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{{Turner syndrome}} | {{Turner syndrome}} | ||
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==Overview== | |||
Humans have 46 [[chromosomes]]. [[Chromosomes]] contain all of your [[genes]] and [[DNA]], the building blocks of the body. Two of these [[chromosomes]], the [[sex chromosomes]], determine if you become a [[boy]] or a [[girl]]. Females normally have two of the same [[sex chromosomes]], written as XX. Males have an X and a [[Y chromosome]] (written as XY). | |||
In [[Turner syndrome]], [[cells]] are missing all or part of an [[X chromosome]]. The condition only occurs in females. Most commonly, the female patient has only one X [[chromosome]]. Others may have two X [[chromosomes]], but one of them is incomplete. Sometimes, a female has some [[cells]] with two X [[chromosomes]], but other [[cells]] have only one. | |||
==Causes== | |||
[[Turner syndrome]] results from the following mechanisms. | |||
===Karyotypes=== | |||
'''Nondisjunction''' | |||
*During [[meiosis]] in either parent, a [[nondisjunction]] event can occur that leaves the [[gamete]], either [[oocyte]] or [[spermatocyte]], with neither X nor Y [[chromosome]]. | |||
*When this [[gamete]] combines with a gamete from the other parent (with a normal X [[chromosome]]), the [[embryo]] lacks the normal two chromosomes. | |||
*This leaves the [[embryo]] with 45 [[chromosomes]] and a single X chromosome, denoted 45,X (or, sometimes 45,XO, where the "O" is used as a placeholder). This is found in 50% of individuals with [[Turner syndrome]]. | |||
'''Chromosomal structure''' | |||
*An X [[chromosome]] can form a [[ring chromosome]] for example by losing a portion of the smaller arm, enabling the end of the long arm to wrap around. This is detrimental for the X chromosome in two ways. **Either the lost portion itself makes the chromosome less functional. | |||
**Or it causes [[nondisjunction]], as described above. Thus, the causes listed here are partly overlapping. | |||
*When such a [[ring chromosome]] combines with another ring chromosome in [[fertilization]], the pair is denoted as 46, XrXp-, where rXp- means a ring chromosome missing the small (p) arm of the [[chromosome]]. | |||
*Another variant of [[abnormal chromosomal structure]] is chromosomes with two long arms of the X [[chromosomes]] attached, and are called [[isochromosomes]]. | |||
*Variants of chromosomal structure occur in 30% of individuals with [[Turner syndrome]]. | |||
'''Nonfunctional Y''' | |||
*Very rarely, the [[embryo]] has a normal X [[chromosome]] and a portion of the Y chromosome. | |||
* In these cases, the Y chromosome does not have a functional SRY (and so develops as a female), the diagnosis is XY [[gonadal dysgenesis]].[1] | |||
*It is possible that some [[Turner syndrome]] diagnosis is due to [[gonadal dysgenesis]], particularly when it is caused by a large deletion of the Y chromosome. | |||
'''Mosaicism''' | |||
*Each of the causes mentioned above can occur as a [[mosaicism]], that is, some of the cells carry the [[mutation]] and some don't. That is, two cell lines of different [[genetic]] make ups exist. | |||
*This happens if the error takes place in one [[cell]] after the very first divisions of the early [[embryo]] after [[fertilization]]. | |||
*The exact mixture of the two different cell types depends on when the [[nondisjunction]] occurred. *However, if the nondisjunction occurs after enough divisions, the fraction of abnormal cells is probably not large enough to show any significant effects. | |||
*For instance, such a 45,X/46,XY individual will develop as a male, without [[Turner syndrome]]. | |||
**It is hypothesized that lower the percentage of [[mosaicism]], the lesser is the [[phenotype]] expression. | |||
*[[Mosaicism]] is found in about 20% of individuals with [[Turner syndrome]]. | |||
'''No single Y''' | |||
*There is no equivalent [[syndrome]] which results in a Y chromosome with no X, as such a condition is fatal in [[utero]]. | |||
'''Lyonization''' | |||
*In a normal 46 XX female, a process called [[lyonization]] inactivates one of the X [[chromosomes]] to equalize the number of expressible [[genes]] in males and females. | |||
*Some genes escape this inactivation and contribute to the pathophysiology in [[Turner Syndrome]]. | |||
*[[Turner syndrome]] might be due to the partial or complete absence of these inactivated [[genes]] and the presence of functional homologues of the Y chromosome. <ref name="pmid17562588">{{cite journal| author=Kesler SR| title=Turner syndrome. | journal=Child Adolesc Psychiatr Clin N Am | year= 2007 | volume= 16 | issue= 3 | pages= 709-22 | pmid=17562588 | doi=10.1016/j.chc.2007.02.004 | pmc=2023872 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17562588 }} </ref> | |||
'''Imprinting''' | |||
*[[Imprinting]] is an alteration in the expression of a [[gene]], depending on whether it has been inherited from the mother or father. | |||
*In the case of [[imprinting]], it is not known whether there is a specific correlation between retention of the maternal or paternal [[chromosome]] and expression of particular [[phenotype]]. | |||
*[[Short Stature]] is said to be due to the [[haploinsufficiency]] of the [[short stature homeobox (SHOX gene)]] which is located on the [[pseudoautosomal]] region of the X chromosome. | |||
**The [[SHOX gene]] is also responsible for [[skeletal]] abnormalities such as [[high arched palate]], abnormal [[auricular]] development, [[cubitus valgus]], [[genu valgum]], [[Madelung deformity]] and [[short metacarpals]]. | |||
==References== | ==References== | ||
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Latest revision as of 10:47, 9 September 2020
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Turner syndrome Microchapters |
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Risk calculators and risk factors for Turner syndrome causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]
Overview
Humans have 46 chromosomes. Chromosomes contain all of your genes and DNA, the building blocks of the body. Two of these chromosomes, the sex chromosomes, determine if you become a boy or a girl. Females normally have two of the same sex chromosomes, written as XX. Males have an X and a Y chromosome (written as XY).
In Turner syndrome, cells are missing all or part of an X chromosome. The condition only occurs in females. Most commonly, the female patient has only one X chromosome. Others may have two X chromosomes, but one of them is incomplete. Sometimes, a female has some cells with two X chromosomes, but other cells have only one.
Causes
Turner syndrome results from the following mechanisms.
Karyotypes
Nondisjunction
- During meiosis in either parent, a nondisjunction event can occur that leaves the gamete, either oocyte or spermatocyte, with neither X nor Y chromosome.
- When this gamete combines with a gamete from the other parent (with a normal X chromosome), the embryo lacks the normal two chromosomes.
- This leaves the embryo with 45 chromosomes and a single X chromosome, denoted 45,X (or, sometimes 45,XO, where the "O" is used as a placeholder). This is found in 50% of individuals with Turner syndrome.
Chromosomal structure
- An X chromosome can form a ring chromosome for example by losing a portion of the smaller arm, enabling the end of the long arm to wrap around. This is detrimental for the X chromosome in two ways. **Either the lost portion itself makes the chromosome less functional.
- Or it causes nondisjunction, as described above. Thus, the causes listed here are partly overlapping.
- When such a ring chromosome combines with another ring chromosome in fertilization, the pair is denoted as 46, XrXp-, where rXp- means a ring chromosome missing the small (p) arm of the chromosome.
- Another variant of abnormal chromosomal structure is chromosomes with two long arms of the X chromosomes attached, and are called isochromosomes.
- Variants of chromosomal structure occur in 30% of individuals with Turner syndrome.
Nonfunctional Y
- Very rarely, the embryo has a normal X chromosome and a portion of the Y chromosome.
- In these cases, the Y chromosome does not have a functional SRY (and so develops as a female), the diagnosis is XY gonadal dysgenesis.[1]
- It is possible that some Turner syndrome diagnosis is due to gonadal dysgenesis, particularly when it is caused by a large deletion of the Y chromosome.
Mosaicism
- Each of the causes mentioned above can occur as a mosaicism, that is, some of the cells carry the mutation and some don't. That is, two cell lines of different genetic make ups exist.
- This happens if the error takes place in one cell after the very first divisions of the early embryo after fertilization.
- The exact mixture of the two different cell types depends on when the nondisjunction occurred. *However, if the nondisjunction occurs after enough divisions, the fraction of abnormal cells is probably not large enough to show any significant effects.
- For instance, such a 45,X/46,XY individual will develop as a male, without Turner syndrome.
- Mosaicism is found in about 20% of individuals with Turner syndrome.
No single Y
- There is no equivalent syndrome which results in a Y chromosome with no X, as such a condition is fatal in utero.
Lyonization
- In a normal 46 XX female, a process called lyonization inactivates one of the X chromosomes to equalize the number of expressible genes in males and females.
- Some genes escape this inactivation and contribute to the pathophysiology in Turner Syndrome.
- Turner syndrome might be due to the partial or complete absence of these inactivated genes and the presence of functional homologues of the Y chromosome. [1]
Imprinting
- Imprinting is an alteration in the expression of a gene, depending on whether it has been inherited from the mother or father.
- In the case of imprinting, it is not known whether there is a specific correlation between retention of the maternal or paternal chromosome and expression of particular phenotype.
- Short Stature is said to be due to the haploinsufficiency of the short stature homeobox (SHOX gene) which is located on the pseudoautosomal region of the X chromosome.
- The SHOX gene is also responsible for skeletal abnormalities such as high arched palate, abnormal auricular development, cubitus valgus, genu valgum, Madelung deformity and short metacarpals.
References
- ↑ Kesler SR (2007). "Turner syndrome". Child Adolesc Psychiatr Clin N Am. 16 (3): 709–22. doi:10.1016/j.chc.2007.02.004. PMC 2023872. PMID 17562588.