Errors in Sex Determination

Introduction: The development of the sex organs and associated structures proceeds through a number of steps over a significant period of time from early in pregnancy through puberty. The metabolic controls usually produce normally functioning males and females, but sometimes errors occur. Androgen Insensitivity Syndrome: The fetus has a Y-chromosome and the developing testes produce testosterone in the normal way. However, the various receptors around the body are insensitive to the testosterone. As a result, continued development of male organs ceases and the child usually appears female at birth. The condition is sometimes called "testicular feminization." It is caused by an X-linked recessive trait (the mutant gene is located on the X-chromosome). Two other well-known recessive conditions associated with genes on the X-chromosome are red-green color blindness and hemophilia. Click for More Info Congenital Adrenal Hyperplasia (CAH): The adrenal glands in the developing fetus fail to properly produce cortisol from 17-hydroxy-progesterone, most often as a result of a mutation in the gene on the short arm of Chromosome 6 for the enzyme 21-hydroxylase. As a result of the shortage of cortisol, the brain releases more ACTH (Adrenocorticotropic hormone, corticotropin), which in turn induces overgrowth (hyperplasia) and overactivity of the steroid-producing cells of the adrenal cortex. All forms of congenital adrenal hyperplasia are autosomal recessive disorders, so both sexes are affected with equal frequency. The higher level of androgens (male hormones) that result from the elevated activity of the adrenal cortex can cause early puberty in males and the growth of some male characteristics in females: a penis, body hair, masculinization of the brain, etc. 5-alpha-reductase deficiency (5-ARD): The development of male external genitalia is promoted by dihydroxytestosterone. The enzyme that converts testostrone to dihydroxytestosterone is 5-alpha-reductase. A mutation in the gene on the short arm of Chromosome 2 inactivates the enzyme and prevents the production of dihydroxytestosterone. Some affected babies appear female at birth and are raised as female, only to have the rise in testosterone at puberty complete male development. Chromosomal Conditions: During meiosis, occasionally the chromosomes do not separate properly (nondisjunction). One gamete may contain an additional X chromosome or may contain neither an X nor Y chromosome. Human individuals with unusual chromosomal constitutions such as 45X (Turner Syndrome) or 47XXX karyotypes (Triplo-X) are female and individuals with 47XXY karyotype (Klinefelter Syndrome) are male.

Adapted and excerpted from: Genetic Errors of Metabolism. Congenital adrenal hyperplasia Congenital Adrenal Hyperplasia 5-alpha-reductase deficiency Turner syndrome