Frasier syndrome

Frasier syndrome is a urogenital disorder associated with the WT1, or Wilms tumor 1, gene, first documented in 1964, and its presentation differs by chromosomal sex. In individuals with XX chromosomes it typically causes progressive kidney disease that may not appear until childhood or adolescence and is often first diagnosed as isolated nephrotic syndrome, while in individuals with XY chromosomes it produces an intersex presentation in which, despite a typical male chromosome pattern, the gonads fail to develop properly into nonfunctional streak gonads carrying an increased cancer risk that usually requires surgical removal, along with ambiguous or female-appearing external genitalia. Across both presentations the disease causes progressive kidney disease from focal segmental glomerulosclerosis and an elevated risk of genitourinary tumors, particularly gonadoblastoma. It results from mutations in the WT1 gene on chromosome 11, mainly affecting intron 9 and disrupting the normal balance of WT1 protein variants, inherited in an autosomal dominant pattern though often arising as a new mutation with no family history.