Turner syndrome: can it be detected prenatally?

Turner syndrome is a genetic disorder described in 1938 by H. Turner, whose genetic basis was known in 1959 by C. E. Ford, determining that it is an alteration in the sex chromosomes that affects women. In this article we tell you what this syndrome consists of and how it is possible to detect it prenatally.

What is Turner syndrome?

Before we begin, we briefly recall the information included in other posts such as Genes and chromosomes: how do they determine our life and health? Humans have 23 pairs of chromosomes, one inherited from each parent, for a total of 46 chromosomes. The first 22 pairs of chromosomes are called autosomal chromosomes and the 23rd pair are the sex chromosomes, and they determine the biological sex of an individual, being XX in the case of women and XY in the case of men.

The loss of one of the chromosomes of either pair is called monosomy. Turner syndrome is a syndrome that only affects females, as it is due to the total or partial loss of an X chromosome. Turner syndrome is considered the only monosomy compatible with life. It is estimated to have an incidence of approximately 1 in 2,500-3,000 newborn girls, although the incidence at the time of fertilization is higher and affects about 1-2% of all conceptions.

In approximately 50% of cases there is a total loss of one of the X chromosomes, which is known as monosomy of the X chromosome or classic Turner syndrome. The remaining patients present a mosaic monosomy X (only a percentage of the cells present the alteration) or structural rearrangements in the X chromosome with or without mosaicism. Within the possible structural rearrangements we differentiate:

• X isochromosome. It is the most common structural rearrangement, in which the X chromosome consists of 2 short or 2 long arms.
• Ring chromosome: occurs when the ends of the X chromosome break off and fuse together to form a ring chromosome.
• Xp or Xq: when a partial deletion of the short arm (p) or long arm (q) of the X chromosome occurs.

It is important to note that in about 6-11% of cases of Turner syndrome there is mosaicism with the presence of the Y chromosome in one of the cell lines. Identifying these cases is of special relevance, since they have a higher risk of developing gonadoblastoma, a type of tumor affecting the gonads.

How does Turner syndrome occur?

Turner syndrome can occur for several reasons:

Genetic alterations in the gametes

In general, it usually occurs due to a problem in the formation of the gametes, that is, the egg or sperm. For these cells to form, a process called meiosis occurs, whose final objective is to obtain cells with a single copy of the chromosomes, that is, 23 chromosomes in total, so that when fertilization occurs, the embryo has 23 chromosomes from each gamete, giving a total of 23 pairs of chromosomes, one inherited from each parent.

During meiosis, a process called disjunction occurs whereby the homologous chromosomes of each pair separate, so that each daughter cell has one copy of each chromosome. Well, if a failure occurs and nondisjunction occurs, these homologous chromosomes will not separate, so that one daughter cell will receive two copies of that chromosome, while the other daughter cell will receive no copies. This can also occur in sex chromosomes, giving rise to eggs (female gamete) or sperm (male gamete) that do not have sex chromosomes. If fertilization of these gametes occurs, the resulting zygote may acquire a copy of the Y chromosome, which is not compatible with life, or acquire a copy of the X chromosome, resulting in monosomy X or Turner syndrome.

Error in cell division during gestation

Mosaic Turner syndrome has a different origin. In these cases, after fertilization an error occurs in the division of the embryo's cells at an early stage of development, resulting in cells with monosomy X. This error is a non-disjunction as well, but occurs during mitosis. In this case, the cells with the alteration continue to divide and all the cells that come from it will have the same alteration, while the rest of the cells of the embryo will have the normal pair of sex chromosomes. In these cases, the affected women will have two different cell lines, some with the alteration and others without.

Family history does not seem to be a risk factor, so it is considered unlikely that this syndrome will recur in families, although it is always advisable to consult a genetic counselor to study the specific case and communicate the information in an appropriate manner.

Symptoms of Turner syndrome

The external phenotype or appearance of women with Turner syndrome is very variable, for this reason there are no clinical diagnostic criteria and it will always be necessary to confirm the diagnosis by performing a karyotype. In addition, it is important to note that not all possible manifestations will appear in the same person and that certain symptoms will depend on age. Despite the variability of phenotypes, there are typical clinical signs and symptoms of Turner syndrome:

• Short stature, which is usually about 20 cm less than average.
• Gonadal dysgenesis which may be associated with other abnormalities such as lack of menstruation and infertility.
• Other frequent physical features in women with this syndrome are:
• Wide and webbed neck
• Edema on the back of the hands and feet.
• Low-set ears
• High and narrow palate
• Delayed growth
• Low hairline implantation

In addition, this syndrome is also associated with other complications affecting different parts of the body.

• About 30-45% of patients may have congenital heart disease due to abnormalities in the structure of the heart, mainly narrowing of the aorta.
• Arterial hypertension of the essential type, i.e., not due to any other apparent cause. The incidence of this symptom increases with age, and it is estimated that up to 60% of women with this syndrome present hypertension.
• Nephrourological alterations in approximately 25-40% of patients. Structural alterations of the kidney, urinary tract or renal blood vessels are common. Although they rarely lead to renal failure, they can increase the risk of recurrent urinary tract infections.
• Metabolic disturbances. Between 15-30% have hyperthyroidism and there is a higher incidence of diabetes due to increased insulin resistance, which in turn is related to increased risk of obesity. Autoimmune endocrine diseases such as Hashimoto's thyroiditis or Graves' disease are also more frequent.
• Digestive alterations that may cause inflammatory bowel disease such as Crohn's disease or ulcerative colitis.
• At the auditory level, the presence of otitis is common during childhood, due to alterations in the structure of the inner ear. Sensorineural hearing loss is also common, so some patients may require hearing aids.They generally present an intellectual development within the average, being able to live an independent life in adulthood. However, in a small percentage there is a greater tendency to present learning deficits, especially in non-verbal areas such as mathematics or drawing, and they have a higher risk of developing attention deficit hyperactivity disorder. Their prognosis is generally good, although life expectancy may be somewhat lower than in the general population due to complications secondary to the syndrome.

Treatment for patients with Turner syndrome

Generally, affected girls need the medical attention of several specialists. Regular check-ups together with appropriate medical care make it possible for women to lead an independent life in most cases.

Although treatment will depend in each case on the symptoms and complications that occur, there are two therapies that are used in the vast majority of cases:

• Growth hormone: to increase the speed of growth and therefore their final size. It usually starts at 3 years of age and it is essential that the treatment is properly followed.
• Estrogen therapy: used to induce puberty, around the age of 12.

When is Turner syndrome detected?

As we have seen, it is a syndrome that causes alterations in growth and development, so it is essential to detect it as early as possible, so that preventive measures can be taken that can delay the onset of complications or treat them appropriately.

With the introduction of noninvasive prenatal testing, it is becoming increasingly common to detect Turner syndrome prenatally. In other cases, ultrasound findings such as cardiac or renal malformations, increased nuchal translucency, among others, may be indicative of Turner syndrome. In any of these cases, the syndrome can be diagnosed prenatally by performing invasive tests such as amniocentesis.

If it is not detected during the prenatal period, it is usually diagnosed during childhood due to the presence of the symptoms previously described. There are some rare cases in which the diagnosis has been made during adolescence or even adulthood, when presenting very mild signs of the syndrome. At Veritas we are committed to health care from the very first moment. That is why we offer myPrenatal, the most complete non-invasive prenatal screening with which your doctor will be able to evaluate the risk of the fetus to present common chromosomopathies from the 10th week of gestation. If you want more information, do not hesitate to contact us.