Syndromes of Abnormal Sex Differentiation - Abnormal Sexual Development

Written by Berdache Jordan

2. Gonadal Dysgenesis

Unlike AIS in which affected individuals possess functioning testes but can not respond to the androgens their testes produce, patients with Gonadal Dysgenesis can respond to androgens but develop abnormal testes which are incapable of producing androgens. Like AIS, two forms of Gonadal Dysgenesis exist (Complete and Partial).

Complete Gonadal Dysgenesis

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Complete Gonadal Dysgenesis affects 46,XY individuals and is characterized by abnormally formed gonads which were originally on the path to testis differentiation (these abnormally formed gonads are referred to as gonadal streaks), female external genitalia, Mullerian duct development, and Wolffian duct regression. Female external genitalia develop due to the failure of the gonadal streaks to produce androgens necessary to masculinize the genital turbercle, genital swellings, and genital folds. Additionally, because the gonadal streaks are incapable of producing either androgens or MIS, the Wolffian duct system regresses while the Mullerian duct system develops. The following chart illustrates the steps of sex differentiation associated with Complete Gonadal Dysgenesis compared to those of unaffected males and females.

Normal Female Development	Complete Gonadal Dysgenesis	Normal Male Development
XX	XY	XY
ovaries develop	streak gonads	testes develop
no androgen produced	no androgen produced	androgen produced
Wolffian Ducts regress	Wolffian Ducts regress	Wolffian Ducts develop
no MIS produced	no MIS produced	MIS produced
Mullerian Ducts develop	Mullerian Ducts develop	Mullerian Ducts regress
external genitalia are female	external genitalia are female	external genitalia are male
feminizing puberty	feminizing puberty with estrogen therapy	masculinizing puberty

Partial Gonadal Dysgenesis

Partial Gonadal Dysgenesis also affects 46,XY individuals, and this condition is characterized by partial testes determination usually accompanied by ambiguous external genitalia at birth. Affected patients may have a combination of Wolffian and Mullerian duct development. The combination of both Wolffian and Mullerian duct development, along with ambiguity of the external structures, indicates that the testes produced more androgens and MIS than those of Complete Gonadal Dysgenesis patients, but not as much as would be seen in normal male development. The chart on the following page illustrates the steps of sex differentiation associated with Partial Gonadal Dysgenesis compared to those of unaffected males and females.

Normal Female Development	Partial Gonadal Dysgenesis	Normal Male Development
XX	XY	XY
ovaries develop	partial testes determination	testes develop
no androgen produced	variable amount of androgen produced	androgen produced
Wolffian Ducts regress	some Wolffian Duct development	Wolffian Ducts develop
no MIS production	variable amount of MIS production	MIS production
Mullerian Ducts develop	some Mullerian Duct development	Mullerian Ducts do not develop
external genitalia are female	ambiguous external genitalia	external genitalia are male
feminizing puberty	feminizing puberty with estrogen therapy OR masculinizing puberty with testosterone therapy	masculinizing puberty