ESPN 50th Annual Meeting

ESPN 2017


 
Congenital nephrotic syndrome: a novel non-pathogenic intragenic deletion of Wt1 with development of Wilms Tumour: c.[643-6C>A];[(=)]
VICTORIA HARKINS 1 HEATHER MAXWELL 1 IAN RAMAGE 1

1- NHS GREATER GLASGOW AND CLYDE
 
Introduction:

Mutations in the WT1 gene are associated with Congenital Nephrotic Syndrome (CNS) and Wilms Tumour. We present a female infant who presented at age 4 months markedly oedematous, hypoalbuminaemic and with nephrotic range proteinuria. Immediate initial management consisted of haemofiltration and albumin replacement with subsequent therapy consisting of regular albumin infusions and iatrogenic reduction in GFR with ACE inhibition and NSAID therapy. 

Material and methods:

A diagnosis of CNS was made clinically with an initial PCR of >7000mg/mmol in the presence of oedema and hypoalbuminemia. Genetic analysis did not identify a known causal genotype, however a likely non pathogenic Wt1 mutation class 2 was identified c.[643-6C>A];[(=)]. The mutation was rediscussed with the primary analyst and local geneticist due to concerns of risk of developing Wilms Tumour and the need for subsequent USS monitoring. On rediscussion it was still felt to be likely non-pathogenic as no previous intragenic deletions of Wt1 have previously been found to be pathogenic.

Results:

At 11 months of age she underwent bilateral nephrectomy due to ongoing hypertension despite maximal medical management resulting in PRES.  At resection a left renal mass was noted arising from the anterior surface of the medial aspect of the left kidney. Pathology revealed an incompletely excised stage III Wilms Tumour with capsular spread and spread to the perinephric tract. There was no metastatic spread on full body imaging and she underwent an 11 day course of radiotherapy and 28 weeks of chemotherapy of Vincrsitine, Actinomycin and Doxorubicin. 

Conclusions:

The identification of pathogenic mutations in the Wt1 gene are crucial in identifying patients at risk of developing Wilms Tumour with requirement of ongoing ultrasound surveillance. We report a case of congenital nephrotic syndrome and Wilms Tumour with mutation c.[643-6C>A];[(=)] that phenotypically may be significant in our patient and we are not aware of intragenic deletions reported as pathogenic elsewhere in the literature.