anomalies of sex determination

Definition: disorders of sex determination. Disorders generally associated with an abnormal sex chromosome constitution leading to abnormal gonadal formation.

Additions, deletions, and mosaicism of the sex chromosomes characterize individuals in this category. The appearance of the gonads is variable and ranges from the presence of a streak gonad to a nearly normal female or male gonad on both gross and microscopic examination.

These disorders are subdivided into two broad categories depending on the frequency with which sexual ambiguity occurs.

The pathologist can sometimes suspect that a specimen is from a patient with abnormal sexual development by determining whether a sex chromatin body is present. The Barr body, as it is often called, refers to the mass of densely staining chromatin material found at the periphery of the nucleus in patients with more than one X chromosome.

The nuclei in smooth muscle cells in arteries are particularly useful for this examination. The number of Barr bodies is one less than the number of ‘X’ chromosomes present so that a single Barr body signifies an XX karyotype and three Barr bodies, for example, represent an XXXX karyotype. This simple technique
is often useful in helping to determine whether the patient is a genetic male (XY = zero Barr bodies), genetic female (XX= 1 Barr body), or has some unusual manifestation of multiple X chromosomes.

Types

 sexual ambiguity infrequent

• Klinefelter syndrome
• Turner syndrome
• XX male (XX sex reversal)
• pure gonadal dysgenesis
  • usual form
• WT1-associated DSD (WT1 defects)
  • Denys-Drash syndrome
  • Frasier syndrome

 sexual ambiguity infrequent

• 46,XY disorders of sex development (mixed gonadal dysgenesis)
  • gonadoblastoma
• XY female (XY sex reversal)
• true hermaphrodism

See also

 disorders of sexual development (DSDs)