Introduction

In 1938, Henry Turner described it for the first time in the journal Endocrinology. It was a group of 7 women between 15 and 23 years old. Those women showed a set of physical alteration and made him group them together in a new syndrome called TURNER'S SYNDROME.

There were three most typical features described by Henry Turner in those seven women: Infantile sexuality, Pterigium colli and elbow malformation or cubitus valgus.

These three features among others are still a reference for every doctor or scientist to describe TURNER'S SYNDROME.

Sixty-three years later we all know that this syndrome is relatively frequent. It appears in one of every 2500 newborn girls, consequently in approximately one of every 5000 births and in one of every 15 spontaneous abortions.

Nowadays, we also know that this syndrome has a well-defined chromosomal base. In 1959 Ford and col., made the first chromosomal analysis to women with Turner's syndrome, they found they all showed a single X chromosome instead of two. It was proved that the TURNER'S SYNDROME was the result of a total or partial absence of the second sexual chromosome in human being.

All human beings have 46 chromosomes in our cells, 44 of them are shared by men and women, these are called AUTOSOMES. The other two are called SEXUAL, they are chromosome X and chromosome Y. Except in rare occasions, women have two chromosomes X (we are XX) and men have a chromosome X and a chromosome Y (they are XY). The genes which are responsible of the development of the male sexual features are located in the chromosome Y. However, girls with TURNER'S SYNDROME have in a part of their cells a unique Chromosome X instead of two (they have totally or partially lost the second sexual chromosome) that is why it is said they are 45,X instead of 46,XX.

If you look carefully at these photographs, you will understand the former concepts in a better way:

Example of a Karyotype from a 46,XX woman

Example of a Karyotype from a 45,X Turner Woman

MOST CHARACTERISTIC FEATURES OF THE TURNER'S SYNDROME

The absence of the second sexual chromosome in human beings is the origin of a group of physical alterations that distinguish Turner's syndrome and could be classified as follows:

At the birth moment

This syndrome only affects girls. The presence of only one chromosome X instead of two provokes the resultant sex to be always the same: female. So, it's very rare and exceptional in male sex. When this happens (a male patient) chromosome Y is usually implied in a big part of the organism cells. In male patients some of those typical features like small size can appear joined to another syndrome with a different genetic origin called NOONAN SYNDROME.

• At birth, girls with Turner's syndrome weigh less and are shorter in height than the rest of newborn girls. Even during the pregnancy, the doctor could appreciate a slow growth in the girl.

• They are usually born with LYMPHOEDEMA of the dorsal surfaces of the hands and feet which usually regresses by late infance.

• These girls usually have a wide and short neck. Sometimes an excess of skin can appear, it is referred to as "wings", which join the neck with the collar bone, this phenomenon is called Pterigium colli. Henry Turner defined it as a "neck webbing". It can be rectified by surgery.

• The thorax is broad with the mammary glands and the breast more separated than usual.

• The ears are slightly turned, the hair has got its growth line downwards in the back of the head. Although they draw our attention, all those features are not dangerous for the girl's health. Of course, they are aesthetic features and so that they may be corrected by surgery if the parents or the girl decide it.

• It is very important to emphasize that the nervous system is not affected, so, this syndrome doesn't provoke mental disorder. These girls are not different from the other girls of the same age, except they have some physical problems.

• They can show other much more important malformations such as cardiac or kidney malformations between others.

Between the age of two and adolescence

As years go by, it is more and more obvious not only the girl's short height or her wide trunk but her separated breasts. When the girl is five years old, freckles and spots appear in the trunk. The forearm is situated towards the outside part from the elbow (cubitus valgus).

Because they have a shield thorax and short height, these girls generally look robust and they have got some kind of shortness in their legs compared to the trunk.Puberty doesn't usually begins spontaneously even not when they shoot up in a related process. As a result, these girls show a more infantile physical appearance than the rest of girls. More and more Turner's features are strongly distinct, especially the short height which is more evident.

But, of course, we can also find girls who don't show almost none of the previously detailed alterations. Though this isn't very clear, it is believed that he reason for this is the chromosomic error in the girl because it is not the same having lost a whole chromosome X than only a part of it. And it is not the same having 1% of 45,X cells than a 99%, at least apparently because there are exceptions.

Adult age

Even though they have been treated with female hormones since they were girls, these women have little developed ovaries (ovaries in bands) or they can be sterile in the adult age. The short height and sterility are the most frequent and traumatic features of the syndrome. They are treated with growth hormones since they are twelve or thirteen, but the definitive height is below the average, however, we have to take into account their parents' height.

WHEN AND HOW TO DIAGNOSE THE SYNDROME?

The doctor easily detects Turner features from the birth moment, but it is not always like this because there aren’t two identical Turner girls. Turner girls can present all alterations we have mentioned in the former section (short height, winged neck, elbow malformation etc) or none of them. That is why it can happen the doctor diagnoses the newborn girl without the least difficulty or it can happen that nobody notices anything strange until the puberty. There are even cases of women who have been diagnosed the syndrome in their adult age, when they want to have a child and they cannot. In any case, it is very important the chromosomal study to be realised as soon as possible, since a delay in the diagnosis implies a delay in the treatment.

At present, the diagnosis of the syndrome is more precise than some years ago. It consists on a study of the karyotype (a study of the chromosomes) from a little sample of blood. These studies indicate us that a percentage of Turner women have a unique chromosome X in their cells (45,X) instead of two. Others are mosaic women, that is to say they have normal cells (46,XX) and they also have cells which have lost a chromosome X (45,X).

Very rarely, cells with the chromosome Y or rests of it could appear combined with 45,X cells. In these cases, it is very important an early MOLECULAR diagnosis because there is a high probability of developing a tumour in the ovarian rests named GONADOBLASTOME. When the rests of the chromosome Y are detected in girls with Turner syndrome, the removal of gonads is generally advised.

The appearance of little fragments or chromosomal rings that can proceed from the chromosome X or the chromosome Y is not very frequent. This karyotype joined to the former one can be the most worrying in the syndrome (not always), as the presence of little chromosomal rings derived from the chromosome X is related with mental illness.

Talking about this subject, we have to emphasize two fundamental facts: first, the presence of those rings in Turner Syndrome is exceptional; second, it is the only case where the syndrome appears with mental illness.

THREE TECHNIQUES MUST BE REALISED FOR A GOOD GENETIC STUDY

It is very important an early diagnosis of the syndrome. As we have stated before, the diagnosis mostly often depends on the clinical expression of the syndrome, so, it will mainly depend on the discernment and preparation of the doctor to detect the girl has more or less signs that betray the syndrome. Anyway, even in expert hands, there are some cases in which the diagnosis is more difficult due to the alterations presented by the girl, which are very sutile. In all cases and especially if the girl’s growth is altered, the doctor must ask for a study of the karyotype which will confirm or discard a chromosomal anomaly. Although physical signs can be very clear and plentiful, it is absolutely essential to make a genetic analysis. In our opinion, a good genetic study must include three steps:

1. A study of the chromosomes through the realization of a karyotype. This technique is the one usually employed in hospitals and it is done from a little sample of blood. It consists on the classification of the patient’s chromosomes. If the patient shows a unique chromosome X in all or in part of her cells or if one of the chromosomes X is altered, we can define it as Turner syndrome.

2. A detailed study of the chromosomes through the Fluorescent In Situ Hybridization technique (FISH) with specific probes for chromosomes X and Y. When the clinical suspicion exists, we must extend the genetic studies with this technique. Investigation works that have been made in our lab prove that it is necessary to apply molecular biology techniques for a good diagnosis. The routine use of the FISH technique allows the detection of mosaics of a very low percentage and it also allows the detection of the origin of small chromosomal fragments, rings, deletions, chromosome Y derivatives etc.

3. A molecular study of the chromosome Y through PCR (Polymerise Chain Reaction). This technique allows the detection of the presence of small fragments derived from the chromosome Y, even if they are very small. When small or actually diminutive chromosomal fragments of an unknown origin have been detected through the study of the karyotype, it is essential the application of the PCR technique.