Syndromes of Abnormal Sex Differentiation - Specific Syndromes of Sex Differentiation

Written by Berdache Jordan

IV. Specific Syndromes of Sex Differentiation

1. Androgen Insensitivity Syndrome (AIS)

Androgen Insensitivity Syndrome occurs when an individual, due to a mutation of the androgen receptor gene, is incapable of responding to androgens. Two forms of AIS exist, Complete AIS (CAIS) and Partial AIS (PAIS).

CAIS

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CAIS affects 46,XY individuals. CAIS patients have normal appearing female external genitalia due to the their complete inability to respond to androgens. This is because the genital tubercle, genital swellings, and genital folds can not masculinize in these patients despite the presence of functional testes located in the abdomen. Similarly, Wolffian duct development does not occur because the Wolffian duct structures can not respond to androgens produced by CAIS patients. Mullerian duct development is inhibited in CAIS individuals because MIS is secreted by the testes.

In addition to possessing normal female external genitalia, CAIS individuals also experience normal female breast development along with sparse pubic and axillary hair growth at puberty. The following chart illustrates the steps of sex differentiation associated with CAIS compared to those of unaffected males and females.

Normal Female Development	CAIS Development	Normal Male Development
XX	XY	XY
ovaries develop	testes develop	testes develop
no androgen produced	androgen produced, but body can not respond	androgen produced
Wolffian Ducts regress	Wolffian Ducts regress	Wolffian Ducts develop
no MIS produced	MIS produced	MIS produced
Mullerian Ducts develop	Mullerian Ducts do not develop	Mullerian Ducts do not develop
external genitalia are female	external genitalia are female	external genitalia are male
feminizing puberty	feminizing puberty without menses	masculinizing puberty

PAIS

PAIS also affects 46,XY individuals. PAIS patients are born with ambiguous external genitalia due to their partial inability to respond to androgens. The genital tubercle is larger than a clitoris but smaller than a penis, a partially fused labia/scrotum may be present, the testes may be undescended, and perineal hypospadius is often present. Wolffian duct development is minimal or nonexistent and the Mullerian duct system does not develop properly.

PAIS patients will experience normal female breast development at puberty, along with a small amount of pubic and axillary hair. The chart on the following page illustrates the steps of sex differentiation associated with PAIS compared to those of unaffected males and females.

Normal Female Development	PAIS Development	Normal Male Development
XX	XY	XY
ovaries develop	testes develop	testes develop
no androgen produced	androgen produced, but body partially unresponsive	androgen produced
Wolffian Ducts regress	Wolffian Ducts develop minimally	Wolffian Ducts develop
no MIS produced	MIS produced	MIS produced
Mullerian Ducts develop	Mullerian Ducts do not develop	Mullerian Ducts do not develop
external genitals are female	external genitalia are ambiguous	external genitalia are male
feminizing puberty	partial masculinizing puberty with testosterone therapy OR feminizing puberty with estrogen therapy	masculinizing puberty