Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals

Hormones (Athens). 2010 Jul-Sep;9(3):218-131. doi: 10.14310/horm.2002.1272.


There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. Changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DSD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. Basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.

Publication types

  • Review

MeSH terms

  • Chromosomes, Human, X*
  • Female
  • Gene Expression Regulation, Developmental
  • Genitalia / abnormalities*
  • Genotype
  • Gonadal Dysgenesis, 46,XX / classification*
  • Gonadal Dysgenesis, 46,XX / genetics
  • Gonadal Dysgenesis, 46,XX / physiopathology
  • Humans
  • Karyotyping
  • Male
  • Phenotype
  • Sex Determination Analysis
  • Sex Determination Processes*
  • Sexual Development / genetics*
  • Terminology as Topic*