Phenotypic Variation in 46,XX Disorders of Sex Development due to the 4th Zinc Finger Domain Variant of WT1 : A Familial Case Report.

INTRODUCTION: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development. Recently, the variants in fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the nine patients reported were de novo, and no familial cases were identified.

CASE PRESENTATION AND RESULTS: The proband (16yrs social female), had 46,XX karyotype with dysplastic testes and moderate virilization in genitalia. A ZF4 variant, p.Arg495Gln in WT1 was identified in the proband, her brother and mother. The mother did not show any virilization with normal fertility, and the 46,XY brother developed normal puberty.

DISCUSSION/CONCLUSION: The phenotypic variations due to ZF4 variant are extremely broad in 46,XX cases.