• Clinical science

Disorders of sex development


Disorders of sex development are a group of congenital conditions that affect the development of the chromosomal, gonadal, or phenotypic sex. The underlying genetic mutations affect the number and function of sex chromosomes (e.g., in Turner syndrome), lead to structural changes with altered sensitivity of hormone receptors (e.g., androgen insensitivity syndrome), or alter the function of enzymes responsible for sex hormone synthesis (e.g., congenital adrenal hyperplasia). The most characteristic clinical feature is the development of a sexual phenotype which does not correspond to the sexual genotype. Other common features include reduced fertility or infertility and concomitant organ malformations (e.g., cardiac abnormalities). Disorders of sex development can also present with difficulties in gender identification and cause considerable psychological distress. The diagnosis of these conditions is based on characteristic clinical features, evaluation of hormone levels, and genetic testing. Management includes hormone substitution, possibly sex reassignment surgery, and psychological counseling.

Congenital adrenal hyperplasia

Androgen insensitivity syndrome

  • Incidence:approx. 1:20,000 genetically male individuals in the US [1]
  • Etiology: X-linked recessive mutation of the gene encoding the androgen receptor
  • Karyotype: 46,XY
  • Pathophysiology: Defects in the androgen receptor result in varying degrees of end-organ insensitivity to androgens.
  • Clinical features
  • Diagnosis
  • Treatment: depends on receptor status as well as on the patient's phenotype and gender identity
    • Hormone treatment
    • Gonadectomy for intra-abdominal/intra-labial testicles
      • Typically performed after puberty
      • Prevents malignant transformation of the abnormally localized gonads
    • Psychological support


Aromatase deficiency


5-alpha-reductase deficiency

  • Synonym: pseudovaginal perineoscrotal hypospadias (PPSH)
  • Etiology: rare autosomal recessive loss-of-function mutation of chromosome 2
  • Karyotype: 46,XY
  • Pathophysiology
  • Clinical features
    • Female external genitalia at birth, sometimes with pseudovaginal perineoscrotal hypospadias
    • Internal urogenital organs are male
    • In puberty, increasing synthesis of testosterone leads to virilization (phallic growth, testicular descent, development of male gender identity).
  • Diagnostics
  • Therapy


Klinefelter syndrome


Ovotesticular disorder of sex development

Turner syndrome


Pure gonadal dysgenesis


Swyer syndrome


Kallmann syndrome