Turner syndrome: what are the symptoms?

It is a rare genetic disorder caused by an abnormality in the X chromosome pair.

Turner syndrome is a rare genetic disorder that affects only women, linked to the total or partial absence of the X chromosome.

The name is due to Henry Turner, who in 1938 first observed its characteristics, while only years later, in 1964, the origin of the pathology was identified.

The disease affects one in 2,500 healthy births, but it is estimated that 99 percent of fetuses affected by this abnormality do not survive and do not arrive at birth. Turner’s syndrome belongs to the category of rare diseases, defined as such if they affect (according to the threshold set by the European Union) no more than five cases per 10,000 people.

Causes of the disease

Turner syndrome is due to a chromosomal abnormality: people who are affected usually have only one X chromosome, a condition called monosomy. In other cases, both X chromosomes are present, but one of them has structural alterations.

Since the sex chromosomes indicate the sex of a person and the characteristics that follow from it, women with this syndrome present abnormalities first of all at the level of the reproductive system, as well as distinctive somatic characteristics and a predisposition to the development of other diseases including diabetes, celiac disease, osteoporosis.

The total or partial absence of the X chromosome is probably due to an error during the process of mitosis, or division, of the fertilized egg. The time when this division error occurs determines the genotype of women with Turner syndrome:

• if the error occurs at an early stage, all cells have 45 chromosomes and only one X chromosome. In this case we speak of monosomy X, which affects about 60 percent of cases.
• if the error occurs at a later stage, i.e. when the fertilized egg has already begun its own cell division, only one part of the cells of the body will contain only one X chromosome, while the remaining part will have two. This particular condition is called genetic mosaicism.

In other cases, structural alterations of the X chromosome may be present, such as:

• deletion of certain sections of the chromosome
• the so-called “ring” chromosome, which occurs when the chromosome closes on itself losing, at the point of joining the two extremes, genetic material.
• the isochromosome, which occurs when the X chromosome is formed by two identical arms (long or short).

And finally the case in which the Y chromosome is present in the karyotype, in whole or only in small parts that can be free or attached to other chromosomes, following a translocation process.

Clinical picture

The clinical picture of people with Turner syndrome can be very heterogeneous, in relation to the lack of a variable number of genes present in the X chromosome, therefore it is not possible to define it unambiguously.

Manifestations may include both typical of Turner syndrome and situations in which physical abnormalities are blurred, if not absent. It seems that it is in particular the loss of the short arm of the X chromosome to play a role in determining the phenotype of the syndrome.

Although some physical characteristics may suggest the presence of the disease, the certain diagnosis occurs only through the determination of the chromosomal map, or karyotype. In addition to a blood sample in girls, the test can be carried out on a sample of amniotic fluid during amniocentesis.

If it does not happen during pregnancy, in some cases it can be diagnosed only around the age of ten and more rarely in adulthood, when it is difficult to correct the growth defect.

Symptoms of Turner syndrome

The symptoms and signs of Turner syndrome include:

• the face
• Skeleton
• the cardiovascular and urinary system
• the pace of growth
• pubertal development and the reproductive system.

The symptoms also differ depending on the age at which they appear: early childhood, adolescence or adulthood.

However, all people affected by the disease have sexual immaturity with amenorrhea, poorly defined sexual characteristics and genital apparatus that maintains the appearance of childhood.

A distinctive feature of Turner’s syndrome is short stature: girls with this disease are from the early years much shorter than their peers. Around three years of life, the first slowdown in growth occurs, with a positioning below the 3rd centile. This gap remains stable until puberty, when, due to the lack of estrogen production due to ovarian failure, neither normal pubertal development occurs with the appearance of menstruation nor an increase in stature, which in most girls remains less than 150 centimeters.

In the first years of life one of the typical manifestations is lymphedema, which manifests itself with swelling of hands and feet due to stagnation of liquids. When lymphedema affects the neck, it is called cystic hygroma.

Facial marks

Turner’s syndrome involves various manifestations of the head and face. Anomalies of the shape of the ears are very frequent, often associated with malformation of the Eustachian tubes, which facilitate the stagnation of mucus and therefore the onset of otitis, whose incidence is much higher than that of the healthy pediatric population. Recurrent infections can affect hearing ability, with possible repercussions on verbal learning.

Often the girls affected by the disease have a high and arched palate, a small jaw and a “fish” mouth. The neck is short and has typical folds due to the laxity of the tissues, a situation called pterygium. Drooping of the eyelids, up to cover a third of the diameter of the pupil, and low hairline on the nape of the neck are other typical signs of the disease.

Marks on the skeleton

With regard to skeletal abnormalities, congenital hip dysplasia is more frequent in newborns and scoliosis, which affects 10% of cases, in adolescents.

Girls affected by Turner syndrome also have a thoracic conformation that takes the name of “shield chest”, so-called because it is wide, with a flat and protruding sternum and with a distance between the nipples higher than normal.

Another typical sign is the so-called cubit valgus, a deformity of the elbow characterized by the fact that the axis of the arm forms with that of the forearm an angle open to the outside greater than 15 °. There may also be shortening of the fourth metacarpal and metatarsal bone, and poor development of the nails, which also appear convex.

Other events

Manifestations of the cardiovascular system may be found, with arterial hypertension and heart defects, including malformations of the aortic valve, such as the bicuspid aorta.

Aortic coarctation is also possible, which consists of a localized narrowing (stenosis) of the vein resulting in hypertension of the upper extremities, left ventricular hypertrophy and decreased blood supply to the abdominal organs and lower extremities.

The symptoms of aortic coarctation vary according to its severity and include headache, chest pain, feeling cold in the extremities and exhaustion, up to fulminant heart failure. This condition is treated surgically by removing the part affected by the narrowing or by means of an angioplasty and the installation of a stent.

The development of the ovaries occurs regularly until the fourth month of gestation; Later the process undergoes an involution and the tissue of the gonads is replaced by connective tissue.

Puberty and pubertal development occur spontaneously in less than half of the cases and only rarely, in 5-10 percent of cases, the residual ovarian function is sufficient to determine a spontaneous menarche.

Although very rare cases of natural pregnancies have been recorded, Turner syndrome must be considered as a condition of permanent infertility. However, the chances of pregnancy have now increased thanks to oocyte cryopreservation and assisted reproduction techniques.

Other consequences of the disease

As far as the urinary system is concerned,malformations of the kidneys are possible, with the so-called “horseshoe” shape.

People with Turner syndrome are also at greater risk of developing other diseases such as celiac disease, diabetes, thyroid dysfunction and osteoporosis. The latter is caused by prolonged estrogen deficiency. In some cases it is possible to find strabismus and visual defects, such as myopia.

Intellectual disability and mental retardation are not part of the clinical picture determined by Turner syndrome. However, some girls have learning disabilities, attention deficit and hyperactivity even if from the point of view of language they do not show below-average performance.

Treatments and therapies

For this disease there are no cures, but only supportive therapies aimed at counteracting some manifestations and improving, if possible, the quality of life.

Generally, girls, by the age of 13, undergo courses of treatment based on growth hormone GH and sex hormones, to induce pubertal development. With the administration of progesterone, the menstrual cycle is also induced.

In general, women with Turner syndrome, due to the risk of complications to which they are exposed, should undergo regular medical check-ups throughout their lives, in particular to monitor cardiovascular health and liver, kidney and thyroid function.