Chapter 108. Sexual Anomalies of Genetic and Hormonal Origin - Review of Medical Embryology Book

Sexual anomalies of genetic origin: sex chromosome alterations may be transmitted by either parent (gonadal dysgeneis) or may occur in the embryo itself, even though the egg initially had a normal chromosome count (true hermaphroditism)

GONDAL DYSGENESIS is due to a failure of disjunction of the sex chromosomes, during gametogenesis, in one of the parents. It may result in

Testicular dysgenesis of Klinefelter, with male morphology and karyotype XXY
Ovarian dysgenesis of Turner, with female morphology and a karyotype of only 1 sex chromosome which is an X and is thus called XO
Mixed gonadal dysgenesis: rare; chromatin-negative nuclei; a testis on one side and an undifferentiated gonad on the other

Internal genitalia are female, but male derivatives of the mesonephric ducts are present
External genitalia range from normal female to intermediate to normal male, but at puberty, neither breast development nor menstruation occurs. One sees varying degrees of virilization

Testicular feminization: rare; appears as a normal female despite the presence of testes and XY sex chromosomes

There is normal breast development at puberty, but no pubic hairs and the vagina ends blindly. Other internal genitalia are also absent or rudimentary
The testes are intra-abdominal or inguinal, but may be in the labia majora
This is an extreme form of male pseudohermaphroditism, but is not intersex because female external genitalia are normal. The testes develop and secrete androgens, but masculinization of the genitals fails because the indifferent external genitalia are insensitive to the androgens

TRUE HERMAPHRODITISM: rare; chromatin-positive nuclei; is secondary to failure of disjunction of sex chromosomes during the first cleavage mitosis of the egg and results in sex mosaics such as XY/XX or XY/XO

The relative quantitative importance of the male component (Y) helps explain the ultimate variations in androgenic effects, including varying degrees of the differentiation of the external genitalia and some subtle variations in somatic morphology

Sexual anomalies of hormonal origin are seen in people with normal genetic makeup. The phenomenon of primary and secondary sexual characteristics leading to pseudohermaphroditism is related to the somatic effects of abnormal androgen secretion

MALE PSEUDOHERMAPHRODITISM: a result of insufficient androgen secretion of an otherwise normal testis with chromatin-negative nuclei and a male 46,XY karyotype

A slight deficiency affects only the last stages of differentiation of the external genitalia, resulting in a small penis, hypospadias, and a valviform appearance of the scrotum. The general morphology is masculine
A severe deficiency shows persistence of the paramesonephic system, and thus, a vagina and uterus coexist with 2 normal vas deferens ducts. The testes are ectopic, and the external genitalia, as well as general morphology, are female type

FEMALE PSEUDOHERMAPHRODITISM is the result of an abnormal virilization of a female fetus that has normal ovaries and a 46,XX karyotype

Virilization may be of endogenous origin, or due to excessive androgen secretion by the fetal adrenal, or of exogenous origin, related to administration of synthetic progesterones or anabolic hormonal medications containing androgens
The paramesonephric system develops normally, but the androgens cause persistence of the mesonephric system and differentiation of the external genitalia toward the male type, resulting in a peniform clitoris and a tendency to closure of the urogenital sinus. Coalescence of the labia majora is completely latent and becomes known by chance through complications of pregnancy or by hysterography
Only severe atresias are found early; they may create difficult treatment problems