[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [Urogenital system](https://durgical.com/en/embryology/#a-urogenital) › Differences of sex development: CAH, AIS and 5α-reductase

[Embryology](https://durgical.com/en/embryology/) · [Urogenital system](https://durgical.com/en/embryology/#a-urogenital)

# Differences of sex development: CAH, AIS and 5α-reductase

- Malformation

Conditions in which chromosomes, gonads and genitalia do not follow the typical pattern. They have specific causes that can be investigated.

Updated 2026-11-01

**See it in 3D:** [Clitoris](https://durgical.com/en/anatomy/clitoris/) · [Labia majora](https://durgical.com/en/anatomy/labium-majus-of-vulva/) · [Scrotum](https://durgical.com/en/anatomy/scrotum/) · [Body of uterus](https://durgical.com/en/anatomy/body-of-uterus/) · [Vagina](https://durgical.com/en/anatomy/vagina/) · [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/) · [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/)

## Key points

- Language: “differences of sex development”; old terms such as “hermaphrodite” or “pseudohermaphrodite” are no longer used.
- 21-hydroxylase deficiency (CYP21A2, autosomal recessive): the commonest cause of atypical genitalia in a 46,XX newborn; uterus and ovaries are normal.
- The salt-wasting form causes hyponatraemia and hyperkalaemia in the first weeks: an emergency.
- Complete androgen insensitivity (AR gene, X-linked): 46,XY, testes, no uterus, short blind vagina, breast development at puberty, little body hair.
- 5α-reductase type 2 deficiency (SRD5A2, autosomal recessive): 46,XY, Wolffian ducts present, atypical external genitalia at birth and virilization at puberty.
- Turner (45,X) and Klinefelter (47,XXY) syndromes sit among the sex chromosome DSD.

## What it is

Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal or anatomical sex does not match the typical pattern. They are classified by karyotype as 46,XX DSD, 46,XY DSD and sex chromosome DSD. Three causes cover most exam questions: congenital adrenal hyperplasia from 21-hydroxylase deficiency, androgen insensitivity and 5α-reductase type 2 deficiency.

## Key facts

- First test for atypical genitalia: the karyotype.
- Presence or absence of a uterus tells whether AMH (and so a working testis) was present.
- In CAH, 17-hydroxyprogesterone is high; many programmes include it in newborn screening.
- In 5α-reductase deficiency the testosterone/DHT ratio is raised.
- In androgen insensitivity, testosterone and LH are normal or high.

## Embryological cause

- 21-hydroxylase CAH: the fetal adrenal makes too little cortisol, ACTH rises and precursors are shunted to androgens that virilize the external genitalia of a 46,XX fetus (clitoromegaly, labioscrotal fusion). There is no AMH, so uterus and tubes are normal.
- Androgen insensitivity: the androgen receptor does not work. The testis makes AMH (no uterus) and testosterone, but the Wolffian ducts are not kept and the external genitalia develop as female. The lower vagina, from the urogenital sinus, does form.
- 5α-reductase type 2 deficiency: testosterone acts (normal Wolffian ducts), but there is not enough DHT to masculinize the external genitalia and prostate. At puberty rising testosterone causes partial virilization.
- Sex chromosome DSD: 45,X (Turner, streak gonads), 47,XXY (Klinefelter) and mosaicism such as 45,X/46,XY.

## Three classic causes of DSD compared

| Condition | Karyotype | Gonads | Uterus | External genitalia |
| --- | --- | --- | --- | --- |
| 21-hydroxylase CAH | 46,XX | Ovaries | Yes | Virilized |
| Complete androgen insensitivity | 46,XY | Testes | No | Female |
| 5α-reductase deficiency | 46,XY | Testes | No | Atypical; virilize at puberty |

## Markers

- CYP21A2
- AR
- SRD5A2
- SRY
- 17-OHP

## How it presents

- 46,XX newborn with CAH: clitoromegaly and fused labia, no palpable gonads; vomiting, dehydration and shock in the salt-wasting form.
- Complete insensitivity: a girl with an inguinal hernia containing a testis, or a teenager with primary amenorrhoea, developed breasts and sparse pubic hair.
- Partial insensitivity: a spectrum of atypical genitalia, from hypospadias to clitoromegaly.
- 5α-reductase deficiency: atypical or female genitalia at birth; at puberty the phallus and muscle mass grow, with little facial hair and a small prostate.
- Signs pointing to a DSD: proximal hypospadias with cryptorchidism, bilateral impalpable testes, an inguinal mass in a girl, clitoromegaly.

## Diagnosis

- Karyotype (and SRY testing): separates 46,XX, 46,XY and sex chromosome DSD.
- 17-hydroxyprogesterone and serum electrolytes when CAH is suspected.
- Pelvic ultrasound or MRI: presence of a uterus and location of the gonads.
- Testosterone, DHT, LH, FSH and anti-Müllerian hormone to separate disorders of androgen synthesis from disorders of action.

## Memory aid

“Uterus present = no testis was there; uterus absent = AMH was there.” Then ask whether the androgen was too much (CAH), not heard (receptor) or not converted (5α).

## Test yourself

Think of the answer, then tap the question to see it.

## What is the commonest cause of atypical genitalia in a 46,XX newborn?

Congenital adrenal hyperplasia from 21-hydroxylase deficiency (CYP21A2 gene), which produces excess adrenal androgens.

## Why does a person with complete androgen insensitivity have a short vagina but no uterus?

AMH from the testes removes the Müllerian ducts (uterus and upper vagina), while the lower vagina forms from the urogenital sinus without needing androgens.

## What separates 5α-reductase deficiency from complete androgen insensitivity?

In 5α-reductase deficiency testosterone acts: Wolffian ducts are present and virilization occurs at puberty; in complete insensitivity androgens act in no tissue.

## Which electrolyte pattern suggests salt-wasting CAH?

Hyponatraemia with hyperkalaemia in the first weeks of life, from lack of aldosterone.

## What is the first test for a newborn with atypical genitalia?

The karyotype, together with electrolytes and 17-hydroxyprogesterone because of the risk of salt-wasting CAH.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/embryology/differences-of-sex-development-cah-ais-and-5-reductase/)

## See it in 3D

The structures of Durgical's 3D anatomy where it is found.

- [Clitoris](https://durgical.com/en/anatomy/clitoris/)
- [Labia majora](https://durgical.com/en/anatomy/labium-majus-of-vulva/)
- [Scrotum](https://durgical.com/en/anatomy/scrotum/)
- [Body of uterus](https://durgical.com/en/anatomy/body-of-uterus/)
- [Vagina](https://durgical.com/en/anatomy/vagina/)
- [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/)
- [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/)

## Related

- [Sex determination: SRY, anti-Müllerian hormone and testosterone](https://durgical.com/en/embryology/sex-determination-sry-anti-mullerian-hormone-and-testosterone/)
- [External genitalia and their male–female homologues](https://durgical.com/en/embryology/external-genitalia-and-their-male-female-homologues/)
- [Genital ducts: Wolffian (mesonephric) and Müllerian (paramesonephric)](https://durgical.com/en/embryology/genital-ducts-wolffian-and-mullerian/)
- [Gonads and the descent of the testis](https://durgical.com/en/embryology/gonads-and-the-descent-of-the-testis/)
- [Adrenal gland: cortex from mesoderm, medulla from neural crest](https://durgical.com/en/embryology/adrenal-gland-cortex-from-mesoderm-medulla-from-neural-crest/)
- [Hypospadias and epispadias](https://durgical.com/en/embryology/hypospadias-and-epispadias/)
- [Cryptorchidism](https://durgical.com/en/embryology/cryptorchidism/)
- [Uterine anomalies: bicornuate, septate, didelphys, Müllerian agenesis](https://durgical.com/en/embryology/uterine-anomalies-bicornuate-septate-didelphys-mullerian-agenesis/)
- [Androgens, diethylstilbestrol and other hormones](https://durgical.com/en/embryology/androgens-diethylstilbestrol-and-other-hormones/)
- [Meiosis and nondisjunction: where trisomies come from](https://durgical.com/en/embryology/meiosis-and-nondisjunction-where-trisomies-come-from/)

## Related conditions

- [Congenital adrenal hyperplasia due to 21-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/)
- [Turner syndrome](https://durgical.com/en/conditions/turner-syndrome/)
- [Klinefelter syndrome (47,XXY)](https://durgical.com/en/conditions/klinefelter-syndrome/)
- [Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-11-hydroxylase-deficiency/)
- [Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-17-hydroxylase-deficiency/)
- [Adrenal crisis](https://durgical.com/en/conditions/adrenal-crisis/)

[← All of embryology](https://durgical.com/en/embryology/)

Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.

Sources: [Ambiguous Genitalia and Disorders of Sexual Differentiation - StatPearls - NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK557435/) (StatPearls Publishing (NCBI Bookshelf), 2023); [21-hydroxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency/) (MedlinePlus, U.S. National Library of Medicine, 2024); [Androgen insensitivity syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/androgen-insensitivity-syndrome/) (MedlinePlus, U.S. National Library of Medicine, 2024); [5-alpha reductase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/5-alpha-reductase-deficiency/) (MedlinePlus, U.S. National Library of Medicine, 2024).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/differences-of-sex-development-cah-ais-and-5-reductase/