Turner Syndrome: Types, Causes, Genetic Basis, Signs, Symptoms, Diagnosis and Treatment

Known by its acronym as ST, it is a genetic disorder caused by the partial or complete absence of an X chromosome.

This is called monosomy and is usually caused by chromosomal nondisjunction .

Chromosomes are strands of deoxyribonucleic acid (DNA) that exist in all cells of the human body. Chromosomes contain instructions that make up the behavior and physical characteristics of a human.

It is a very common abnormality among sex chromosome disorders, with an incidence of 1 in 2000 live females. About 1 in 2,500 girls is born with the condition, but it likely affects more pregnancies that do not survive to term.

In the United States, about 70,000 women are believed to have Turner syndrome. Life expectancy is slightly shorter than it would be for most people.

Its typical phenotype includes short stature, primary or secondary amenorrhea (the former is much more common), ovarian failure due to ovaries in the vein, webbed neck, heart defects, and often hypothyroidism .

Other characteristics of this condition that can vary among women who have Turner syndrome include: swelling (lymphedema) of the hands and feet, skeletal abnormalities, and kidney problems.

It is usually treated with growth hormone and estrogen replacement to allow normal height growth and the development of pubertal features.

Types

About half of the women living with Turner syndrome have only one X chromosome, and this is called Turner syndrome without pure mosaic, with a 45, X genotype. However, partial absence can also cause the same phenotype. .

It has now been established that 99% of pure non-mosaic Turner syndrome is lost through first trimester miscarriage.

This leads to the conclusion that most individuals who have Turner syndrome do in fact have a certain degree of mosaicism, which is compatible with life and allows them to survive.

This can be detected by technologies such as fluorescent in situ interphase hybridization (FISH) in a large number of cytogenetic samples when a non-mosaic Turner syndrome genotype is found in the karyotype.

What Causes Turner Syndrome?

Turner syndrome occurs when part or all of an X chromosome is missing from most or all of the cells in a girl’s body. A girl normally receives one X chromosome from each parent.

The error leading to the missing chromosome appears to occur during the formation of the egg or sperm.

Most commonly, a girl with Turner syndrome has only one X chromosome. Occasionally, she may have a partial second X chromosome. Because part or all of a chromosome is missing, certain genes are missing. Loss of these genes leads to symptoms of Turner syndrome.

Sometimes girls with Turner syndrome have some cells that are missing an X chromosome (45, X) and some that are normal. This is because not all cells in the body are exactly the same, so some cells may have the chromosome, while others may not.

This condition is called mosaicism (pronounced moh-ZEY-uh-siz-uhm). If the second sex chromosome is missing from most of a girl’s cells, then she likely has symptoms of Turner syndrome.

If the chromosome is missing only some of your cells, you may have no symptoms or only mild symptoms.

Abnormal cells may have only one X (monosomy) (45, X) or may be affected by one of several types of partial monosomy, such as a deletion of the short p arm of an X chromosome (46, X, del (Xp)) or the presence of an isochromosome with two arms q (46, X, i (Xq)).

Turner syndrome has distinct characteristics due to the lack of pseudoautosomal regions, which are normally spared from inactivation of X.

In mosaic individuals, cells with monosomy X (45, X) can occur together with cells that are normal (46, XX), cells that have partial monosomies, or cells that have a Y chromosome (46, XY).

The presence of mosaicism is estimated to be relatively common in affected individuals (67-90%).

Inheritance

In most cases where monosomy occurs, the X chromosome comes from the mother. This may be due to a nondisjunction in the father.

Meiotic errors leading to X production with abnormal Y chromosome po arm deletions are also found primarily in the father.

On the other hand, the X isochromosome or the X chromosomal ring are formed with the same frequency by both parents. In general, the functional X chromosome usually comes from the mother.

In most cases, Turner syndrome is a sporadic event, and for parents of a person with Turner syndrome, the risk of recurrence does not increase in subsequent pregnancies.

Rare exceptions may include the presence of a balanced X chromosome translocation in one parent, or when the mother has a 45.X mosaicism restricted to her germ cells.

Genetic bases of Turner syndrome

Turner syndrome with a partial absence of an X can be due to any of the following:

  • The long or short arm of the X chromosome is missing.
  • An X chromosome ring where both ends have been fused with the loss of some genetic material.
  • Isochromosome formation of the long arm of the X.
  • Turner syndrome in which cells contain 45, X and 46, XX variably, resulting in a milder phenotype due to partial expression of both X chromosomes.
  • Primary amenorrhea is more common with classic Turner syndrome (45, X), while menstruation can begin with other karyotypes, particularly mosaic forms. However, secondary amenorrhea soon sets in due to ovarian failure.

Lyonization

Genetic studies have already shown that in normal women with two X chromosomes, one X is always randomly inactivated during embryo development.

This phenomenon is called lyonization or dose compensation, and it is a mechanism to ensure that men and women have the same number of active X-linked genes.

On the other hand, it is also known that several genes on the Lyon X chromosome escape total inactivation and are necessary for the female phenotype.

Therefore, Turner syndrome is suspected to be due to the absence (in part or in full) of these genes, which must be present in double doses in normal women.

Gen SHOX

These genes include SHOX (short-statute homeobox) in the pseudo-autosomal region of the X chromosome, which may be responsible for growth retardation and skeletal defects, such as sunken ears, arched palate, damaged knees, and high angle loading. (abnormal outward angulation of the elbows).

Genetic footprint

Another phenomenon called genomic imprinting may be responsible for some features of Turner syndrome. The expression of an imprinted gene depends on which parent originated, be it maternal or paternal.

Some studies have shown that girls with Turner syndrome in whom the only X chromosome came from the mother had greater cognitive impairment, possibly due to abnormal development of the temporal and occipital lobes of the brain.

However, others have contradicted this, and this area needs more research.

Paternal meiotic error

TS is usually sporadic and its incidence is not related to maternal age. Of the 50% of individuals with Turner syndrome who have the 45, X genotype, three out of four have been found to have a single X, which is derived from the mother, as determined by several different methods.

In cases of partial retention of the second X chromosome, including ring chromosomes or marker chromosomes, the intact chromosome was usually of maternal origin.

This seems to rule out a meiotic error in the maternal ovum and suggest that it occurs during the generative process of the paternal sperm.

This type of error would cause a high rate of chromosome loss during mitosis due to delayed anaphase (if the genotype is 45, X) or due to nondisjunction (if mosaicism such as 47, XXX; 46, X, of the Xp is present; or 46, X, marker X).

Gametogenetic or postzygotic error

In contrast, with mosaic X Turner syndrome or Turner syndrome with an isochromosome, the chance of having maternal and paternal isochromosomes was approximately equal.

This means that either an error occurred during the formation of the gamete or after the formation of the zygote and in the first cell division after fertilization.

Partial deletions X

Partial X deletions can also cause ovarian failure, such as removal of Xp11 (related to ovarian failure by 50%) and removal of Xp21 (more likely to have secondary amenorrhea).

Therefore, the Xp deletion is likely the cause of a Turner syndrome phenotype, especially of short stature.

The presence of 46, X, i (Xq) pure line mosaic with two long arms Xq and no short arms (Xp) is also associated with some patients with Turner syndrome.

Gonadal failure is associated with the Xq deletion, and the more proximal the deletion, the more severe the expression.

Therefore, Xq26-q28 and Xq13.3-q21.1 are now referred to as POF1 and POF2 (for primary ovarian failure), respectively, due to mutations or rearrangements of chromosomal material that negatively affect ovarian gene expression.

Turner syndrome signs and symptoms

Girls with Turner syndrome are generally shorter than average girls their age. They may have a hard time entering or going through puberty due to ovarian failure .

Each girl with Turner Syndrome is unique and may have different characteristics. Some girls only have a few functions, while others may have more.

These are the different problems at each stage of life that a girl with Turner syndrome may face from infancy to adulthood:

Problems during childhood

Swollen hands and feet and difficulties in sucking and swallowing.

Problems during childhood

Hearing and vision

Middle ear infections are more common and hearing can be affected. The eyes should be tested for myopia, squint, and ptosis (drooping of the eyelid).

Growth

Short stature is the most common feature in Turner syndrome. The final height can be increased through the use of growth hormone.

Learning and development

Intelligence falls into the normal range. Some may have difficulties with spatial skills, resulting in difficulties with math and geometry.

Problems during adolescence

Sexual development

The ovaries may not function properly, and therefore some girls may not develop secondary sexual characteristics, such as growth of pubic hair and hair under the armpit, and breast development.

Some girls can start puberty on their own, but puberty can stop before girls are fully mature. Some girls may not experience any pubertal changes and will need hormone replacement therapy.

Infertility is a common problem in women with Turner syndrome due to non-functioning ovaries.

Problems in adulthood

Hormone replacement therapy is necessary for non-functioning ovaries, sterility, and risk of developing hypertension .

Heart problem: The aortic valve may be abnormal or the base of the aorta may widen with increasing age.

You may have osteoporosis (bone loss).

Diagnosis and treatment options for Turner syndrome

Although the diagnosis is made initially with physical signs, it must be confirmed with a blood test called a chromosomal karyotype.

For growing girls with short stature, growth hormone therapy can help them grow better and increase their final height.

Hormone replacement therapy is usually started around puberty to help them start puberty or go through pubertal changes. The replacement of female hormones with estrogens is also necessary to maintain bone strength and prevent osteoporosis.

Each individual child requires their own personal assessment and advice on the management and treatment of the condition. You should speak with a doctor familiar with the care of Turner syndrome regarding treating your child’s needs.