome. J Med Genet 1994;31:471-7.  Back to cited text no. 2
    
3.
Mrowka C, Schedl A. Wilms′ tumor suppressor gene WT1: From structure to renal pathophysiologic features. J Am Soc Nephrol 2000;11 Suppl 16:S106-15.  Back to cited text no. 3
    
4.
Chiang PW, Aliaga S, Travers S, Spector E, Tsai AC. Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome. Curr Opin Pediatr 2008;20:103-6.  Back to cited text no. 4
    
5.
Eddy AA, Mauer SM. Pseudohermaphroditism, glomerulopathy, and Wilms tumor (Drash syndrome): Frequency in end-stage renal failure. J Pediatr 1985;106:584-7.  Back to cited text no. 5
[PUBMED]    
6.
Montgomery BT, Kelalis PP, Blute ML, Bergstralh EJ, Beckwith JB, Norkool P, et al. Extended follow-up of bilateral Wilms tumor: Results of the National Wilms Tumor Study. J Urol 1991;146:514-8.  Back to cited text no. 6
    


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