•
5α-reductase deficiency (5-ARD) – an
autosomal recessive condition caused by a mutation of the
5-alpha reductase type 2 gene. It only affects people with Y chromosomes, namely genetic males. People with this condition are fertile, with the ability to father children, but may be raised as females due to ambiguous or feminized genitalia. •
17β-Hydroxysteroid dehydrogenase deficiency – a condition characterized by impaired androgen and estrogen synthesis in males and females, respectively. Results in pseudohermaphroditism/undervirilization in males. •
46,XX/46,XY – a
chimeric condition where the person shows variable karyotype in the 23rd chromosome pair, resulting from embryonic merging. It can vary in presentation from phenotypically normal, to ambiguous. •
Androgen insensitivity syndrome (AIS) – a condition which affects a genetic male's virilization. A person with androgen insensitivity syndrome produces androgens and testosterone but their body does not recognize it, either partially or completely.
Mild androgen insensitivity syndrome generally causes no developmental issues and people with this form are raised as males.
Partial androgen insensitivity syndrome results in ambiguous genitalia and there is no consensus regarding whether to raise a child with this form as male or female.
Complete androgen insensitivity syndrome causes a genetic male to have a vagina (often incompletely developed, nearly always blind-ending), breasts, and a clitoris; people with this form are raised as females. •
Aphallia – a rare condition where a XY male is born without a
penis. As of 2017, only 100 cases have been reported in literature. •
Aromatase deficiency – a disorder which, in females, is characterized by androgen excess and estrogen deficiency, and can result in inappropriate virilization, though without pseudohermaphroditism (i.e., genitals are phenotypically appropriate) (with the exception of the possible incidence of
clitoromegaly). Aromatase deficiency can also be caused by mutations in P450 oxidoreductase gene. •
Aromatase excess syndrome (familial hyperestrogenism) - a condition that causes excessive
estrogen production, resulting in feminization without pseudohermaphroditism (i.e., male genitalia at birth and female secondary sexual characteristics at puberty) in males and hyperfeminization in females. •
Campomelic dysplasia – a condition caused by
de novo autosomal dominant mutations in the
SOX9 gene, causing bowing of the limbs, sex reversal in around two thirds of 46,XY males (but not in 46,XX females), and
respiratory insufficiency. While in roughly 95% of cases, death occurs in the
neonatal period due to respiratory distress, those that live past infancy typically survive to become adults. •
Clitoromegaly – a
clitoris that is considered larger than average. While clitoromegaly may be a symptom of an
intersex condition, it may also be considered a normal variation in clitoris size. Clitoromegaly causes no health issues. Surgical reduction of the clitoris or its complete removal may be performed to normalize the appearance of the genitalia. While
female genital mutilation is outlawed in many countries, reduction or the removal of the clitoris in cases of clitoromegaly are generally exempt, despite the fact that it is a nontherapeutic and sexually damaging surgery. Clitoromegaly may also be caused by females using
testosterone or
anabolic steroids for purposes related to
female to male gender transition or
bodybuilding. •
Combined 17α-hydroxylase/17,20-lyase deficiency – a condition which presents as a combination of the symptoms of
congenital adrenal hyperplasia and
isolated 17,20-lyase deficiency. See those two conditions for more information. •
Complete androgen insensitivity syndrome (CAIS) – a condition which completely affects a genetic male's ability to recognize
androgens. It is considered a form of
androgen insensitivity syndrome and is the most severe form. People with complete androgen insensitivity are raised as females and usually do not discover they are genetic males until they experience
amenorrhoea in their late teens or they need medical intervention due to a
hernia caused by their
undescended testes. Complete androgen insensitivity syndrome results in a genetic male having a vagina, clitoris, and breasts which are capable of
breastfeeding. However, they will not have
ovaries or a
uterus. Because they do not have ovaries or sufficiently developed testicles, people with complete androgen insensitivity syndrome are
infertile. •
Congenital adrenal hyperplasia (CAH) – a condition that causes excessive
androgen production, which causes excessive virilization. It is most problematic in genetic females, where severe virilization can result in fusion of the labia and an enlarged clitoris. Females with this condition are usually fertile, with the ability to become pregnant and give birth. The salt-wasting variety of this condition is fatal in infants if left untreated. •
Denys–Drash syndrome and the related
Frasier syndrome – similar rare conditions arising from
de novo autosomal dominant mutations in the
WT1 gene, causing symptoms ranging from undervirilization to complete sex reversal with persistent
Müllerian ducts in affected 46,XY males (but not in 46,XX females). The disorders are invariably fatal before the age of 15, causing kidney failure due to
nephrotic syndrome. •
Estrogen insensitivity syndrome (EIS) – the estrogen counterpart to androgen insensitivity syndrome. Extremely rare, with only one verified case having been reported; a biological male presented with tall stature, a heightened risk of osteoporosis, and sterility. •
Gartner's duct cyst – persistent Wolffian Ducts in XX females. •
Gonadal dysgenesis – any congenital developmental disorder of the reproductive system characterized by a progressive loss of
primordial germ cells on the developing gonads of an embryo. •
Herlyn-Werner-Wunderlich syndrome – a disorder where the Müllerian ducts fail to fuse during embryonic development, leading to the presence of 2 vaginas, 2 uteruses, and a single kidney. Can also affect the spleen, bladder and other urogenital structures. •
Isolated 17,20-lyase deficiency – a condition that is characterized by either partial or complete inability to produce androgens and estrogens. Results in partial or complete feminization and undervirilization in males and in a delayed, reduced, or absent puberty in both sexes, in turn causing sexual infantilism and infertility, among other symptoms. •
Klinefelter syndrome (47,XXY and XXY syndrome) – a condition that describes a male born with at least one extra X chromosome. Though the most common variation is 47,XXY, a man may also be
48,XXXY or
49,XXXXY. It is a common occurrence, affecting 1 in 500 to 1,000 men. About 1 in 50,000 men are affected by variant 48,XXXY (Two extra X) and 1 in 100,000 men affected by variant 49,XXXXY (Three extra X). While some men may have no issues related to the syndrome, some may experience
gynecomastia,
micropenis, cognitive difficulties,
hypogonadism, reduced fertility/
infertility, and/or little or no
facial hair.
Testosterone therapy may be pursued by men who desire a more masculine appearance and those with gynecomastia may opt to undergo a
reduction mammoplasty. Men who wish to father children may be able to do so with the help of
IVF. •
Lipoid congenital adrenal hyperplasia – an endocrine disorder that arises from defects in the earliest stages of
steroid hormone synthesis: the transport of
cholesterol into the
mitochondria and the conversion of cholesterol to
pregnenolone—the first step in the synthesis of all steroid hormones. •
Mild androgen insensitivity syndrome (MAIS) – a condition which mildly affects a genetic male's ability to recognize
androgens. It is considered a form of
androgen insensitivity syndrome and is considered the least severe form. While men generally do not need any specialized medical care related to this form, mild androgen insensitivity syndrome may result in
gynecomastia and
hypospadias. Neither gynecomastia nor hypospadias require surgical intervention or adversely affect a man's health though some men may opt to undergo surgery to remove their breasts and/or repair their hypospadias. Men with mild androgen insensitivity syndrome may have reduced fertility. •
Mixed gonadal dysgenesis – a condition of unusual and asymmetrical gonadal development leading to an unassigned
sex differentiation. A number of differences have been reported in the
karyotype, most commonly a
mosaicism 45,X/ 46,XY. •
Ovotesticular disorder (also called true hermaphroditism) – a rare condition where an individual has both ovarian and testicular tissue. It is the rarest DSD with at least 500 cases being reported in literature. •
Partial androgen insensitivity syndrome (PAIS) – a condition which partially affects a genetic male's ability to recognize
androgens. It is considered a form of
androgen insensitivity syndrome and while it is not as severe as
complete androgen insensitivity syndrome, it is more severe than
mild androgen insensitivity syndrome. Partial androgen insensitivity syndrome causes major problems with
gender assignment because it causes ambiguous genitalia such as a
micropenis or
clitoromegaly in addition to breast development. People with partial androgen insensitivity syndrome who are assigned as males may undergo testosterone therapy to virilize their body while those who are assigned as females may undergo a surgical reduction of the clitoris and/ or estrogen therapy. •
Penoscrotal transposition (PST) – a group of congenital defects involving an abnormal spatial arrangement of penis and scrotum. •
Persistent Müllerian duct syndrome – a condition where fallopian tubes, uterus, or the upper part of the vagina are present in an otherwise normal male. •
Pseudovaginal perineoscrotal hypospadias (PPSH) – a form of ambiguous genitalia which results in a phallic structure that is smaller than a penis but larger than a clitoris, a
chordee,
hypospadias, and a shallow vagina. •
Swyer syndrome (Pure Gonadal Dysgenesis or XY gonadal dysgenesis) – a type of
hypogonadism in a person whose
karyotype is 46,XY. The person is externally female with
streak gonads, and left untreated, will not experience
puberty. Such gonads are typically surgically removed (as they have a significant risk of developing tumors) and a typical medical treatment would include
hormone replacement therapy with female hormones. •
Turner syndrome (Ullrich-Turner syndrome and gonadal dysgenesis) – a condition that describes a female born with only one X chromosome or with an abnormal X chromosome, making her karotype 45,X0. It occurs in 1 in 2,000 to 5,000 females. Turner syndrome can cause numerous health and development problems, including but not limited to short stature,
lymphedema,
infertility,
webbed neck,
coarctation of the aorta,
ADHD,
amenorrhoea, and
obesity. •
Müllerian agenesis (
Mayer-Rokitansky-Küster-Hauser syndrome or vaginal agenesis) – a condition that causes the uterus and other reproductive organs in a 46,XX female to be small or absent, as well as the vaginal canal itself. It affects 1 out of 4,500 to 5,000 females and can also come with skeletal or endocrine system issues at conception. •
XX testicular DSD – a condition where an individual with an XX karyotype has a male appearance. Genitalia can range from normal to ambiguous genitalia. It is estimated to occur in 1 in 20,000 males. == Diagnosis and symptoms ==