Table 4.

Characteristics of 46, XY disorders of sex development

	Inheritance and Gene	Genitalia	Wolffian duct derivatives	Mullerian duct derivatives	Gonads	Typical features	Hormone profile
Leydig cell hypoplasia	Autosomal Recessive, LH/HCGR	Female, hypospadias or micropenis	Hypoplastic	Absent	Testes	Underandrogenization with variable failure of sex hormone production at puberty	Low T and DHT, elevated LH and FSH, exaggerated LH response to LHRH, poor T and DHT response to hCG stimulation
Lipoid CAH	Autosomal Recessive, StAR	Female, rarely ambiguous or male	Hypoplastic or normal	Absent	Testes	Severe adrenal insufficiency in infancy with salt loss, failure of pubertal development, rare cases associated with isolated glucocorticoid deficiency	Usually deficient of glucocorticoids, mineralocorticoids and sex steroids
P450SCC def	Autosomal Recessive, CYP11A1	Female, rarely ambiguous or hypospadias	Hypoplastic or normal	Absent	Testes	Severe adrenal insufficiency in infancy with salt loss ranging to milder adrenal insufficiency with onset in childhood	Usually deficient of glucocorticoids, mineralocorticoids and sex steroids
3β‐hydroxysteroid dehydrogenase II def	Autosomal Recessive, HSD3B2	Ambiguous, hypospadias	Normal	Absent	Testes	Severe adrenal insufficiency in infancy ± salt loss, poor androgenization at puberty with gynaecomastia	Increased concentrations of Δ5 C21‐ and C19‐ steroids, 17 hydroxypregnenolone and DHEA suppressible by dexamethasone
Combined 17α‐hydroxylase/17,20‐lyase def	Autosomal Recessive, CYP17A1	Female, ambiguous, hypospadias or micropenis	Absent or hypoplastic	Absent	Testes	Absent or poor virilization at puberty, gynaecomastia, hypertension	Decreased T, increased LH and FSH, increased plasma deoxycorticosterone, corticosterone and progesterone, decreased plasma renin activity, low renin hypertension with hypokalaemic alkalosis
Isolated 17,20‐lyase def	Autosomal Recessive, CYP17A1, usually affecting key redox domains, alternatively caused by cytochrome b5 mutations (CYB5)	Female, ambiguous or hypospadias	Absent or hypoplastic	Absent	Testes	Absent or poor androgenization at puberty, gynaecomastia	Decreased T, DHEA, androstenedione and oestradiol, abnormal increase in plasma 17‐hydroxyprogesterone and 17‐hydroxypregnenolone, increased LH and FSH, increased ratio of C21‐deoxysteroids to C19‐steroids after hCG stim
P450 oxidoreductase def	Autosomal Recessive, POR	Ambiguous, hypospadias or normal male	Absent or hypoplastic	Absent	Testes	Variable androgenization at birth and puberty, glucocorticoid deficiency, features of skeletal malformations. Maternal androgenization during pregnancy onset second trimester possible	Combined P450c17 and P450c21 insuff, normal or low cortisol with poor response to ACTH stim, elevated 17‐hydroxyprogesterone, T low
17β‐hydroxysteroid dehydrogenase type 3 def	Autosomal Recessive HSD17B3	Female, ambiguous, blind vaginal pouch	Present	Absent	Testes	Androgenization at puberty, gynaecomastia variable	Increased plasma estrone, decreased ratio of testosterone/androstenedione and oestradiol after hCG stim, increased FSH and LH
5α‐reductase‐2 def	Autosomal Recessive SRD5A2	Ambiguous, micropenis, hypospadias, blind vaginal pouch	Normal	Absent	Testes	Decreased facial and body hair, no temporal hair recession, prostate not palpable	Decreased ratio of 5α/5β C21‐ and C19‐ steroids in urine, increased T/DHT ratio beforeand after hCG stim, modest increase in LH, decreased conversion of T to DHT in vitro
CAIS	X‐linked Recessive AR	Female with blind vaginal pouch	Often present depending on mutation type	Absent or vestigial	Testes	Scant or absent pubic and axillary hair, breast development and female body habitus at puberty, primary amenorrhoea	Increased LH and T, increased oestradiol, FSH levels normal or slightly increased, resistance to androgenic and metabolic effects of T (may be normal in some cases)
PAIS	X‐linked Recessive AR	Ambiguous with blind vaginal pouch, isolated hypospadias, normal male with infertility (mild)	Often normal	Absent	Testes	Decreased to normal axillary and pubic hair, facial and body hair, gynaecomastia common at puberty	Increased LH and T, increased oestradiol, FSH levels may be normal or slightly increased, partial resistance to androgenic and metabolic effects of T

DHT, dihydrotestosterone; FSH, follicle‐stimulating hormone; hCG, human chorionic gonadotropin; LH, luteinising hormone; T, testosterone; DHEA, dehydroepiandrosterone; ACTH, adrenocorticotropin hormone.