Differences (disorders) of sex development

Last updated: October 30, 2023

Summarytoggle arrow icon

Differences (disorders) of sex development (DSDs; formerly known as “intersex conditions”) are a group of congenital conditions characterized by the atypical development of chromosomal, gonadal, and/or phenotypic sex. The underlying genetic mutations can affect the number and function of sex chromosomes (e.g., in Turner syndrome), cause structural changes that influence the sensitivity of hormone receptors (e.g., androgen insensitivity syndrome), and alter the function of enzymes responsible for sex hormone synthesis (e.g., congenital adrenal hyperplasia). Features vary depending on the specific disorder but may include the mismatch between sexual genotype and phenotype, reduced fertility or infertility, and organ malformations (e.g., cardiac abnormalities). The discrepancy between sexual phenotype and genotype can cause difficulties in gender identification with considerable subsequent psychological distress. The diagnosis of DSDs is based on clinical features, evaluation of hormone levels, and genetic testing. Differential diagnosis should take into account other anomalies of the male and female genital tracts (see the articles on “Anomalies of the female genital tract” and “Infertility”). Treatment should be provided based on patient preference and sexual identification as well as clinical necessity backed by strong ethical principles. If treatment is necessary and/or desired, it generally follows a multidisciplinary approach involving hormone substitution and psychological counseling. Gender affirmation surgery should only be performed if the patient expressly requests the procedure and can provide informed consent.

Overviewtoggle arrow icon

Differences (disorders) of sex development [1]


Classification [2][3]


  • The clinical management of DSDs involves a multidisciplinary approach guided by clinical necessity, patient choice, and strong ethical principles.
  • Physicians should consider the following when determining the best treatment options for patients with DSDs:
  • Types of treatment

Chromosomal abnormalities

Overview of chromosomal abnormalities
Condition Underlying cause Gonadal dysfunction Clinical features
Turner syndrome
Klinefelter syndrome
Double Y syndrome
  • Normal gonadal function

Genetic disorders

Overview of genetic disorders
Condition Underlying cause Gonadal dysfunction Other clinical features
In both 46,XY and 46,XX karyotypes
Congenital adrenal hyperplasia (CAH)
  • Increased or decreased androgen production (depending on the defective/deficient enzyme)
Aromatase deficiency
Ovotesticular disorder of sex development
  • Mixed testicular and ovarian dysgenesis
  • Ovotestis
Kallmann syndrome
  • Mutations in multiple genes responsible for the migration of GnRH-releasing neurons from the olfactory bulbs
SOX9 mutation (campomelic dysplasia)
In 46,XY karyotype only
Androgen insensitivity syndrome
5-alpha reductase deficiency
Persistent Mullerian duct syndrome
17β-hydroxysteroid dehydrogenase 3 deficiency

46,XY gonadal dysgenesis (Swyer syndrome)

  • Mutations of SRY, MAP3K1, NR5A1 or DHH gene
In 46,XX karyotype only
46,XX gonadal dysgenesis
  • Most commonly mutations of BMP15 or NR5A1 gene
46,XX testicular DSD

Congenital malformations of the reproductive system

Overview of congenital malformations of the reproductive system
Condition Underlying cause Clinical features
Anomalies of Mullerian duct fusion
Imperforate hymen

Transverse vaginal septum

Bladder exstrophy

Androgen insensitivity syndrometoggle arrow icon

Aromatase deficiencytoggle arrow icon

5-alpha-reductase deficiencytoggle arrow icon

Klinefelter syndrometoggle arrow icon

Double Y syndrometoggle arrow icon

Contrary to what is frequently still stated in the literature, there is no evidence that individuals with double Y syndrome have higher levels of aggression compared to karyotypically normal male individuals with comparable levels of intelligence.

Ovotesticular disorder of sex developmenttoggle arrow icon

Gonadal dysgenesistoggle arrow icon

Turner syndrometoggle arrow icon

Unlike Klinefelter syndrome, Turner syndrome is not associated with advanced maternal age.

Most patients with Turner syndrome have normal intelligence. [19]

Evaluate for X-linked recessive conditions in patients with Turner syndrome, as this group lacks a second X chromosome.

46,XY gonadal dysgenesistoggle arrow icon

46,XX gonadal dysgenesistoggle arrow icon

46,XX testicular disorder of sex developmenttoggle arrow icon

Kallmann syndrometoggle arrow icon

Persistent Mullerian duct syndrometoggle arrow icon

17β-Hydroxysteroid dehydrogenase 3 deficiency​toggle arrow icon

Referencestoggle arrow icon

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  3. Marino R, Perez Garrido N, Costanzo M, et al. Five New Cases of 46,XX Aromatase Deficiency: Clinical Follow-Up From Birth to Puberty, a Novel Mutation, and a Founder Effect. The Journal of Clinical Endocrinology & Metabolism. 2015; 100 (2): p.E301-E307.doi: 10.1210/jc.2014-2967 . | Open in Read by QxMD
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  25. XYY Syndrome. Updated: January 1, 2012. Accessed: March 6, 2017.
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  40. SOX9 Gene. Updated: April 2, 2019. Accessed: April 11, 2019.
  41. Turner syndrome. Updated: January 1, 2018. Accessed: November 11, 2019.
  42. Intersex. Updated: September 5, 2017. Accessed: December 12, 2019.

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