Mixed Gonadal Dysgenesis
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45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis, is a mutation of sex development in humans associated with
sex chromosome Sex chromosomes (also referred to as allosomes, heterotypical chromosome, gonosomes, heterochromosomes, or idiochromosomes) are chromosomes that carry the genes that determine the sex of an individual. The human sex chromosomes are a typical pair ...
aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell (biology), cell, for example a human somatic (biology), somatic cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more plo ...
and mosaicism of the
Y chromosome The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...
. It is a fairly rare chromosomal disorder at birth, with an estimated incidence rate of about 1 in 15,000 live births. Mosaic loss of the Y chromosome in previously non-mosaic men grows increasingly common with age. The clinical manifestations are highly variable, ranging from partial virilisation and ambiguous
genitalia A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...
at birth, to patients with completely male or female
gonads A gonad, sex gland, or reproductive gland is a mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, ...
. Most individuals with this
karyotype A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...
have apparently normal male genitalia, and a minority have female genitalia, with a significant number of individuals showing genital abnormalities or mixed sex characteristics. A significantly higher than average number of other developmental abnormalities are also found in individuals with X0/XY mosaicism. Psychomotor development is normal.


Signs and symptoms

Conditions can be distinguished histologically and by
karyotyping A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...
. The observable characteristics (
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
) of this condition are highly variable, ranging from gonadal dysgenesis in males, to Turner-like females and phenotypically normal males. The phenotypical expression may be ambiguous, male or female, regardless of the extent of the mosaicism. The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity. There is a range of chromosomal anomalies within 45,X/46,XY where the variations are very complex, and the actual result in living individuals is often not a simple picture. Most patients with this karyotype are known to have abnormal gonadal
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
and heights considerably below their genetic potential. High gonadotropin levels have been described in both male and female patients, as well as low levels of
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
in male patients. Dosage loss of
SHOX gene The short-stature homeobox gene (SHOX), also known as short-stature-homeobox-containing gene, is a gene located on both the X chromosome, X and Y chromosomes, which is associated with short stature in humans if mutated or present in only one copy ...
is commonly associated with short stature.45,X/46,XY mixed gonadal dysgenesis
. ''Orfa.net''; August 2015.
Psychomotor development is normal. As the gonads may not be symmetrical, the development of the
Müllerian duct The paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo in the reproductive system of humans and other mammals that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive uroge ...
and
Wolffian duct The mesonephric duct, also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct, is a paired organ that develops in the early stages of embryonic development in humans and other mammals. It is an important structure that p ...
may be asymmetrical, too. Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma.


Causes

In a normal situation, all the cells in an individual will have 46 chromosomes, with one being an X and one a Y or with two Xs. However, sometimes during the early copying processes of
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...
and
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, one chromosome can be lost. In 45,X/46,XY, most or all of the Y chromosome is lost in one of the newly created cells. All the cells then made from this cell will lack the Y chromosome. All the cells created from the cells that have not lost the Y chromosome will be XY.45,X/46,XY Mosaicism: Report of 27 Cases
. ''Pediatrics'' Vol. 104 No. 2 August 1, 1999. pp. 304 -308
The 46,XY cells will continue to multiply at the same time as the 45,X cells multiply. The embryo, then the fetus, and then eventually the baby will have what is known as a 45,X/46,XY constitution. There are many chromosomal variations that cause the 45,X/46,XY karyotype, including malformation (isodicentricism) of the Y chromosomes, deletions of Y chromosome or translocations of Y chromosome segments. Such rearrangements of the Y chromosome can lead to partial expression of the SRY gene which may lead to abnormal genitals and testosterone levels. ''original research?''">Wikipedia:No original research">''original research?''/sup>


Diagnosis

Identification of 45,X/46,XY
karyotype A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...
has significant clinical implications due to known effects on growth, hormonal balance, gonadal development and histology. 45,X/46,XY is diagnosed by examining the chromosomes in a blood sample. The age of diagnosis varies depending on manifestations of disease prompting reason for
cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...
testing. Many patients are diagnosed prenatally due to fetal factors (increased nuchal fold, or abnormal levels of serum), maternal age or abnormal ultrasounds, while others will be diagnosed postnatal due to external genital malformation. It is not uncommon for patients to be diagnosed later in life due to short stature or delayed puberty, or a combination of both. 45,X/46,XY mosaicism can be detected prenatally through
amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ...
however, it was determined that the proportion of 45,X cells in the
amniotic fluid The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
cannot predict any phenotypic outcomes, often making prenatal genetic counselling difficult.


Management


See also

* Sex chromosome anomalies * Gonadal dysgenesis *
Mosaic (genetics) Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism i ...
*
Turner syndrome Turner syndrome (TS), commonly known as 45,X, or 45,X0,Also written as 45,XO. is a chromosomal disorder in which cells of females have only one X chromosome instead of two, or are partially missing an X chromosome (sex chromosome monosomy) lea ...


References


External links

{{DEFAULTSORT:45,X 46,XY mosaicism Sex chromosome aneuploidies Intersex variations