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46,XY gonadal dysgenesis

Thursday 23 August 2007

Digital cases (digital slides)

- HPC:91 : 46,XY gonadal dysgenesis
- HPC:197 : 46,XY gonadal dysgenesis
- HPC:384 : Gonadoblastoma in 46,XY gonadal dysgenesis

Definition: 46,XY gonadal dysgenesis with female phenotype (Swyer syndrome) appear to be normal phenotypic females. However, they do not develop secondary sexual characteristics at puberty, do not menstruate, and have ’streak gonads.’ They are chromatin negative and have a 46,XY karyotype.

Disorders of sex development (DSDs) are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical.

XY gonadal dysgenesis (MIM.400044) is a DSD in which the embryonic gonadal development is defective.

Clinically, XY gonadal dysgenesis may manifest as complete (complete XY gonadal dysgenesis) or partial forms (partial XY gonadal dysgenesis).

Complete XY gonadal dysgenesis in 46,XY individuals is characterized by a female phenotype with full development of unambiguous female genitalia, normally developed Müllerian structures, and streak gonads. In general, these patients come for clinical assistance because of delayed puberty.

Conversely, 46,XY partial gonadal dysgenesis is characterized by partial testicular differentiation therefore ambiguous genitalia is usually observed in the newborn period. Gonadal histology is variable but frequently consists of hypoplastic testicular tubules intermixed with areas of ovarian stroma. Internal ducts typically consist of a combination of Wolffian and Mullerian ducts.

The failure in testis development may be a consequence of mutations in the SRY gene. The Y-chromosome-located SRY gene encodes a small testis-specific protein containing a DNA-binding motif known as the HMG (high mobility group) box. However, mutations in SRY are not frequent especially in cases of 46,XY partial gonadal dysgenesis. Several sex-determining genes direct the fate of the bipotential gonad to either testis or ovary. It is well known that heterozygous small deletions in 9p, containing DMRT1, can cause complete or partial XY gonadal dysgenesis (MIM.154230) without other symptoms.


- normal female phenotype
- absence of secondary sexual characteristics at puberty
- amenorrhea
- dysgenetic gonad

  • streak gonads
    • unidentifiable fibrovascular streak gonad

- gonadal tumors

  • gonadoblastoma +/- bilateral (8514986)
  • gonadal germ cell tumors
    • gonadoblastoma overgrown by dysgerminoma (7243139)
    • gonadal choriocarcinoma (1695883, 8696173)
    • gonadoblastoma and choriocarcinoma association (8696173)
    • dysgenetic gonad with mixed germ cell tumors associating malignant teratoma, dysgerminoma, yolk sac tumor, choriocarcinoma
    • true histiocytic malignancy associated with a malignant teratoma (1346359)


- SRY inactivating mutations (15%)

  • 46, XY gonadal dysgenesis can be associated with point mutations or deletions of the SRY gene (MIM.480000), but also in some cases with changes in the X chromosome.

- deletion of terminal 9p (including DMRT) (17644778)
- Denys-Drash syndrome (WT1 germline mutations)
- DAX1 duplication-associated DSD

  • Xp21.2 interstitial duplication containing the DAX1 gene
  • DAX1 duplications at Xp11.2 (17504899)

See also

- intersex

  • XY intersex

- mixed gonadal dysgenesis
- XY partial gonadal dysgenesis


- Koo CH, Reifel J, Kogut N, Cove JK, Rappaport H. True histiocytic malignancy associated with a malignant teratoma in a patient with 46XY gonadal dysgenesis. Am J Surg Pathol. 1992 Feb;16(2):175-83. PMID: 1346359

- Dumic M, Jukic S, Batinica S, Ille J, Filipovic-Grcic B. Bilateral gonadoblastoma in a 9-month-old infant with 46,XY gonadal dysgenesis. J Endocrinol Invest. 1993 Apr;16(4):291-3. PMID: 8514986

- Ultrastructure of gonadoblastoma and disgerminoma (seminoma) in a patient with XY gonadal dysgenesis. Bjersing L, Cajander S. Cancer. 1977 Sep;40(3):1127-37. PMID: 561649