Characterizing Turner syndrome is a "numerical or structural alteration of the X sex chromosomes: some patients lack an X chromosome in every cell of their body and in only a portion; others have a structurally altered and defective second X chromosome; others still they have cells with only one X chromosome and cells in which, instead of a second X chromosome, there are portions of the Y chromosome (ie the sex chromosome that identifies the male sex).
Turner syndrome is typically responsible for short stature and failure to develop the ovaries; moreover, it is very often associated with congenital heart and kidney defects and various physical anomalies.
Turner syndrome cannot be cured; however, patients can count on various symptomatic treatments, capable of stemming the main consequences of their condition.
Turner syndrome is also known as Ullrich-Turner syndrome or monosomy X and with the alphanumeric abbreviation 45, X.
Epidemiology: How common is Turner Syndrome
Statistics show that one in every 2,000-2,500 women is born with Turner syndrome.
In fact, this genetic disease is more common than the above, but in most cases it causes miscarriage or death at birth.
Did you know that ...
According to some estimates, Turner syndrome is responsible for 10% of total miscarriage cases in the United States.
human and the complex of genes constituting the latter.In a healthy human being, there are a total of 23 pairs of chromosomes; one copy of each pair is of maternal origin (ie derives from the mother), while the other copy is of paternal origin (ie derives from the father).
Of the 23 pairs of chromosomes that make up the human genetic patrimony, a pair - to be exact the 23rd - is decisive for the sex of the individual (sex chromosomes), while the remaining 22 pairs affect all the other characteristics and functions of the body. human (autosomal chromosomes).
To understand Turner syndrome, attention needs to be focused on the sex chromosomes.
The couple of sex chromosomes present in the woman is different from the couple present in the man: the woman has two chromosomes called X, while the man has an X chromosome and a chromosome defined as Y.
The correct number of sex chromosomes is fundamental for the well-being, health and proper development of the human being; the presence or absence of a sex chromosome, either X or Y, in fact, always causes profound consequences.
In the same way, for the health and the correct development of the individual, it is essential that the sex chromosomes have an appropriate structure; the lack of chromosomal portions, even minimal ones, in fact, involves important biological dysfunctions.
Turner Syndrome: Pathogenesis
The chromosomal alteration characteristic of Turner syndrome may be the consequence of:
- An error during the formation process of one of the sex cells (gametes) from which, through their union, the sick person originated. This error, which consists of a non-disjunction phenomenon, leads to the generation of a sex cell with an altered patrimony of sex chromosomes.
In this specific situation, the chromosomal alteration is the result of an anomalous event that occurred before conception; this means that the product of conception will maintain the aforementioned alteration in every cell of the organism.
or of:
- An error during the cell division process of the fertilized egg. Again, it is an error that alters the number of sex chromosomes of a cell; however, unlike the previous situation, the chromosomal alteration is limited to the cell line which descends from that cell that became the protagonist of the aforementioned error (the organism that will be born will therefore have cells with a normal chromosomal profile and cells with an altered chromosomal profile).
In both circumstances described above, Turner syndrome is not inherited in nature (although the sex cells belong to the parents, the alteration that distinguishes one of them is only the result of a sporadic abnormal event).
Turner Syndrome: Monosomy, Mosaicism and other chromosomal kits
Through their studies, the experts observed that there are at least 4 distinct chromosome sets associated with Turner syndrome.
The most common chromosomal set (50-60% of cases) is that characterized by monosomy X; monosomy X indicates the absence, in each cell of the patient's body, of a second X chromosome.
Monosomy X is explained by a "chromosomal alteration which occurred even before conception and concerning the sexual cells whose encounter led to the birth of the sick individual.
The second most widespread chromosomal set is that characterized by a mosaic phenomenon, such that only a part of the cells of the diseased organism has one X chromosome, while the remaining part has two.
Mosaicism is typical of when the chromosomal alteration from which the disease arises occurs after conception, in a phase of the process of dividing the fertilized egg.
The third possible chromosomal set is that marked by the presence of a normal X chromosome and an X chromosome altered in structure; known as a ring chromosome or isochromosome, this structure-altered X chromosome is obviously non-functional.
The presence of a structurally abnormal X chromosome could be explained both by an error in the formation of the sex cells that gave away the diseased organism, and by an error in the cell division of the fertilized egg.
Very rarely found, the fourth and last possible chromosomal set is the one characterized by cells with only one X chromosome and cells with only one X chromosome and portion of the Y chromosome (many times, this Y chromosome is attached to an autosomal chromosome).
Subjects with this chromosomal set are considered women, as the portion of the Y chromosome present is not sufficient to produce the male sexual characteristics.
Turner syndrome: is it hereditary?
Turner syndrome is not an inherited genetic disorder; after all, this could only be the case, considering that sick women who are carriers of the chromosomal alteration and of the pathology are generally sterile.
Turner Syndrome: Risk Factors
The chromosomal alterations that cause Turner syndrome are the result of totally random and unpredictable events.
Based on current knowledge, family history does not appear to affect the onset of the disease in any way.
clinical.The age of the patient is an important factor; in fact, some manifestations of the disease are characteristic of the prenatal phase and of early childhood, others of adolescence and still others of adulthood.
Prenatal age and early childhood
Lymphedema
The most common symptom in prenatal age and in the first years of life is lymphedema.
Lymphedema consists of a stagnation of lymph in some parts of the body, both organs and tissues; this stagnation causes localized swelling.
In prenatal age, lymphedema affects the neck area; at this stage, it is also called cystic hygroma.
In childhood, lymphedema also extends to the hands and feet (ankles).
Congenital Cardiovascular Anomalies
Carriers of Turner syndrome may have congenital cardiovascular malformations; among these anomalies, the bicuspid aortic valve, aortic coarctation, aortic valve stenosis and aortic regurgitation stand out in particular.
Congenital Renal Anomalies
About one third of women with Turner syndrome are born with kidney abnormalities; specifically, it could:
- Introduce the so-called horseshoe kidney,
- Missing of a kidney (renal agenesis),
- Suffering from a poor blood supply to the kidneys.
In general, patients with renal abnormalities are more prone to hypertension and urinary tract infections.
Physical Anomalies
The appearance of women with Turner syndrome is characterized by a series of physical characteristics, which are evident already during the first years of life.
Among these possible physical connotations, the following deserve a mention:
- The short neck and the so-called pterigium colli;
- Ptosis and epicanthus;
- Low ears and prominent auricle;
- The broad chest and nipples greatly spaced from each other;
- The fish mouth and the high and hyper-convex palate (ogival palate);
- The nails tight and pointing upwards;
- The presence of numerous moles;
- The cubitus valgus (anomalous lateral deviation of the forearm starting from the elbow);
- The low hairline at the back of the head;
- The small mandible (micrognathia) and the backward displacement of the maxilla (retrognathia);
- The fingers, both of the hands and feet, are shorter than normal (in most cases, the fourth and fifth metacarpals, and the fourth and fifth metatarsal are involved);
- The flat foot.
In addition, the below average height and low growth rate should be noted.
Otitis Media
Girls with Turner syndrome tend to suffer from recurrent acute otitis media and effusive otitis media.
At a later age, this trend could have unpleasant consequences.
Adolescence and Adulthood
At the onset of adolescence, Turner syndrome manifests itself with the problems that best characterize it: short stature and immature, rudimentary ovaries.
Short
In Turner syndrome, short stature is a hallmark, as the patients are evidently shorter than their peers.
The average height of Turner syndrome carriers is around 140 centimeters.
The problem of short stature depends on numerous reasons, first of all hormonal factors (growth hormone).
Immature ovaries
Failure to ripen the ovaries leads to insufficient production of female sex hormones (estrogen and progesterone).
In a woman of pubertal age, the scarcity of sex hormones makes it impossible for the correct development of sexual characteristics (puberty) and the onset of menstruation to occur; moreover, in women considered to be of childbearing age, it is a reason for sterility.
Turner Syndrome and Intelligence
Women with Turner syndrome tend to have some difficulties in learning the so-called non-verbal skills (eg: visual-constructive difficulties, visual-spatial intelligence, mathematics, spatial working memory, fine motor skills), while they have different points of strength in so-called verbal skills.
Beyond the aforementioned difficulties, people with Turner syndrome possess a "normal intelligence, which allows them to lead a productive life, both at school and at work."
Turner Syndrome: Complications
Various complications are associated with Turner syndrome, including:
- Cardiovascular problems. Congenital heart and aortic anomalies can result in pulmonary hypertension and aortic dissection.
Potentially fatal, problems of this nature are more common in women with monosomy Turner syndrome. - Hypertension. It is a possible consequence of kidney abnormalities.
- Recurrent kidney infections. It is another possible consequence of renal malformations.
- Hashimoto's thyroiditis and subsequent hypothyroidism. Hashimoto's thyroiditis is an autoimmune disease, which depresses the activity of the thyroid and the hormone production of thyroid hormones (hypothyroidism).
- Poor eyesight. Visual disturbances typical of Turner syndrome are amblyopia (lazy eye), myopia and strabismus.
- Hearing loss. It is common in patients who have suffered from recurrent otitis media.
- Skeletal problems. In women with Turner syndrome, the low amount of estrogen favors the onset of osteoporosis; moreover, many patients tend to develop scoliosis or hyperkyphosis.
- Diabetes mellitus and obesity.
Also of note is the association between Turner syndrome and conditions such as celiac disease and gastroesophageal reflux disease.
Turner syndrome: when to worry?
In a female individual, the following are suspicious signs: short stature, lymphedema in prenatal age and at an early age, wide neck and failure to develop puberty with all that goes with it.
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The "physical examination and family history are useful and necessary investigations, however not sufficient to outline a definitive diagnosis; certainly, they are fundamental in formulating a" diagnostic hypothesis.
Turner Syndrome: the Genetic Test
For the evaluation of the chromosomal structure, the object of the genetic analysis is usually a blood sample of the presumed patient, appropriately taken.
The genetic test allows to establish the absence of an X chromosome or any structural alterations to one of the two X chromosomes.
Waiting times for the results of such a test are usually around 15-20 days.
Turner Syndrome: Prenatal Diagnosis
Turner syndrome can also be diagnosed in prenatal age (ie before birth).
For its identification, amniocentesis or villocentesis and laboratory analyzes following these diagnostic tests can be used; moreover, for some years, fetal DNA testing has also been in use.
It should be remembered that the use of amniocentesis or CVS occurs only if there is "the suspicion that the unborn child is a carrier of a" genetic anomaly such as Turner syndrome; this is because they are two tests associated with a non-negligible risk of abortion.
, the cardiologist, the geneticist, the orthopedist, the urologist, the otolaryngologist, the ophthalmologist, the gastroenterologist and the dentist.It is also worth noting the importance of a psychology expert, as women with Turner syndrome often suffer from their condition.
Turner Syndrome and Hormone Therapy
A key role in the therapeutic management of Turner syndrome is hormone therapy based on the administration of:
- Growth hormone (GH) e
- Female sex hormones (estrogen and progesterone).
Growth Hormone in Turner Syndrome
As can be understood, GH-based hormonal therapy serves to promote the statural growth of patients.
Typically, this therapy begins in early childhood and continues until the age of 15-16 (the age at which a woman usually stops growing).
For the entire duration of treatment, there is one injection of growth hormone per day.
The GH hormone currently used is a product synthesized in the laboratory thanks to biotechnology; in the past, however, it came from the pituitary gland of cadavers.
In addition to ensuring greater availability of GH hormone, this change has made it possible to cancel the infectious risk associated with the use of a product coming from a corpse potentially carrying some transmissible infection.
During the entire period of GH-based hormone therapy, it is very important to monitor the patient's blood glucose, as this treatment could promote hyperglycemia (and diabetes).
For GH administration to be effective, it is essential to start treatment promptly.
Did you know that ...
In women with Turner syndrome, a correct GH-based hormone therapy can guarantee an overall growth of 5-9 centimeters, obviously at the end of the administration (therefore at 15-16 years).
Sex Hormones in Turner Syndrome
In patients with Turner syndrome, hormone therapy based on estrogen and progesterone is aimed at promoting pubertal development and inducing and regulating the menstrual cycle.
The beginning of the administration of the aforesaid hormones must coincide with the beginning of female puberty, which is dated around 11 years; in reality, to be more precise, at 11 he began estrogen-based therapy and only some time after that based on progesterone.
Exogenous estrogen is essential for the development of secondary sexual characteristics (eg breast formation) and the maturity of the uterus; it should also be added that it is important in limiting juvenile osteoporosis, which is a possible complication of Turner syndrome.
On the other hand, exogenous progesterone is essential to induce and regulate the menstrual cycle.
As a rule, sex hormone therapy should continue at least until the age of menopause, ie around the age of 50.
Regarding the method of administration, this can be oral (tablet) or transcutaneous (patch or gel).
As far as the dosage is concerned, this varies according to various factors, first of all the age of the patient (in general they increase with age).
Turner Syndrome and Psychotherapy
Women with Turner syndrome tend to have low self-esteem and suffer from depression; the reasons are:
- The absence of a normal reproductive system;
- The absence of normal secondary sexual characteristics;
- Sterility;
- The inability to lead a normal sex life;
- Short stature and physical abnormalities.
Psychotherapy and the closeness of the family can help patients to live their condition with greater serenity and to believe in the possibility of a "satisfying existence.
Turner Syndrome and Fertility
Generally, Turner syndrome involves infertility; however, there are rare cases in which the patient is fertile and can become pregnant.
For a woman with Turner syndrome, pregnancy can be a danger, as this condition causes heart stress which in a person with heart abnormalities (such as those with Turner syndrome) can have unpleasant consequences.
Turner Syndrome and Monitoring
Given the dangerous complications that can arise from Turner syndrome, it is essential that patients undergo periodic clinical checks, so as to prevent or, at least, manage certain consequences promptly.
Going into more detail, here are the exams and tests that a woman with Turner syndrome should perform on a regular basis:
- At least once a year, blood tests to check:
- Thyroid function;
- Hepatic function;
- Cholesterol Levels;
- Glycemia.
- Once every 2-4 years, blood tests to evaluate:
- Gluten tolerance;
- Estrogen level.
- Once a year, an assessment of hearing and, more generally, of the state of health of the ear.
- Once a year, an eye exam.
- Several times a year, a cardiological visit, including ECG and echocardiography, to check:
- The size and caliber of the aorta;
- The blood flow along the various cardiac compartments (atria and ventricles);
- The state of health of the pulmonary arteries.
- Blood pressure is measured several times a year to promptly identify any increases.
- Once a year, an ultrasound examination of the kidneys to observe the state of health of the kidney-bladder tract.
- Once a year, an evaluation of skeletal health, to promptly identify problems such as scoliosis and osteoporosis.
- At least once a year, a blood glucose test and weight control to prevent diabetes mellitus and obesity.
- Once a year, a dental visit to monitor any abnormalities of the maxilla or mandible.
