Genetics

1. THE DOCTOR HAS TOLD ME MY DAUGHTER HAS TURNER SYNDROME, BUT, WHAT IS IT?

Turner syndrome consists on the total or partial loss of one chromosome X. This means that instead of two sexual chromosomes these girls have only one chromosome X, at least in a part of their cells. But, generally, having a unique chromosome X doesn’t provoke severe alterations neither physical nor mental. A Turner girl is a normal girl but a bit shorter, with growth problems.

This syndrome has nothing to do neither with Down syndrome nor with other syndromes. If we compare a girl or a boy with down syndrome to any man or woman with Turner, we can observe they have a chromosome 21 more and Turner girls have a chromosome X less. That is the only similarity between them, both syndromes have a chromosomal abnormality but no more.

• Karyotype 46,XX

• Karyotype 46,XY

• Karyotype 45,X

2. DOES TURNER SYNDROME EXIST IN BOYS??

We generally can say that, except in rare occasions, Turner syndrome does only affect women. But we can’ t say without doubts it doesn’t exist in men. The exception is found in boys who combine 45,X cells and 46,XY cells. So, they have characteristic male cells (those which are 46,XY) but they also have typical Turner syndrome cells (45,X).

Depending on the embryo time when 45,X cells have appeared, on the kind of organ affected by the mentioned cells and on the chromosome Y being altered or not, the resultant child can be a boy or a girl both with the characteristic features of the syndrome.

In the following paragraph, we show you the results of some molecular tests of a 45,X/46,XY Karyotype which could become a boy or a girl. The presence of the chromosome Y in these patients doesn’t always imply the patient to be a boy. SEE MOLECULAR RESULTS.

3. IS TURNER SYNDROME INHERITED?

NO. Like any chromosomal syndrome, if parents show a normal karyotype it is not inherited. So, we can say it has happened by chance, it is not anything we can avoid and it is not the result of something that has happened during the pregnancy.

4. WHY DOES TURNER SYNDROME APPEAR? WHAT IS THE ORIGIN?

There are two theories that try to explain this chromosomal anomaly (the loss of one of the sexual chromosomes):

A.- The “MEIOTIC” theory says that during the formation of the ovule or sperms (gametogenesis) some of them could have suffered an error and for this reason they carry a sexual chromosome less. If the ovule or the sperm have suffered this chromosomal loss, the person formed from the fertilisation will carry this chromosomal error.

B.- The “MITOTIC” theory assures that the loss of one of the chromosomes is not produced in the gametes (ovule or sperm) but it is originated later, during the first period of the embryo growth (in the first gestation weeks). The most recent investigations support this last theory not the first.

5. IS TURNER SYNDROME VERY FREQUENT?

It appears in one of every 2500 newborn girls or in one case of 5000 births and in one of every fifteen spontaneous abortions. The majority of spontaneous abortions are 45,X while those who are born usually show 45,X and 46,XX cells at the same time.

6. ARE THERE ANY POSSIBILITIES OF HAVING ANOTHER TURNER DAUGHTER?

As we have previously commented, Turner syndrome is not inherited, therefore, al mothers have the same possibility of having a Turner girl; it is one of every 5000. The fact of having a Turner girl yet doesn’t increase the probability of having another one; they are two independent facts, unless any of the parents suffer from an alteration in his/her sexual chromosomes, if this happened they should consult their doctor.

7. WHEN AND HOW TO DIAGNOSE TURNER SYNDROME?

It can be diagnosed in the moment of birth and sometimes later, if the girl hasn’t got important physical alterations. The doctor detects a set of alterations that make him suspect from the chromosomal anomaly. That is when he must ask for a genetic study called karyotype, which consists on a study of the chromosomes. The karyotype is usually done from a little sample of blood and it generally takes four or five days to be finished.

8. WHAT OTHER TECHNIQUES CAN BE USED TO DIAGNOSE TURNER SYNDROME (APART FROM THE KARYOTYPE)?

The most recent investigations defend the combined use of cytogenetic and molecular techniques (karyotype, FISH and PCR). In our opinion, a good genetic study must include three steps:

1. A study of the chromosomes through the realisation of a karyotype. This technique is what is usually employed in hospitals and done from a little sample of blood. It consists on the obtaining, tinction and classification of the patient’s chromosomes. If the patient shows only one 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 Hybridisation (FISH) technique with specific probes for the chromosomes X and Y. When the clinic suspicion exists the genetic studies must be extended by this technique. The investigation works that have been made in our lab show it’s necessary to apply molecular biology techniques for a good diagnosis of the Turner syndrome. The routine use of the FISH technique allows us to detect mosaics of a very low percentage and also the origin of little chromosomal fragments, rings, deletions, derivatives of the chromosome Y etc.

3. A molecular study of the chromosome Y through PCR (Polymerise Chain Reaction). This technique allows detecting the presence of little fragments derived from the chromosome Y even if they are tiny. When these little or tiny chromosomal fragments from an unknown origin have been detected it is essential the application of the PCR technique.

9. WHAT OTHER CHROMOSOMAL ALTERATIONS GIVE RISE TO TURNER SYNDROME (APART FROM THE 45,X KARYOTYPE)?

One of the best-known karyotypes is the 45,X, consequently, a whole chromosome X has been lost, although the most recent studies affirm that it isn’t as frequent as imagined some years ago.

Another very frequent karyotype is the combination of two kinds of cells: a percentage of 46,XX cells (normal ones) and other part of 45,X. The percentage of each cellular type varies from one girl to another. For example, we can have 99% of normal 46,XX cells and only 1% of 45,X cells or, on the contrary, 99% of 45,X and 1% of 46,XX. The combinations could be varied.

There are other kind of alterations such as the combination of 45,X and 47,XXX cells; 45,X/46,XX/47,XX cells and more. But maybe the most dangerous alterations, although very little frequent, are those which own little or even diminutive chromosomal fragments from an unknown origin. These fragments are usually derived from a chromosome X or a chromosome Y. In one case or another they must be studied because they can originate mental illness when they derive from a chromosome X. If they derive from the chromosome Y, they can provoke one kind of cancer in the gonads called gonadoblastome. The risk of developing this cancer is avoided by the removal of those formerly mentioned gonads, which, otherwise, weren’t functional yet.

10. IS IT TRUE TURNER GIRLS ARE MORE OR LESS AFFECTED DEPENDING ON THEIR KARYOTYPE?

We can say it is true in some cases, but it isn’t always like this. There are contradictory studies referring to the question. Some girls are less affected than others are and the reason isn’t well known.

It is known that the presence of little chromosomal fragments derived from the chromosome X can provoke mental illness. It is also known that the presence of rests of the chromosome Y increases the risk of the development of gonadoblastome. But other features are more difficult be assigned to a concrete chromosomal alteration. For example, we tend to think that a Turner mosaic girl (45,X/46,XX) would present more subtle alterations than other girl with all her 45,X cells, that is because the Turner mosaic girl has got a combination of healthy cells and Turner cells. But the current studies indicate this is not totally correct. The more or less affected aspect of a Turner girl will depend on the kind of cells and the organ where these mentioned cells are located. So, there are some cases of 45,X girls (in their blood) who don’t show any kind of visible alteration, except for the short height and low sexual growth. However, there are other cases where the percentage of 45,X cells is minimum and, in contrast, the girl has a severe Turner look.

The most recent investigations into the syndrome prove that we can’t exactly predict the phenotypic alterations in Turner syndrome from a karyotype exclusively done in blood. The study of the chromosomes in blood doesn’t exclude a different karyotype in other organs.

11. ARE THERE ANY ADVANTAGES IN AN EARLY DIAGNOSIS?

Many. The sooner we diagnose the alteration, the better her specialist could treat the girl. This implies she could be treated with the growth hormone and with the sexual hormones when the doctor considers it is the right moment. Everything that tends to smooth Turner features in the girl will help her to relate to other people naturally.

12. DOES THE KARYOTYPE AFFECT THE GIRL’S PERSONALITY?

The psychological studies indicate the existence of a set of features that characterise women with Turner syndrome. Some authors even defend the existence of personality features depending on the paternal origin of the chromosome X. If the chromosome X of a Turner girl with a 45,X karyotype comes from the father, it will have some features which can make her different to those girls who have inherited it from the mother. This phenomenon is known as imprinting, but this is not totally proved.

If you want more information about this question, just click here:

Nature 1997 Jun 12;387(6634):705-8

Not all investigators accept these theories. It is believed that it is more reasonable to think about the hidden mosaicism in other organs and therefore undetectable in blood, because it has great importance between the features of a woman with Turner syndrome:

Hum Genet 1996 Jul;98(1):29-35

Nature 1997 Dec 11;390(6660):569

Clin Genet 2000 Sep;58(3):201-8

Generally, we can say that girls with Turner syndrome have a normal intellectual development although they show difficulties to understand the numeric and spatial concept. Due to this, they tend to present problems with Mathematics and Crafts. The cause of these difficulties in the spatial perceptive processing isn’t very clear.

Girls with Turner very frequently show a delay in their emotional maturity clearly related to the overprotection they receive from their parents. They can also present, when they are children, problems of social behaviour or attention. Some of them find it impossible to constitute stable couples.

Other characteristics when they are little girls are problems of social behaviour and attention (they are usually hyperactive, excitable, they have problems in their social and school relationship with a low self-esteem. The psychological phenotype is usually very complex but it widely varies from a Turner woman to another. A mature Turner woman tends to have a serene personality.