Johns Hopkins Division of Infectious Diseases
M E N S  H E A L T H  G U I D E

Men's Health Sponsors About this site Site Map
Expert Questions & AnswersFeature Articles
  Partial Gonadal Dysgenesis
Authors: Claude Migeon, M.D., Amy Wisniewski, Ph.D. Last modified: October 11, 2001


  • Gonadal Dysgenesis (GD) refers to the condition in which the gonads do not develop normally during fetal life.
  • Early in fetal life several transcription factors (such as LIM-1, SOX-9, SF-1, DAX-1 and WT-1) are necessary for gonads formation.
  • The SRY gene is also needed for testes formation. Mutations of SRY or any of the factors mentioned above will result in GD. DAX-1 gene duplication also results in GD.
  • GD in 46,XY individuals exists in both complete (CGD or Swyer Syndrome) and partial (PGD) forms.
  • Characteristically, GD impairs the two main functions of the testes: secretion of testosterone by Leydig cells and Mullerian Inhibiting Substance (MIS) by Sertoli cells.
  • Decreased testosterone secretion results in under-masculinization of the external genitalia and poor development of male ducts.
  • Decreased MIS secretion results in the failure to suppress female duct development.


  • Presence of a uterus and utriculo-vaginal pouch in patients reared male.
  • Gonadal tumors.
  • SF-1 mutations can result in adrenal insufficiency and CNS abnormalities.
  • WT-1 mutations are associated with Wilms tumors.
  • SOX-9 mutations are associated with camptomelic dysplasia.
  • DAX-1 mutations are associated with adrenal insufficiency and hypogonadotropic hypogonadism.
  • Turner stigmata in cases with hidden 45,XO/46,XY mosaicism.


  • At birth, infants present with varying degrees of under-masculinized genitalia (ranging from almost completely female to almost completely male).
  • In patients reared male, a small penis with cryptochordism or small testes.
  • Infertility.


  • At birth a full work-up for ambiguous genitalia must be obtained.
  • Monitor electrolytes daily.
  • At Day 1 or 2 of life, obtain a karyotype, plasma androstenedione, testosterone and dihydrotestosterone.
  • At Day 3 or 4, measure plasma 17-hydroxyprogesterone and 17-hydroxypregnenolone.
  • At Day 5, obtain a genitogram.
  • At Day 6 to 7, measure MIS and obtain blood for DNA studies.
  • At Day 8 to 9, repeat androstenedione, testosterone, dihydrotestosterone and 17-hydroxyprogesterone.
  • If the karyotype is 46,XY, Mullerian structures are seen on the genitogram and androstendione, testosterone, dihydrotestosterone and MIS are low, a presumptive diagnosis of GD can be made.
  • Both 17-hydroxyprogesterone and 17-hydroxypregnenolone should be normal except in cases of SF-1 or DAX-1 mutations.
  • Once a presumptive diagnosis of GD has been made, this can be confirmed by DNA studies. However these are difficult to have done and the exact mutation cannot always be identified.
  • Congenital Adrenal Hyperplasia (CAH) due to 3B-hydroxysteroid dehydrogenase deficiency
  • 5alpha-reductase deficiency
  • Partial Androgen Insensitivity Syndrome (PAIS)
  • Steroidogenic enzyme defect associated with testosterone production
  • Leydig cell hypoplasia
  • Timing defect
  • True hermaphroditism


  • 46,XY karyotype
  • Androstendione, testosterone and dihydrotestosterone concentrations are below normal.
  • MIS concentration is below normal.
  • 17-hydroxyprogesterone and 17-hydroxypregnenolone concentrations are decreased in cases of SF-1 and DAX-1 mutations.
  • A genitogram reveals the presence of Mullerian structures such as a uterus or utriculo-vaginal pouch.
  • At birth, consideration for raising the infant as female is made if the stretched penile length is equal to or less than 1.9 cm (mean - 2.5 SDs) and perineo-scrotal hypospadias exists.
  • If a uterus is present female rearing is considered because in such cases pregnancy is possible with invitro fertilization.
  • In less severe cases of genital ambiguity, male rearing can be successful.
  • When deciding on sex of rearing, parents must be completely informed about sex differentiation and abnormalities that can occur (
  • Parents and patients should have realistic expectations for the difficulties and outcome of medical and surgical treatments offered to them regardless of sex of rearing.
  • Patients with PGD reared male do not produce adequate amounts of testicular androgens. Testosterone treatment is needed to optimize masculinization.
  • Under-masculinized genitalia requires surgical correction for hypospadias and removal of the utriculo-vaginal pouch.
  • If a uterus or other Mullerian structures are present, a hysterectomy is required.
  • If the testes were removed due to the inability to correct cryptochordism or gonadal tumor, implantation of prosthetic testes is recommended.
  • Patients benefit greatly from education and counseling regarding their condition. Education allows for patients and parents to make informed medical and surgical choices.
  • Many men and women with PGD benefit from counseling when dealing with infertility, sexual dysfunction and genital surgery.
  • It is important that people affected by PGD seek medical, surgical and psychological care from those who have experience treating this condition.
  • In patients with marked genital ambiguity, female sex of rearing may be optimal. This is particularly true in individuals with a well-formed uterus as they can carry pregnancies.
  1. Migeon CJ, Wisniewski AB and Gearhart JP ;  Syndrome of Abnormal Sex Differentiation: A Guide for Patients and Their Families ;

    This online guide explains gonadal dysgenesis (GD) within the context of male sex differentiation.

  2. Berkovitz GD, Fechner PY, Zacur HW et al ;  Clinical and Pathologic Spectrum of 46,XY Gonadal Dysgenesis: Its Relevance to the Understanding of Sex Differentiation. ;  Medicine; 70:375, 1991.

  3. Nachtigal MW, Hirokawa Y, Enyeart-Van Houten DL et al ;  Wilms tumor 1 and DAX-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. ;  Cell; 93:445, 1998.

  4. Koopman P ;  Sry and Sox-9: Mammalian testis-determining genes. ;  Cell Mol Life Sci; 55:839, 1999.

Copyright © 2002 The Johns Hopkins University School of Medicine. All rights reserved.