Support Group

Support Group


Related Conditios


Most of the page is devoted to various XY female intersex conditions other than AIS (AIS having been described in detail elsewhere on the site) and includes a brief mention of the dreaded ‘male-pseudohermaphrodite’ umbrella term!

But firstly we consider some XXX female non-intersex conditions which share common features with some XY female intersex conditions, such as lack of vaginal development. It then looks briefly at true hermaphroditism. The page does not cover XX female intersex conditions such as Congenital Adrenal Hyperplasia (CAH). For information on this type of condition please refer to the web sites of the CAH support groups.

‘XX Female’ Conditions

These will only be considered briefly since the main focus of this site is on ‘XY female’ conditions. However, they do have some features, such as vaginal hypoplasia (underdevelopment), in common with some XY female conditions and we have members of our group who have MRKH. See Overview for a summary of normal female development.

For resources related to XX conditions such as MRKH please refer to our (PDF format) Vaginal Hypoplasia Information Sheet. See also Patricia DeFrain’s Index to Articles, Books etc. on MRKH Syndrome (and Related Issues), a list of publications from Patricia’s (now defunct) website. See also Links to Other Sites.

Note: You need to have a PDF Reader on your PC in order to access PDF files. See About this Site page for more info.

Mayer Rokitansky Kuster Hauser (MRKH) Syndrome

Absent or incomplete vagina, incompletely developed uterus with normal Fallopian tubes and ovaries. Normal breast development and pubic hair. Failure to menstruate.

Mullerian (Duct) Aplasia or Mullerian (Duct) Failure

Absence of the upper vagina, cervix and uterus, with incomplete or absent Fallopian tubes but normal ovarian function. Normal external genitalia, breast development and pubic hair. Lack of menstruation. Exact cause not known (an autosomal X-linked inheritance from the father, an autosomal recessive genetic trait and spontaneous mutation have all been postulated). Sometimes accompanied by abnormalities of the urinary tract (e.g. missing or mis-located kidney) and/or skeletal (mainly spinal) abnormalities.

Confusion exists in the medical community concerning the difference between MRKH and Mullerian Aplasia. Some researchers feel that the presence of a rudimentary uterus and normal Fallopian tubes differentiates MRKH Syndrome from Mullerian Aplasia. However, others feel that they may essentially be the same disorder.

Vaginal Atresia

Absence of the lower portion of the vagina (replaced with 2-3 cms of fibrous tissue) but with normal upper portion. The cervix, uterus, Fallopian tubes and external genitalia are all normal. Normal breast development and pubic hair. Failure to menstruate. In the medical literature, Mullerian Aplasia and Vaginal Atresia are sometimes grouped together under the term ‘Congenital Absence of the Vagina’.

MURCS Association

A very rare condition characterized by several ‘associated’ developmental abnormalities present at birth. MURCS stands for M(ullerian) R(enal) C(ervico-thoracic S(omite) abnormalities. Affected individuals are females with Mullerian Aplasia, renal abnormalities including absent or mis-located kidney(s), and abnormalities of the spinal cord, ribs and/or arms due to improper development (dysplasia) of part of the embryo (cervico-thoracic somite).

True Hermaphroditism

A person who has both testicular and ovarian tissue is said, in old terminology, to be a true hermaphrodite. Hermes was the God of Intelligence and Wisdom, and Aphrodite was the Goddess of Beauty and Love. A true hermaphrodite may have a separate ovary and testis but more commonly has anovo-testis which is a gonad containing both sorts of tissue. This can be on one or both sides of the body. 60% of true hermaphrodites will have an XX karyotype and the remainder may have an XY karyotype or a mosaic (a mixture). The external genitalia may be ambiguous or female. There may be a uterus or (more commonly) a hemi-uterus (half uterus) on the side where there is ovarian tissue. The person may be raised female or male, and often undergoes genital surgery. The ovo-testis is usually removed because of the risk of malignancy.

‘XY Female’ Conditions

This rest of this page concentrates on XY conditions that are similar to AIS.

Biologically speaking, the pathway towards a female form seems to be the default for humans, while the path for development of a male foetus is more tortuous, and dependent on many different genes, each of which can be faulty. This means that there is a set of a fairly varied conditions in which a foetus with XY chromosomes develops as a baby girl.

Among these are:

  1. Failure of formation of testes due to a variety of reasons (i.e. Swyer syndrome or pure XY gonadal dysgenesis, XO/XY mosaicism, testicular regression syndrome etc.).
  2. Underdevelopment of cells in testes due to unresponsiveness to hormones from the pituitary gland (i.e. Leydig cell agenesis or hypoplasia).
  3. Enzymatic defects in testosterone biosynthesis (i.e. deficiencies of enzymes 5-alpha reductase, 17-ketosteroid reductase, 17-alpha hydroxylase, 3-beta hydroxysteroid dehydrogenase, 17-beta hydroxysteroid dehydrogenase etc.).
  4. Insensitivity of genital tissues to androgens (i.e. AIS).

In No. 1 the testes themselves fail to form properly. Nos. 2 and 3 come under the broad heading of a failure of androgen (male hormone) production by the testes. No. 4, AIS, is the most common, and therefore the best known of these conditions and is described on other pages of this site; so we will concentrate here on the other three types of condition. But first, we have to mention a much hated medical umbrella term and then say a bit about geting an accurate diagnosis.

‘Umbrella’ Term (MPH)

These various ‘XY female’ conditions have been grouped by doctors under an umbrella term called “male pseudo-hermaphroditism” (MPH). The male part of the term refers to the medical notion that the main determinant of the maleness is the presence of testes, and hermaphroditism refers to the apparent inconsistency of this notion in the face of an outwardly female patient. The pseudo- in the name acknowledges the fact that these patients are not really hermaphrodites, since they do not usually have both female and male gonads.

This term, which is a hangover from a time before modern genetic testing became available, is hated by most patients (see Terminology Debate). However, we mention this term here because there is no other commonly used term that covers all these conditions; and many affected individuals and families come to us quoting this term as their diagnosis. It would be a welcome move if doctors, researchers and patient groups could work together in finding a better term to substitute for MPH. The terms ‘XY female’ or ‘XY woman’ find favour with most of our group members, although we concede that this doesn’t cover the whole range because it excludes those who may identify as intersexed in terms of their gender.

Recently (2006) a new terminology has been proposed. See Terminology Problems on the What is AIS? page.

Note: Defects in synthesis, secretion or response to Mullerian Duct Inhibitory Factor or MIF (also known as Anti Mullerian Hormone, AMH) result in female genital ducts in men; while these conditions fall under the broad medical term of MPH, they are fundamentally different in that the affected individuals are otherwise normal men, i.e. there is a match between phenotype and genotype. Environmental chemicals can also cause some XY foetuses to develop as girls, but such conditions are not described here, as we concentrate on genetic causes.

Overlap with AIS

The AIS Support Group provides information and support to those with AIS and closely related conditions. It has ‘AIS’ in its name merely because the founder member was the mother of a child with AIS and we have never changed the name. We feel that a similarity of outcome, in terms of bodily features and gender identity, is more important than the precise nature of someone’s condition at a cellular level. And in most of the conditions listed above, the effects are very similar to those of AIS.

A family information officer wrote from a hospital overseas, requesting information on behalf of a family, as follows:

I have a family with a child who has been diagnosed as having Swyer syndrome. They have asked me to make contact with you to see if you can supply them with information about this syndrome. They are keen to have any information available. Of particular interest is the experience of other families – the baby is just 4 months old. The baby’s gonads have been removed and they are keen to find out about what to expect at puberty. Is it possible that you have another family on your books in _____ [country].

We replied:

Unfortunately we are only in contact with one family in ______ [country] and they have a teenage AIS daughter. But it is almost irrelevant which particular condition a youngster has (AIS, Swyers, 5 alpha-reductase deficiency etc.) in terms of getting useful support because it is the psycho-social ramifications that are so potentially huge, and these tend to be universally applicable across these conditions. So much so that whilst parents and doctors may focus their attention on the medical/physical/developmental aspects, these can be of secondary importance in the eyes of the young women affected compared to whether or not the adults around them appear to accept their condition, and to encourage truthful, open and full discussion, and contact with other affected youngsters.

So our advice to the family would be to ask their consultant what to expect at puberty but not to focus on this too much at this stage and to use the years until then to educate themselves fully regarding the psycho-social aspects. And to do this, it doesn’t really matter whether they are learning about the experiences of Swyers, or AIS, or….whatever…. because the same principles apply. And apart from attending group meetings, the best way for parents to appreciate the range of problems that youngsters with these conditions can experience as they grow up is to read the accounts in our newsletter.


Quite a large proportion of those who contact the group with a diagnosis of  “Partial AIS (PAIS)” turn out, on subsequent investigation, to have a related but distinct condition. All these conditions, including AIS, are rare and few doctors will have come across sufficient patients to enable them to fine-tune the diagnosis, especially since AIS is the most widely known of them and is therefore the most likely diagnosis to be considered first.

AIS is described relatively frequently in the medical literature as a condition in which the patient’s XY chromosomes and testes contrast with her female appearance and gender identity, while there is less literature describing the other conditions in these terms, as they are more rare. Maybe this leads some physicians to consider AIS as a more acceptable, and perhaps less stigmatising diagnosis than some of the alternatives?

Dr. Cathy Minto (see Recommended Clinicians) presented a paper at a recent (2000) congress and reported that of 47 ‘XY female’ patients seen at the University College Hospitals, 47% had an accurate diagnosis, 32% are considered inaccurate, 15% have been changed and 6% have unknown aetiology because pre-gonadectomy results are unavailable.

Importance of Correct Diagnosis

One of the many unfortunate aspects of a) secrecy and denial, and b) mis-diagnosis, in these conditions is the effect on other family members. The various conditions may have different modes of genetic transmission; and apart from the disastrous effects on the patient of paternalism and lack of information, other family members might well have a valid interest in whether the condition could manifest in their children. So they need accurate information too. This cannot happen if the whole thing is shrouded in taboo and/or ignorance.

An accurate diagnosis is also very important in governing treatment decisions. For example, in non-AIS conditions the body will be fully responsive to androgens and this may result in virilisation at puberty. In PAIS Grade 3 or higher, this virilisation either does not happen or is very weak, but in someone with one of the other conditions, and who identifies as a girl, this could occur and be very unwelcome. In the latter case, pre-pubertal gonadectomy (and avoidance of testosterone-based hormone therapy) would be indicated.

Reaching an accurate diagnosis depends on a careful assessment of all clinical and biochemical features. Tests will be carried out to determine whether there might be a problem in producing androgens or with the body’s ability to use them in masculinising the body.

We will now consider the various ‘MPH conditions’ in more detail.

1. Failure of Testes Formation

This is also known as “dysgenic pseudo-hermaphroditism” and can be thought of as a failure of the development of testes in the presence of XY chromosomes. Development of testes depends on a number of genes (one on the Y chromosome, another on the X chromosome, and several more on various autosomes or non-sex chromosomes).

Swyer Syndrome

Swyer syndrome, or “pure XY gonadal dysgenesis”, is the name given to a condition in which individuals possess a 46 XY karyotype and female external genitalia. Women with Swyer syndrome have no ovaries or testes, but have “streak” gonads that lack both germ cells and hormone-producing cells; they just consist of fibrous tissue. It is thought that the gonads may begin to grow in the foetus but then deteriorate, leaving behind the streaks. Or, it could be that a mutation inhibits the function of a portion of the Y chromosome, the portion that would cause the sexual organ tissue of the embryo to develop into testes.

Swyer individuals have a normal vagina and uterus (the so-called Mullerian structures). However, with neither ovaries nor testes there are not enough hormones to promote pubertal sexual development, and usually there is no breast enlargement or pubic and underarm hair. Swyer syndrome is often diagnosed when young adults are evaluated for delayed puberty, as menstruation does not occur naturally. Some individuals have a minimally enlarged clitoris. Hormone replacement causes increase in breast size and underarm and public hair, and menstruation is possible if the proper hormone regime is followed. In some cases, streak gonads develop tumours which produce hormones, thereby resulting in modest breast and public hair development and minor menstrual spotting. Removal of the streak gonads is carried out to minimize the risk of cancerous growths.

Individuals with Swyer syndrome have reported using a variety of hormone replacement therapies that include estrogen, and progesterone. Some have found adding low levels of testosterone to be helpful. Swyer individuals are not androgen-insensitive and therefore do respond to androgens such as testosterone. This therapy is initiated at the time of puberty.

Since Swyer syndrome women posses a uterus they can get pregnant, through implantation of a fertilized donated egg in an in vitro fertilisation procedure. As they lack ovaries, they do not ovulate.

Swyer syndrome may result from a deletion along the Y chromosome, or a mutation in the SRY, the sex determining region on the Y chromosome, or from a mutation in another gene that affects the function of the sex determining region genes on the Y chromosome. There is some evidence to suggest that Swyer syndrome is inherited, though it may also be the result of a new mutation. Swyer syndrome is estimated to occur in less than one percent of the population.

(The above section is based on text kindly supplied by a group member with Swyer syndrome.)

One of our medical advisers answered an enquiry from a group member with Swyer syndrome who was concerned as to whether she had a duty to inform her nieces of her condition (she preferred to keep it private if at all possible). Her neices do not have the condition but she was worried in case they might be carriers. He replied as follows:

It is extremely rare for Swyer’s syndrome to be inherited and to my knowledge, the familial form only occurs as sister pairs and does not pass vertically through a family. I can be fairly categorical therefore that your nieces will not be affected [as carriers] and that there is no reason why they should be informed of your condition.

We sought further information on her behalf from another of our advisers, an expert in genetics of intersex conditions, who replied:

Swyer syndrome is the eponym for what we classically regard as complete XY gonadal dysgenesis. In that scenario, inactivating mutations in the SRY gene may be found, but only in 15-20% of people [with the syndrome]. Whether carrier detection is possible all depends on whether there is a mutation which can be identified in yourself. You would need to see a genetic counsellor first of all and that would be arranged by your general practioner. A number of laboratories can screen for mutations in the SRY gene, including our own.

We have no idea what is the cause in the large remainder; work is ongoing looking at SF1, as the occasional patient has been found with a mutation in this gene. In our series we have not found a mutation in SF1.

SRY is on the Y chromosome and so can only be passed from father to son [XY child]. So nieces who are definitely known to be XX or definitely do not have gonadal dysgenesis clinically (for example have menses or are fertile) cannot either have the mutant gene or be carriers. What is puzzling about SRY mutations, however, is finding the same mutation in the ‘normal’ father of the affected Swyer subject or in the brother of the subject (as we have found recently). We do not know why these normal males did not develop Swyer, but things like incomplete genetic penetrance or somatic mosaicism have been invoked but without proof.

Just to add another level of complexity, XY gonadal dysgenesis can also be inherited as an X-linked disorder [the mechanism that applies in AIS] and some evidence [exists] from family studies of perhaps autosomal inheritance (see Williams Textbook of Endocrinology, 10th Edition). Even less is known about the genes in these types.

I end by emphasising again that genetic counselling is clearly more straightforward when the precise genetic abnormality is known. Even when an SRY mutation is found, it may not be that simple to counsel, as explained above. The best stopping off point if a person needs advice on these matters is to ask to see a clinical geneticist.

XO/XY Mosaicism

Turner syndrome is a condition in which a person has a single X sex chromosome and no Y chromosome. Anatomically, Turner syndrome patients are similar to those with Swyer syndrome, with a major physical difference being in height: Turner individuals are usually under five feet tall, while Swyer individuals are of normal stature.

Turner syndrome is very distinct from AIS, and is unlikely to mistaken for AIS. However, there are patients who have a mixture of 45,X and 46,XY cells in their bodies, resulting in a condition known as 45,X/46,XY mosaicism, or “mixed gonadal dysgenesis”, which has the potential to be mistaken for PAIS. As in PAIS, the external anatomy can be anywhere within a wide range from typically male to typically female. In some cases, a testis develops on one side of the body, and a streak gonad on the other, with a partial uterus on the side with the streak gonad.

Testicular Regression Syndrome

The testes disappear at a very early gestational age. The term Vanishing Testis Syndrome is generally used for the form of this where the regression occurs late in foetal life, and the genitalia are formed as normally male.

Some cases diagnosed as Swyer syndrome may actually be cases of testicular regression where the testes disappear at an extremely early gestational age. This could be so in cases of ‘Swyer syndrome’ with only a partly developed uterus, which strongly suggests that there was testicular tissue around in early fetal life, but alternatively this might happen before MIF can be produced, so the testes would vanish “without leaving a trace”.

2. Under-development of Leydig Cells

Leydig Cell Hypoplasia

Under normal circumstances the foetal testes accomplish two things: they produce Mullerian Inhibitory Factor (MIF) and they produce testosterone. In some cases, the cells that produce MIF (called Sertoli cells) work normally, while the cells that produce testosterone (called Leydig cells) do not develop properly. This condition is known as Leydig Cell Hypoplasia (hypoplasia means underdevelopment) and the individual develops under less or in some cases no testosterone, and consequently has a corresponding degree of feminization. Because the Sertoli cells are normal, and MIF is produced normally, they do not have development of uterus or Fallopian tubes.

There may be several causes for underdevelopment of Leydig cells, but it is often a consequence of a defect of the receptor for the Luteinizing Hormone (a pituitary hormone), and in these cases the condition is also called LH Resistance. The LH receptor is used for activation of Human Chorionic Gonadotropin (hCG), in other words, the hormone that comes from the placenta (chorionic) that is responsible for development of gonads (gonadotropin).

In contrast with AIS, the androgen receptor is quite functional. Androgens will therefore cause virilization, in both mild and severe cases of LHR. XY women with severe degrees of LHR will not produce any androgens at pubertal age so, unlike in AIS, the conversion of androgens to oestrogens (a process known as ‘aromatization’) does not occur as a means of effecting a natural feminizing puberty. They respond well to estrogens, however, and can develop pubic and underarm hair similar to unaffected women (because they also respond to androgens, unlike CAIS women).

It is worth noting that unlike AIS, LCH involves a defect on an autosome (not on a sex chromosome) and requires two mutated genes, one from the father and one from the mother. This has several repercussions. Unlike AIS, it is possible for XX women (who might have siblings with LCH) to also have LH Resistance. This results in infertility, but with development of uterus, ovaries, etc. It is also worth remembering that fertile brothers as well as sisters may be carriers. Because it is usually necessary for both parents to be carriers for someone to have LH Resistance, the condition is more likely when there is common ancestry between the parents.

3. Enzymatic Defects in Testosterone Biosynthesis

There are several enzymes that are part of the usual process of testosterone synthesis.

Some enzymes (e.g. 17-ketosteroid reductase, 17-alpha-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-beta-hydroxysteroid dehydrogenase etc.) facilitate the production of testosterone; and others (e.g. 5-alpha reductase) facilitate the conversion of testosterone to a stronger form that’s needed for full development of male genitalia.

So if any of these enzymes are not produced, then foetal masculinization does not occur and instead the baby develops as a girl with internal testes. In some cases, the enzymes work partially, and in these cases there is a variable degree of masculinization or feminization. The conditions also vary according to what happens at puberty, i.e. virilization, feminization, or ‘nothing’ (‘eunuchization’, if you like stigmatizing language).

Some of these enzymes, such as 17-ketosteroid reductase, 17-alpha-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-beta-hydroxysteroid dehydrogenase etc, are important for the development of both female and male reproductive organs, and may also be important for the development of the adrenal gland.

5-alpha-reductase Deficiency

5-alpha-reductase is an enzyme that converts the weaker testosterone into the more potent dihydrotestosterone (DHT). When this enzyme is deficient (a condition known as 5-alpha-reductase deficiency) the baby develops as a girl. However, at puberty testosterone production usually increases and is enough to cause virilization, so in such cases (where the child identifies strongly with a female role) it is advisable to perform a gonadectomy before puberty. On the other hand, there are cases where the child naturally migrates to a male role. Therefore, a conservative approach that incorporates listening to the child is imperative. 5-alpha reductase deficiency, unlike AIS, involves a defect on an autosome (not on a sex chromosome) and requires two mutated genes, one from the father and one from the mother.

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