Table 3. [Other Allelic Syndromic Disorders]. - GeneReviews®

Gene	Condition	Molecular Pathogenesis	Clinical Characteristics
SOX3	Panhypopituitarism, X-linked (OMIM 312000)	Duplication or expansion of polyalanine tract	Panhypopituitarism has been described in a few 46,XY persons w/SOX3 duplications (their heterozygous 46,XX mothers were not affected).
SOX9	Campomelic dysplasia (CD) ¹	Heterozygous loss-of-function variant	Skeletal dysplasia; distinctive facies; Pierre Robin sequence w/cleft palate; shortening & bowing of long bones; clubfeet Many affected infants die in neonatal period due to laryngotracheomalacia & respiratory compromise Ambiguous genitalia or typical female external genitalia are seen in most XY persons. DSD is not a feature of 46,XX persons w/CD.
WT1	Denys-Drash syndrome (See WT1 Disorder.) ²	Heterozygous variants in exons 8 or 9 encoding ZF2 & ZF3 domains	In Denys-Drash & Frasier syndromes, 46,XY children typically present w/ambiguous or female external genitalia, gonadal dysgenesis, nephrotic syndrome, Wilms tumor &/or gonadoblastoma.
Frasier syndrome (See WT1 Disorder.) ²	Heterozygous splice site variants
Meacham syndrome (See WT1 Disorder.) ²	Mutational spectrum overlap w/Denys-Drash syndrome	Meacham syndrome is assoc w/congenital diaphragmatic hernia, congenital heart disease, & retention of & anomalies in müllerian structures.
WAGR syndrome (See PAX6-Related Aniridia.) ²	Contiguous gene syndrome due to haploinsufficiency of WT1, PAX6, & other genes	WAGR syndrome incls Wilms tumors, aniridia, genitourinary anomalies, & DD.
Isolated nephrotic syndrome (See WT1 Disorder.) ²	Mutational spectrum overlap w/Denys-Drash syndrome

Gene

Condition

Molecular Pathogenesis

Clinical Characteristics

SOX3

Panhypopituitarism, X-linked (OMIM 312000)

Duplication or expansion of polyalanine tract

Panhypopituitarism has been described in a few 46,XY persons w/SOX3 duplications (their heterozygous 46,XX mothers were not affected).

SOX9

Campomelic dysplasia (CD) ¹

Heterozygous loss-of-function variant

Skeletal dysplasia; distinctive facies; Pierre Robin sequence w/cleft palate; shortening & bowing of long bones; clubfeet
Many affected infants die in neonatal period due to laryngotracheomalacia & respiratory compromise
Ambiguous genitalia or typical female external genitalia are seen in most XY persons. DSD is not a feature of 46,XX persons w/CD.

WT1

Denys-Drash syndrome (See WT1 Disorder.) ²

Heterozygous variants in exons 8 or 9 encoding ZF2 & ZF3 domains

In Denys-Drash & Frasier syndromes, 46,XY children typically present w/ambiguous or female external genitalia, gonadal dysgenesis, nephrotic syndrome, Wilms tumor &/or gonadoblastoma.

Frasier syndrome (See WT1 Disorder.) ²

Heterozygous splice site variants

Meacham syndrome (See WT1 Disorder.) ²

Mutational spectrum overlap w/Denys-Drash syndrome

Meacham syndrome is assoc w/congenital diaphragmatic hernia, congenital heart disease, & retention of & anomalies in müllerian structures.

WAGR syndrome (See PAX6-Related Aniridia.) ²

Contiguous gene syndrome due to haploinsufficiency of WT1, PAX6, & other genes

WAGR syndrome incls Wilms tumors, aniridia, genitourinary anomalies, & DD.

Isolated nephrotic syndrome (See WT1 Disorder.) ²

Mutational spectrum overlap w/Denys-Drash syndrome

From: Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.