Materiały źródłowe

• #1 Klinefelter Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/945649-overview

  In 1942, Klinefelter et al published a report describing nine men with a constellation of features: testicular dysgenesis, microorchidism, eunuchoidism, gynecomastia, elevated urinary gonadotropins, and azoospermia. The etiology was thought to be due to an endocrine disorder of unknown cause, until 1959, when Jacobs et al recognized that Klinefelter syndrome was a chromosomal disorder in which there is an extra X chromosome, resulting in the karyotype 47,XXY. […] Today, the term Klinefelter syndrome (KS) refers to a group of chromosomal disorders in which the normal male karyotype, 46,XY, has at least one extra X chromosome. […] XXY aneuploidy, the most common human sex chromosome disorder, has a prevalence of 1 in 500 males. […] The addition of more than one extra X or Y chromosome to a normal male karyotype results in variable cognitive and physical abnormalities.

• #2 The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes

  https://www.mdpi.com/2073-4425/14/3/647

  Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500/1000 per male live birth (karyotype 47,XXY). […] The extra X chromosome originates from nondisjunction errors of the sex chromosomes, being 50% of paternal origin and 50% of maternal origin. Paternal nondisjunction of sex chromosomes occurs during meiosis I, whereas maternal nondisjunction can occur during meiosis I or II, or during early post-zygotic mitotic divisions. […] Several mechanisms, including non-inactivation of specific genes, overexpression of somatic genes, altered methylation status, and altered androgen receptor sensitivity, have been proposed to explain the variability (severity) of the KS phenotype. […] The presence of an extra X chromosome, androgen deficiency, and mosaicism are thought to influence the KS phenotype.

• #3 Klinefelter Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482314/

  Klinefelter syndrome is a genetic condition characterized by the presence of 2 or more X chromosomes in a phenotypic male. […] The underlying genetic etiology supernumerary X chromosomes was identified in 1959. […] The most common karyotype in Klinefelter syndrome is 47,XXY, accounting for 90%. […] Klinefelter syndrome typically arises from a de novo nondisjunction event rather than being inherited, though inherited cases have been reported. […] The acquisition of the extra X chromosome is random, typically resulting from meiotic nondisjunction or postzygotic nondisjunction. […] The severity of the phenotype correlates with the amount of additional X chromosome material present.

• #4 Klinefelter Syndrome Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/945649-clinical

  In 1959, Klinefelter syndrome was found to be caused by a supernumerary X chromosome in a male. […] The 47,XXY karyotype of Klinefelter syndrome spontaneously arises when paired X chromosomes fail to separate (nondisjunction in stage I or II of meiosis, during oogenesis or spermatogenesis). […] Maternal and paternal meiotic nondisjunction each account for approximately 50% of Klinefelter syndrome cases. […] Seventy-five percent of maternal nondisjunction cases are caused by meiosis I errors, which are associated with increased maternal age. […] Increased paternal age has been linked to a possible increased risk of Klinefelter syndrome. […] Postfertilization nondisjunction is responsible for mosaicism, which is seen in approximately 10% of Klinefelter syndrome patients. […] The most common karyotype is 47,XXY, which accounts for 80-90% of all cases.

• #5 Klinefelter syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/klinefelter-syndrome/symptoms-causes/syc-20353949

  Klinefelter syndrome occurs because of a random change in the egg or the sperm that causes a baby assigned male at birth to be born with an extra X sex chromosome. The condition is not passed down in families. […] Klinefelter syndrome can be caused by: One extra copy of the X sex chromosome in each cell (XXY), the most common cause. […] An extra X sex chromosome in some of the cells. This is called mosaic Klinefelter syndrome and may result in fewer symptoms. […] More than one extra copy of the X sex chromosome, which is rare and results in a severe form of the syndrome. […] In people assigned male at birth, extra copies of genes on the X sex chromosome can interfere with sexual development and fertility.

• #6 Klinefelter syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klinefelter-syndrome/

  Klinefelter syndrome is a sex chromosome disorder that results from the presence of an extra X chromosome in cells. People typically have 46 chromosomes in each cell, two of which are the sex chromosomes. Females typically have two X chromosomes (46,XX), and males typically have one X and one Y chromosome (46,XY). Most often, people with Klinefelter syndrome have the usual X and Y chromosomes, and one extra X chromosome, for a total of 47 chromosomes (47,XXY). […] Individuals with Klinefelter syndrome have an extra copy of multiple genes on the X chromosome. The activity of these extra genes may disrupt many aspects of development and are responsible for the common signs and symptoms of Klinefelter syndrome. Researchers are working to determine which genes contribute to the specific developmental and physical differences that can occur in people with Klinefelter syndrome.

• #7 Klinefelter syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Klinefelter_syndrome

  Klinefelter syndrome is not an inherited condition. The extra X chromosome comes from the mother in approximately 50% of the cases. Maternal age is the only known risk factor. Women at 40 years have a four-times-higher risk of a child with Klinefelter syndrome than women aged 24 years. […] The extra chromosome is retained because of a nondisjunction event during paternal meiosis I, maternal meiosis I, or maternal meiosis II, also known as gametogenesis. The relevant nondisjunction in meiosis I occurs when homologous chromosomes, in this case the X and Y or two X sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome or an egg with two X chromosomes. Fertilizing a normal (X) egg with this sperm produces an XXY or Klinefelter offspring. Fertilizing a double X egg with a normal sperm also produces an XXY or Klinefelter offspring.

• #8 Klinefelter Syndrome: Symptoms, Genetics, and Treatment

  https://www.verywellhealth.com/klinefelter-syndrome-2328931

  Klinefelter syndrome is caused by a random genetic error that occurs during the formation of the egg or sperm, or after conception. […] Most commonly, Klinefelter syndrome occurs due to a process referred to as nondisjunction in the egg or the sperm during meiosis. […] Nondisjunction during meiosis in the egg or sperm is the most common cause of Klinefelter syndrome, but the condition may also occur due to errors in the division (replication) of the zygote following fertilization. […] Klinefelter syndrome appears to occur more frequently with both older maternal and paternal age (over the age of 35). […] It’s important to note again that while Klinefelter is a genetic syndrome, it is not usually „inherited” and therefore does not „run in families.” Instead, it is caused by a random accident during the formation of the egg or the sperm, or shortly after conception occurs.

• #9 Klinefelter Syndrome | GLOWM

  https://www.glowm.com/section-view/heading/Klinefelter%20Syndrome/item/360

  The most frequent chromosomal complement associated with Klinefelter syndrome is 47,XXY, which may result from a nondisjunction during (1) meiosis I or meiosis II of oogenesis, or (2) meiosis I of spermatogenesis. […] Using polymorphic DNA markers, several investigators have found that the extra X chromosome is of paternal origin in 50% to 60% of cases and of maternal origin in the remaining 40% to 50% of cases. […] Among the maternal cases, nondisjunction is due to an error in meiosis I division in 70% of cases, an error in meiosis II division in 20% of cases, and a postzygotic mitotic error in 10%. […] Increased maternal age has been demonstrated in approximately 75% of cases due to maternal meiosis I nondisjunction. […] In the paternally derived 47,XXY cases, the X-Y nondisjunction must always occur in the first meiotic division.

• #10 Klinefelter Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2005/1201/p2259.html

  Klinefelter syndrome is caused by an additional X chromosome in males (47,XXY). […] The additional sex chromosomes in men with Klinefelter syndrome results from non-disjunction during meiosis and may have a paternal (50 to 60 percent) or maternal (40 to 50 percent) origin. […] Although Klinefelter syndrome encompasses the specific clinical consequences observed in men with an XXY karyotype, there are variant karyotypes that can include additional X chromosomes (e.g., XXXY, XXXXY) or additional X and Y chromosomes (e.g., XXYY). […] Physical manifestations of Klinefelter syndrome are relatively moderate compared with autosomal trisomies (e.g., Down syndrome) because when additional X chromosomes are present, one is predominantly inactivated. […] Mosaicism occurs in 15 percent of men with an additional X chromosome and generally results in a milder phenotype.

• #11 Klinefelter Syndrome (XXY Syndrome) – Symptoms, & Causes

  https://www.invitra.com/en/klinefelter-syndrome/

  Klinefelter syndrome (KS), also known as XXY syndrome, is a genetic cause of male infertility. Children born with this genetic disease have an extra X chromosome, hence the name. Their karyotype is 47,XXY. […] The fact that an embryo grows with an extra X chromosome is due to an error at some point of the meiosis process during gametogenesis (egg and sperm formation) in the parents. […] To be precise, Klinefelter syndrome can be caused by nondisjunction of a pair of chromosomes: X chromosomes do not separate during prophase of meiosis I in females. […] Depending on whether nondisjunction is associated with the father or the mother, we can distinguish two different case scenarios: Errors during oogenesis The eggs produced contain two X chromosomes instead of a single one. Errors during spermatogenesis The sperms produced contain a X chromosome and a Y chromosome, instead of a single X or Y chromosome.

• #12 Klinefelter Syndrome Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/945649-clinical

  Mosaicism (46,XY/47,XXY) is observed in about 10% of cases. […] The mosaic forms of Klinefelter syndrome are due to mitotic nondisjunction after fertilization of the zygote. […] These forms can arise from a 46,XY zygote or a 47,XXY zygote. […] Variant forms of Klinefelter syndrome include 48,XXXY; 49,XXXXY; 48,XXYY; and 49,XXXYY.

• #13 Klinefelter syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Klinefelter_syndrome

  Another mechanism for retaining the extra chromosome is through a nondisjunction event during meiosis II in the egg. Nondisjunction occurs when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate. An XX egg is produced, which when fertilized with a Y sperm, yields an XXY offspring. This XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in approximately one in 500 live male births.

• #14 Klinefelter Syndrome: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21116-klinefelter-syndrome

  Klinefelter syndrome occurs when theres an extra X chromosome in your genetic code. This change happens before birth and can happen in a few different ways: […] A sperm cell carries an extra X chromosome. […] An egg cell holds an extra X chromosome. […] Cells divide incorrectly during early fetal development. Healthcare providers call this mosaic Klinefelter syndrome. (It occurs when some but not all of your cells have an extra X chromosome.)

• #15 About Klinefelter Syndrome

  https://www.genome.gov/Genetic-Disorders/Klinefelter-Syndrome

  Klinefelter syndrome is a condition that occurs in men as a result of an extra X chromosome. […] Most often, Klinefelter syndrome is the result of one extra X (written as XXY). […] The additional sex chromosome results from a random error during the formation of the egg or sperm. […] About half of the time the error occurs in the formation of sperm, while the remainder are due to errors in egg development. […] Women who have pregnancies after age 35 have a slightly increased chance of having a boy with this syndrome.

• #16 Hormones.gr

  http://www.hormones.gr/8592/article/klinefelter-syndrome-and-medical-treatment:-hypogonadism%E2%80%A6.html

  The only identified risk for conception of a Klinefelter fetus is increasing maternal age due to increased meiotic non-disjunction. […] The finding of an increased second to fourth finger ratio in KS gives indications that hypogonadism, so central to the syndrome, is already during fetal life affecting the fetus, giving rise to consequences measurable in adulthood. […] The full effect of the apparent hypogonadal intrauterine milieu present in KS is not as yet understood but could very well also be exerting a negative influence, especially on neurocognition and masculinization of the brain. […] Overall, it seems likely that the metabolic consequences of KS are, to a large extent, driven by the resulting hypogonadism, but also that another and so far unknown effect is in play. […] The background for the thrombosis proneness in Klinefelter syndrome is not thus far understood.

• #17 Klinefelter Syndrome: Causes, Symptoms, and Treatment Options • Yesil Health

  https://yesilhealth.com/your-health/klinefelter-syndrome-causes-symptoms-and-treatment-options/

  While there are no specific risk factors that can cause Klinefelter syndrome, research suggests that the following may increase the likelihood of having a child with the condition: Advanced maternal age: The risk of Klinefelter syndrome increases with the mothers age, particularly after 35 years. Paternal age: Similar to maternal age, the risk of Klinefelter syndrome may increase with the fathers age. Familial history: Having a family history of Klinefelter syndrome or other chromosomal abnormalities may increase the risk. […] Its essential to note that these risk factors do not guarantee the development of Klinefelter syndrome, and many cases occur without any identifiable risk factors.

• #18 Klinefelter syndrome – UF Health

  https://ufhealth.org/conditions-and-treatments/klinefelter-syndrome

  Klinefelter syndrome results when a male child is born with at least 1 extra X chromosome. They have 47 chromosomes instead of 46. This is written as 47, XXY. […] Klinefelter syndrome occurs as a random event. There is no exact cause, and the condition is not inherited. […] Klinefelter syndrome occurs in about 1 out of 500 to 1,000 male infants. Women who get pregnant after age 35 are slightly more likely to have a male child with this syndrome than younger women.

• #19 Klinefelter syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/klinefelter-syndrome/

  Some people with features of Klinefelter syndrome have an extra X chromosome in only some of their cells, while the other cells have one X and one Y chromosome. Rarely, some cells may have additional chromosome abnormalities. In these individuals, the condition is described as mosaic Klinefelter syndrome (46,XY/47,XXY). It is thought that approximately 10 percent of individuals with Klinefelter syndrome have the mosaic form. People with mosaic Klinefelter syndrome may have milder signs and symptoms than those with the extra X chromosome in all of their cells, depending on what proportion of cells have the additional chromosome. […] Some conditions that are caused by the presence of more than one extra sex chromosome in each cell are described as variants of Klinefelter syndrome. These conditions include 48,XXXY syndrome, 48,XXYY syndrome, and 49,XXXXY syndrome. Like Klinefelter syndrome, these conditions affect male sexual development and can be associated with learning disabilities and problems with speech and language development. However, the features of these disorders tend to be more severe than those of Klinefelter syndrome and affect more parts of the body. As doctors and researchers have learned more about the differences between these sex chromosome disorders, they have started to classify them as separate conditions.

• #20 Klinefelter Syndrome – The Oncofertility Consortium

  https://oncofertility.msu.edu/non-malignant-conditions/klinefelter-syndrome/

  Klinefelter syndrome is a chromosomal condition that affects male physical and cognitive development. The syndrome is the result of one additional X chromosome, or a 47,XXY karyotype. The extra X chromosome interferes with male sexual development, often preventing the testes from functioning normally and reducing the levels of testosterone. […] Klinefelter syndrome occurs due to a random event when the reproductive cells (eggs and sperm) are forming in the parent. The random event is called nondisjunction and the resulting reproductive cell has an abnormal number of chromosomes. Nondisjunction is often associated with increased maternal age. […] The mosaic forms of Klinefelter syndrome, like 46,XY/47,XXY are also not inherited. Mosaic Klinefelter syndrome results from a random event in cell division early in fetal development. As a result- there are two cell lines within the body. Individuals with mosaic Klinefelter may have less severe signs and symptoms.

• #21 Klinefelter Syndrome (for Teens) | Nemours KidsHealth

  https://kidshealth.org/en/teens/klinefelter.html

  Klinefelter syndrome isn’t passed down through families like some genetic diseases. Instead, it happens randomly from an error in cell division when a parent’s reproductive cells are being formed. If one of these cells is part of a successful pregnancy, a baby boy will have the XXY condition. […] The XXY condition can affect some or all of the body’s cells. If only some cells have the extra X chromosome, it’s called mosaic Klinefelter syndrome. Guys with this condition often have milder signs and symptoms. Some may not even know they have Klinefelter syndrome until later in life. Other boys have more than two X chromosomes. Their condition may be more severe.

• #22 Klinefelter Syndrome | GLOWM

  https://www.glowm.com/section-view/heading/Klinefelter%20Syndrome/item/360

  Mosaicism of the karyotype 46,XY/47,XXY, which accounts for approximately 15% of Klinefelter syndrome cases, probably arises by nondisjunction or anaphase lag in the zygote or embryo. […] The etiology of the 48,XXYY chromosomal complement (more than 60 cases recorded) may best be explained by either successive nondisjunction at both the first and second meiotic division during spermatogenesis and syngamy of the resulting 25,XYY spermatozoon with a 23,X ovum, or nondisjunction at the second meiotic division in both parents so that syngamy occurs between a 24,XX ovum and a 24,YY sperm. […] The etiology of 49,XXXXY (more than 100 cases documented) is best explained by successive nondisjunction at either meiosis I or II of oogenesis.

• #23 Klinefelter Syndrome: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/945649-overview

  As the number of supernumerary X chromosomes increases, somatic and cognitive development are more likely to be affected. […] Gonadal development is particularly susceptible to each additional X chromosome, resulting in seminiferous tubule dysgenesis and infertility, as well as hypoplastic and malformed genitalia, as seen in polysomy X males. […] A form of primary testicular failure occurs in males with Klinefelter Syndrome, with elevated gonadotropin levels due to lack of feedback inhibition by the pituitary gland. […] It is unclear if the morbidity associated with Klinefelter syndrome is a result of hypogonadism and hyperestrogenism or is due to abnormal function of X chromosomelinked genes. […] However, research also indicates that by interfering with blood flow, microvascular dysfunction in the testes of patients with Klinefelter syndrome reduces circulating levels of testosterone.

• #24 X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome | Cell Death & Disease

  https://www.nature.com/articles/s41419-024-06792-6

  Klinefelter syndrome (KS) is caused by a 47,XXY karyotype. […] The testicular histology of men with KS comprises Leydig cell hyperplasia, hyalinized ghost tubules, and tubules containing only Sertoli cells. […] Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis. […] We hypothesize that only Sertoli cells which lose the additional X-chromosome can mature properly and induce gametogenesis at puberty. […] Our finding that both XIST-positive and -negative Sertoli cells can be found in testis biopsies from men with KS is in line with recent scRNAseq data. […] We also show that in adult men with KS, germ cells were only found inside tubules containing Sertoli cells with a nuclear morphology resembling type A Sertoli cells, lacking XIST expression, and with only one X-chromosome. […] Based on our data, we propose a model which stipulates that the remarkable heterogeneous testicular phenotype seen in adult men with KS is due to micro-mosaicism for the X-chromosome aneuploidy in the Sertoli cells and germ cells.

• #25 What causes Klinefelter syndrome (KS)? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/klinefelter/conditioninfo/causes

  The extra chromosome results from a random error that occurs when a sperm or egg is formed. […] This error causes an extra X chromosome to be included each time the cell divides to form new cells. In very rare cases, more than one extra X chromosome or an extra Y chromosome is included.

• #26 Klinefelter Syndrome: Symptoms, Causes, Treatments, and More

  https://www.healthline.com/health/klinefelter-syndrome

  Klinefelter syndrome is a genetic disease that causes biological males to be born with an extra copy of the X chromosome in their cells. […] People with Klinefelter syndrome are born with an extra X, causing their cells to have XXY chromosomes. This happens randomly during conception. About half the time the extra chromosome starts in the mothers egg. The other half of the time it comes from the fathers sperm. […] Klinefelter syndrome is usually random and not caused by anything either parent did. […] Females who have pregnancies after age 35 are slightly more likely to give birth to a baby with Klinefelter syndrome.

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