Klinefelter syndrome

Content

Introduction

Klinefelter's syndrome, also known as XXY syndrome, is characterized by having an extra X sex chromosome in people of the male sex.

Chromosomes are "packets" of genes found in every cell in the body. Every living being has a fixed number of chromosomes relative to the species to which it belongs. Man has a set of 46 chromosomes (karyotype), organized into 22 pairs of so-called chromosomes homologues (because they have two pairs of the same genetic material) and 2 sex chromosomes (they are not homologous because many genes are present only on the X chromosome and absent on the Y chromosome).

The two types of sex chromosomes, called X and Y, determine the genetic sex of each individual.

A female person has 22 pairs of homologous chromosomes and two X chromosomes (46, XX) while a male individual has 22 pairs of homologous chromosomes and two sex chromosomes: one X and one Y (46, XY).

The X chromosome is not a "female" chromosome and is present in all people. It is the presence of the Y chromosome that denotes the male sex of an individual.

In Klinefelter syndrome, a baby is born with 47 chromosomes instead of 46 because he has an extra copy of the X chromosome (47, XXY).
Individuals with Klinefelter syndrome are genetically male, however, the presence of an extra X chromosome has clinical consequences.

Klinefelter's syndrome is quite common in the general population, affecting approximately 1 in 1000 male infants. About 10% of people with karyotype 47, XXY have a situation called a mosaic, in which the various tissues of the human body have cell lines with different XY / XXY chromosomal makeup.

The chromosomal sets 48, XXXY and 49, XXXXY are quite rare and are associated with more serious disorders.

Health problems in males with Klinefelter's syndrome

Individuals with chromosomal makeup 47, XXY may not develop a true syndrome and lead a normal and healthy life.

Infertility, however, tends to be the main problem, although effective treatments are now available, especially if the chromosomal abnormality is ascertained (diagnosed) in childhood.

People with Klinefelter's syndrome have an increased risk of other chronic diseases, including:

  • type 2 diabetes
  • osteoporosis (brittle bones)
  • cardiovascular diseases
  • autoimmune diseases such as, for example, systemic lupus erythematosus
  • hypothyroidism (decreased thyroid function)
  • anxiety, depression and learning difficulties
  • male breast cancer, although very rare

Although these diseases are sensitive to specific treatments, testosterone replacement therapy can help reduce the risk of some of them.

More information and support

In Italy, with the decree of the President of the Council of Ministers (DPCM) of 12 January 2017 "Definition and updating of the essential levels of assistance, referred to in Article 1, paragraph 7, of Legislative Decree 30 December 1992, n. 502. (17A02015) ”(GU General Series n.65 of 18-03-2017 - Ordinary Supplement n. 15) the syndrome was included in the" list of chronic diseases (Annex 8) with code 066; on the other hand, other less frequent conditions with extranumerary X chromosome (48, XXXY and 49, XXXXY, etc) with exemption code RNG080 (chromosomal aneuploidy syndromes) were included in the new list of rare diseases (Annex 7).

For information on Klinefelter's syndrome, to get to know the clinical diagnosis and treatment centers of the National Rare Diseases Network and patient associations, it is possible to contact the Rare Disease Toll-Free Telephone (TVMR) 800.89.69.49. The number is active from Monday to Friday from 9.00 to 13.00.

Symptoms

Klinefelter's syndrome can cause symptoms (symptoms) that are so inconspicuous that they do not take the affected person to the specialist doctor.

The assessment of the condition (diagnosis) is often carried out on the occasion of analyzes performed for other problems such as, for example, couple infertility.

Some disorders (symptoms) and characteristic signs, although not always present, are:

  • in infants and young children, decreased muscle tone resulting in a delay in the ability to sit, crawl, walk and talk; in being more vulnerable, silent and less receptive to stimuli
  • during childhood, shyness and low self-esteem, learning problems with difficulties in math, reading, writing, spelling and attention; mild dyslexia and / or dyspraxia; reduced muscle tone, difficulty socializing or expressing feelings
  • in adolescenceXXY people are often taller than their family members (with long arms and legs), have wide hips, poor muscle tone and slower than usual muscle growth; they lack, or lack, of beard and hair; have small penis and testicles; they may have more or less developed breasts (gynecomastia)
  • in adulthood, Klinefelter syndrome is one of the most frequent causes of primary hypogonadism and azoospermia / oligospermia infertility in young adults. Low sexual desire may be present

Klinfelter's syndrome is not usually associated with intellectual problems.

Causes

Klinefelter syndrome is caused by one more X chromosome (47, XXY) than the normal chromosome (46, XY).

The extra X chromosome results in extra copies of genes in the cell which, by interfering with the development of the testes, result in the production of less testosterone (male sex hormone) than normally present levels.

The genetic information contained in the extra X chromosome can affect every cell in the body, or just a few (mosaic Klinefelter syndrome, present in less than 10% of patients).

In more than half of the cases, the anomaly originates from an error in the division of the maternal egg (meiosis) which determines the presence of an extra X. At the time of fertilization, therefore, the fusion of a Y sperm with an XX egg cell will give birth to a fetus with an XXY chromosomal set.

Less frequently, it will be the sperm that contains the extra X chromosome, so an XY sperm fertilizing an X egg cell will give birth to an XXY fetus with Klinefelter syndrome. This process, both in the egg cell and in the sperm, appears to happen randomly.

If you already have a child with Klinefelter syndrome, the likelihood of having another with the same condition is very low. It seems that there may be a relationship with the mother's age during pregnancy: the risk of having a child with Klinefelter's syndrome is slightly higher if the mother is 35 or older.

Diagnosis

XXY syndrome can be ascertained (diagnosed) in the pre-natal period through investigations such as amniocentesis and chorionic villus examination, carried out to discover diseases before birth.

The syndrome often goes unnoticed until adolescence or adulthood. In children, an alarm bell is represented by the smaller than normal size of the testicles and penis; in adolescents, by the delay in the appearance of secondary sexual characteristics (hair, beard, etc.).

In many cases, Klinefelter's syndrome is only discovered when a fertility test is performed.

In the presence of disturbances (symptoms) or suspicious physical manifestations, it is advisable to consult a specialist as soon as possible to undergo a karyotype examination for the search for the extra X chromosome and immediately begin appropriate hormonal therapies.

Therapy

There is no specific cure (therapy) for Klinefelter's syndrome, but a set of therapies to improve the ailments:

  • testosterone replacement therapy (TRT)
  • speech therapy during infancy to promote language development
  • educational support and behavioral in school to reduce learning difficulties or behavior problems
  • occupational therapy (rehabilitation to maintain and develop daily life skills) to address movement coordination problems associated with dyspraxia
  • Physiotherapy to promote the development of muscle tone and increase physical strength
  • psychological support for any mental health problems
  • infertility treatment, it may include assisted fertilization programs with the intra-cytoplasmic sperm injection technique (ICSI) which consists in the fertilization, in the laboratory, of an egg cell with sperm
  • breast reduction surgery to remove excess breast tissue
  • preservation of spermatozoa and immature germ cells taken from the testicle can give patients a chance to conceive over time

Testosterone Replacement Therapy (TRT)

TRT consists of taking drugs containing testosterone. It can be taken in gel or tablet form, in adolescents, or given as a gel or injections, in adults.

TRT can be prescribed by an endocrinologist and can promote the development of secondary sexual characteristics such as, for example, maturation of the voice, growth of beard and body hair, increase in muscle mass and tone, reduction of body fat.

During adulthood, TRT, when used long-term, can be useful in relieving many ailments associated with Klinefelter's syndrome such as osteoporosis, low mood, reduced sexual desire and low self-esteem. It is not effective on fertility.

Bibliography

Zitzmann M, Rohayem J. Gonadal dysfunction and beyond: Clinical challenges in children, adolescents, and adults with 47, XXY Klinefelter syndrome. American Journal of Medical Genetics. Part C: Seminars in Medical Genetics. First published 16 May 2020: 1-11

Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. Journal of Endocrinological Investigation. 2017; 40:123

Mayo clinic. Klinefelter syndrome (English)

NHS. Klinefelter syndrome (English)

In-depth link

Italian Union of Klinefelter Syndrome

Klinefelter is born

Italian Sicily Klinefelter Syndrome Association (ASKIS) - Onlus

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