Clinical Guidance

WT1 disorder is characterized by congenital/infantile or childhood onset of a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or mllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT), gonadoblastoma, and 46,XX gonadal dysgenesis . In adulthood, most individuals are affected by early gonadal insufficiency of variable severity with potential impact on puberty and fertility.

Source: GeneReviews — "WT1 Disorder"

Penetrance

The penetrance of WT1 disorder is high. It is age dependent, reaching about 90% by the end of puberty. A few asymptomatic parents heterozygous for the same germline WT1 variant in their affected offspring have been reported [, , , , ]. The penetrance appears to depend on the sex of the affected parent, with higher penetrance associated with paternal origin of the WT1 variant . However, current data on penetrance are limited because the variable expressivity of WT1 pathogenic variants was not recognized until recently, and the asymptomatic parents of a child with a WT1 pathogenic variant were not routinely tested.

Source: GeneReviews — "WT1 Disorder"

Differential Diagnosis

For the differential diagnosis of:

• Steroid-resistant nephrotic syndrome, see Genetic Steroid-Resistant Nephrotic Syndrome Overview;

• Wilms tumor, see Wilms Tumor Predisposition;

• 46,XY disorders of testicular development, see Nonsyndromic Disorders of Testicular Development Overview;

• Diaphragmatic hernia, see

Source: GeneReviews — "WT1 Disorder"

Clinical Guidance

Avoid treating glomerulopathy with immunosuppressants, as they are not effective and potentially toxic.

Source: GeneReviews — "WT1 Disorder"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "WT1 Disorder"