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Frasier and Denys-Drash syndromes: different disorders or part of a spectrum?
  1. Ania Koziella,
  2. Richard Grundyb
  1. aDepartment of Molecular Medicine, Institute of Child Health, 30, Guilford Street, London WC1N, UK, bInstitute of Child Health, University of Birmingham, Whittall Street, Birmingham B4 6NH, UK
  1. Dr Grundy. email: r.g.grundy{at}bham.ac.uk

https://doi.org/10.1136/adc.81.4.365

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    Frasier and Denys-Drash syndromes are both characterised by renal disease, intersex, and a predisposition to develop tumours. The association of mutations within the Wilms’s tumour suppressor gene (WT1) and the Denys-Drash syndrome is now well described. More recently, mutations of the WT1 gene have also been found to cause Frasier syndrome. The clinical and genetic overlap between these two syndromes has opened up the debate as to whether these two conditions are part of the same spectrum or are different disorders caused by different mutations within the same gene. Molecular studies of these rare syndromes are providing valuable insights into the role of the WT1 gene in genitourinary development and underline the increasing importance of genetic analysis for diagnostic, prognostic, and therapeutic purposes.

    Clinical aspects

    The Denys-Drash syndrome1 2 consists of a triad of intersex, Wilms’s tumour, and nephrotic syndrome. In Denys-Drash syndrome, the characteristic glomerular damage causing the nephrotic syndrome manifests as diffuse mesangial sclerosis and this may be the presenting feature, either at birth or in the 1st few years of life. The presence of nephropathy is the key defining feature of the syndrome, which can exist in either a complete form, consisting of all three components of the triad,3 or an incomplete form, in which the nephropathy is present in association with either one of the other features—either Wilms’s tumour or intersex.4-6Progression of the nephropathy into renal failure is inevitable. A wide variety of genital abnormalities is seen: most patients with 46 XX appear normal, but might have streak gonads, whereas most patients with 46 XY exhibit ambiguous genitalia or male pseudohermaphroditism. Most, but not all, patients with Denys-Drash syndrome develop Wilms’s tumour, the median age at presentation is 18 months, with 20% of cases being bilateral5 6—classic features of a Wilms’s tumour …

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