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Syndromes of Abnormal Sex Differentiation - Syndromes of Abnormal Sex Differentiation Definition

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5. Micropenis

Androgens are necessary at two different points in fetal development for a normal penis to form: (1) early in fetal life to masculinize the genital tubercle, genital swellings, and genital folds into a penis and scrotum, and (2) later in fetal life to enlarge the penis. Individuals with a micropenis possess a normally developed penis, except that the penis is extremely small. The condition of micropenis is thought to occur in 46,XY individuals if androgen production is insufficient for penile growth after the first part of masculinization of the external genitalia has already occurred. The chart on the following page illustrates the steps of sex differentiation associated with micropenis compared to those of unaffected males and females.

Normal Female DevelopmentMicropenisNormal Male Development
XXXY
ovaries developtestes developtestes develop
no androgen producedandrogens early in fetal life, deficient later in fetal lifeandrogen produced
Wolffian Ducts regressWolffian Ducts developWolffian Ducts develop
no MIS producedMIS producedMIS produced
Mullerian Ducts developMullerian Ducts regressMullerian Ducts regress
external genitalia are femalemicropenisexternal genitalia are male
feminizing pubertypartially masculinizing puberty if exposed to testosterone
OR
feminizing puberty if given estrogen therapy
masculinizing puberty

6. Timing Defect

The many steps of sex differentiation are further complicated by the fact that proper timing of these steps is necessary for normal development. If all of the steps required for male sex differentiation are working, yet these steps are delayed by even a few weeks, the result can be ambiguous differentiation of the external genitalia in a 46,XY individual. The following chart illustrates the steps of sex differentiation associated with a Timing Defect compared to those of normal males

Normal Female DevelopmentTiming DefectNormal Male Development
XXXYXY
ovaries developtestes developtestes develop
no androgen producedandrogen produced at incorrect timeandrogen produced
Wolffian Ducts regressWolffian Ducts developWolffian Ducts develop
no MIS producedMIS producedMIS produced
Mullerian Ducts developMullerian Ducts regressMullerian Ducts regress
external genitalia are femaleexternal genitalia range from female to ambiguousexternal genitalia are male
feminizing pubertypartially masculinizing puberty with testosterone therapy
OR
feminizing puberty with estrogen therapy
masculinizing puberty

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