Disorders of Sex Development - Conditions

Conditions

• 48, XXXX (also known as tetrasomy X, quadruple X, and XXXX syndrome) - A condition that describes a female with two extra female chromosomes. It is considered a variation of Triple X syndrome. Women with 48, XXXX may or may not have issues associated with the condition though most are developmentally delayed and only about 50% undergo puberty normally.
• 48, XXYY (also known as XXYY syndrome) - A condition that describes a male with one extra female chromosome and one extra male chromosome. It occurs in 1 in 18,000 to 40,000 male births. 48, XXYY may result in infertility, low testosterone, and neurodevelopmental disorders like ADHD or autism but some men have no issues.
• 49, XXXXX (also known as pentasomy X and XXXXX syndrome) - A condition that describes a female with three extra female chromosomes. It is considered a variant of Triple X syndrome. Women with 49, XXXXX usually suffer from numerous health issues such as patent ductus arteriosus, scoliosis, kidney hypoplasia, and abnormal lobulation of the lungs. Physical deformities include microcephaly, micrognathia, and webbing of the neck.
• 49, XXXXY - A condition that describes a male with three extra female chromosomes. It is rare, occurring in 1 in 85,000 to 100,000 males. It is considered a variation of Klinefelter's syndrome. Men with 49, XXXXY syndrome often suffer from mental retardation.
• 5α-reductase deficiency (also known as 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 amibiguous 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 and in excessive virilization of adult females.
• Androgen insensitivity syndrome (also known as AIS) - A condition which affects a genetic male's virilization. A man 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, breasts, and a clitoris and people with this form are raised as females.
• Aphallia - A rare occurrence where a male is born without a penis or where a female is born without a clitoris. As of 2005, only 75 cases of aphallia have been documented. It should not be confused with intentional or accidental amputation of the genitalia.
• Aposthia - A congenital defect where a male is born without a foreskin.
• Aromatase deficiency - A disorder in 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 excess syndrome (also known as 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.
• 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 in 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 (also known as CAIS) - A condition which completely affects a man'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 (also known as 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 her having vaginal agenesis (absence of vagina) and a functional penis which is capable of penetrative intercourse. 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.
• Diphallia (also known as penile duplication, diphallic terata, and diphallasparatus) - A condition where a male is born with two penises. It's extremely rare, with only 100 cases being recorded since 1609 and an occurrence rate of 1 in 5,500,000 in the United States. The penises may be side by side or one on top of the other, being of equal size or with one penis being distinctively larger than the other, and both penises may be suitable for urination and intercourse. Men with diphallia may be sterile.
• 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.
• Isolated 17,20-lyase deficiency - A condition that is characterized by an 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's syndrome (also known as 47, XXY and XXY syndrome) - A condition that describes a male born with at least one extra female 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. 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.
• Leydig cell hypoplasia - A condition solely affecting biological males which is characterized by a partial or complete inactivation of the luteinizing hormone receptor, resulting in stymied androgen production. Patients may present at birth with a fully female phenotype, ambiguous genitalia, or only mild genital defects such as micropenis and hypospadias. Upon puberty, sexual development is either impaired or fully absent.
• Micropenis (also known as microphallus) - A penis that measures 3 inches (7.62 centimeters) or less in length when erect. It is a common condition, occurring in 1 in 200 men. Micropenis may be the result of undervirilization during fetal development or may be caused by an underlying intersex condition, such as mild androgen insensitivity syndrome, partial androgen insensitivity syndrome, or Kleinfelter's syndrome. It may also be considered a natural variation of penis size. While the majority of men have no issues with having a micropenis, some may opt to use a prosthetic penis or undergo penile enlargement to increase the size of their penis.
• Mild androgen insensitivity syndrome (also known as MAIS) - A condition which mildly affects a man'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 surgerical 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.
• Partial androgen insensitivity syndrome (also known as PAIS) - A condition which partially affects a man'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 surgical reduction of the clitoris and/ or estrogen therapy.
• Pseudovaginal perineoscrotal hypospadias (also known as 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.
• Triple X syndrome - A condition that describes a female born with an extra female chromosome, making her karotype 47, XXX. It is a common occurrence, affecting 1 in 1,000 females. It generally causes no health issues or abnormal development.
• Turner syndrome (also known as Ullrich-Turner syndrome and gonadal dysgenesis) - A condition that describes a female born without a female chromosome or with an abnormal female chromosome, making her karotype 45, XO. It occurs in 1 in 2,000 to 5,000 females. Turner syndrome causes numerous health and development problems, including but not limited to short stature, lymphedema, infertility, webbed neck, coarctation of the aorta, ADHD, amenorrhoea, and obesity.
• Uterus didelphys (also known as double uterus) - A condition where a female is born with two uteri. It is often accompanied by two vaginas. It is generally not considered a health issue and women with uterus didelphys usually have normal sex lives and pregnancies.