Clinical syndromes

The X chromosome favours development of female characteristics but full development is only possible if there are two such chromosomes. Any alteration in this number leads to abnormalities.

Development of the testis is entirely dependent on the presence of a Y chromosome. The testis, in addition to forming testosterone, which aids the development of male characteristics, produces a Müllerian inhibitory factor. Both male and female fetuses initially have both Müllerian and Wolffian systems.

In the absence of a testis, the whole Müllerian tract will develop, but curiously this does not depend on the presence of ovaries. These interrelationships result in a number of clinical syndromes with variations in individual cases.

Investigations of genetic defects

In all cases, it is important to obtain a family history as complete as possible. Siblings and relatives of patients may give a history of amenorrhoea and infertility.

Laboratory studies

Turner’s syndrome (Sex Chromosome Deletion: X)

The commonest chromosomal pattern is 45XO. Not all features of the condition are always present. In patients who are mildly affected, there may be a partial deletion of the X chromosome (Xx) or mosaicism (XO/XX). In such cases, normal ovaries can develop and menstruation can occur.

In males some of the somatic stigmata of Turner’s may appear. This may be due to partial deletion of the Y chromosome – Xy, or to mosaicism – XO/XY.

Klinefelter’s syndrome (Sex Chromosome Acquisition: X)

There is a Y chromosome with an increase in the number of X chromosomes. The commonest abnormality is 47XXY. The phenotype is male. The clinical features vary but the majority have hypogonadism and infertility. Facial hair is scanty and pubic hair has a female distribution. Gynaecomastia can also be present. Mild developmental problems and learning difficulties can occur but the vast majority of individuals have normal intelligence. There is an association between mental impairment and the number of X chromosomes.

Super-female (Sex Chromosome Acquisition: X, Sometimes at Both Stages of Meiosis)

This is a term sometimes used when the patient possesses extra X chromosomes but no Y chromosome. The pattern may be XXX, XXXX or even XXXXX. Physically these individuals are normal females, but the important point is that there is usually some mental impairment and the degree of this increases with each extra X chromosome. Diagnosis is made by chromosomal analysis.

Complete androgen insensitivity (cais)

This condition was previously known as testicular feminisation and may be mistaken for a sex chromosome abnormality. The chromosomal pattern is 46XY; however, there is insensitivity of the androgen receptor to respond to androgenic stimulation. As a Y chromosome is present, the testes form normally, producing anti-Müllerian hormone (AMH) and testosterone. AMH causes the regression of the Müllerian ducts (see Chapter 1), and the uterus, fallopian tubes and upper part of vagina therefore do not form. As the tissues are insensitive to androgens, the lower genital tract fails to virilise and a short vagina is formed. The patient is phenotypically female. Usually the diagnosis is made in early adult life when the patient complains of amenorrhoea.

Patients with CAIS usually inherit it from their mother in an X-linked pattern, but new mutations are also common.

Most carriers are unaffected, but some may show scanty pubic and axillary hair and have delayed menarche.

Until full growth is achieved, no therapy should be attempted. After puberty and fusion of epiphyses, the gonads should be removed surgically. This is a precautionary measure in view of the increased incidence of tumours in such gonads. Following this treatment, the patient is liable to have menopausal symptoms and should be given oestrogen replacement therapy for symptom control and for skeletal and cardiovascular prophylaxis until age 50 years at least. As the uterus is absent, progesterone is not required.

All of these foregoing syndromes, whether genetic or not, can pose social, psychological and sexual problems. The patient may have to make a great deal of mental adjustment and in such cases sensitive counselling will be required. Karyotyping and referral for genetic counselling should be considered.

Partial androgen insensitivity can also occur. A variety of clinical features occur, but ambiguous genitalia is a common presentation.

Congenital adrenal hyperplasia (cah)

This is an abnormality of cortisol production that can affect both male and female infants. The commonest enzyme deficiency is of 21-hydroxylase. The adrenals also produce mineralocorticoids and steroid hormones, and deficiencies of one pathway lead to excess production in other pathways. The severity of the enzyme deficiency can vary and will lead to different clinical conditions.

Adrenal dysfunction is due to congenital deficiency of the enzyme 21-hydroxylase. It should be detected and treated at birth.

Abnormalities of the ovary

Absence of one ovary may occur in an otherwise normal woman. Before operating on one ovary, always look at the other.

With ovarian dysgenesis, the ovaries appear as ‘streaks’. In place of the ovary there is a strip of whitish connective tissue continuous with the ovarian ligament. It may contain vestiges of a rete, and occasional cells which may be of germ cell type, but no follicles. These ‘streak’ ovaries are sometimes the seat of tumour growth, such as gonadoblastoma and dysgerminoma, and should always be removed.

Abnormalities of the fallopian tube

Absence is rare. The tube may be imperfectly developed.

This illustration shows a condition in which the proximal half of the left tube has failed to develop. The right adnexa are normal. All of these conditions are rare, but their importance lies in their association with infertility.

Absent or rudimentary uterus

The uterus consists of two nodules connected by a membrane (‘ribbon’ uterus). The other structures are normal. If a cavity exists in a nodule, cryptomenorrhoea (concealed bleeding) and dysmenorrhoea may arise and retrograde flow may lead to pelvic endometriosis.

This can be associated with atresia of the vagina (Mayer–Rokitansky syndrome).

Double uterus (bicornuate uterus)

One or other variant of this condition is the commonest abnormality of the genital tract. It is due to failure of fusion of the Müllerian ducts, or failure of one to develop. There are a number of terms that describe the abnormality.

Uterus didelphys

Double uterus and cervix, usually with double vagina.

Two uterine corpora with two cervices. Both cervices need to be sampled at cervical screening. There are occasional reports of discrepancies with vaginal assessment during labour due to unrecognised double cervices.

Bicornuate uterus or uterus bicornis

Note the ligament, which may pass from rectum to bladder. There is a cleft present at the fundus.

Uterus with accessory horn

The accessory horn has no cervix. If it menstruates, cryptomenorrhoea will follow. Spermatozoa can reach the horn by crossing the peritoneal cavity, and pregnancy can occur within a rudimentary horn.

Arcuate uterus

The cavity has an indentation at the fundus.

This is probably the mildest form of uterine abnormality.

Septated uterus

The uterus appears normal externally, but the cavity has a septum.

Uterus unicornis

One Müllerian duct has failed to develop.

All of these abnormalities may be associated with obstetric implications. These include increased rates of infertility, miscarriage, preterm delivery and malpresentation. This, however, depends on the extent of the abnormality, and many women will have uncomplicated pregnancies.

Ectopia Vesicae

Is an extreme defect seen in the newborn, but one which is susceptible to surgical treatment. There is failure of development of the symphysis pubis, mons, lower abdominal wall and anterior wall of the bladder. The tissues exposed are the posterior wall of the bladder, the ureteric orifices and the floor of the urethra.

Congenital abnormalities of cloacal origin

These are due to failure of the cloacal septum to divide the cloaca perfectly into hindgut and urogenital sinus. The less serious degrees may persist unnoticed in adults as some form of ectopic anus.

The vestibular anus

Patients with these abnormalities can defecate through the vestibule or vagina, apparently without suffering from incontinence.

The vaginal anus (very rare)

In all of these vulval abnormalities, infection is a problem – of the urinary tract in ectopia vesicae, and of the genital tract in the other two.

Genital abnormalities

The results of these conditions as they relate to gynaecological practice have already been mentioned in the section dealing with amenorrhoea.