XX gonadal dysgenesis
Encyclopedia
This syndrome is inherited as an autosomal
disease. It affects both males and females but the phenotype differs. In both sexes sensorineural deafness occurs but in females ovarian dysgenesis also occurs.
XX gonadal dysgenesis is a type of female hypogonadism
in which no functional ovaries are present to induce puberty
in an otherwise normal girl whose karyotype
is found to be 46,XX. With nonfunctional streak ovaries she is low in estrogen levels (hypoestrogenic) and has high levels of FSH
and LH
. Estrogen
and progesterone
therapy is usually then commenced.
. In the latter a distinct chromosomal aberration is present, while in PGD the chromosomal constellation is either 46,XX or 46,XY. Thus XX gonadal dysgenesis is also referred to as PGD, 46 XX, and XY gonadal dysgenesis as PGD, 46,XY or Swyer syndrome
. Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations.
have been reported. Apparently either the germ cells do not form or interact with the gonadal ridge or undergo accelerated atresia
so that at the end of childhood only a streak gonad is present, unable to induce pubertal changes. As girls' ovaries produce no important body changes before puberty
, there is usually no suspicion of a defect of the reproductive system until puberty fails to occur.
Familial cases of XX gonadal dysgenesis are on record.
In one family mutations in the mitochondrial histidyl tRNA synthetase have been described as the cause.
s and androgen
s), most of the secondary sex characteristic
s do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods
. Because the adrenal gland
s can make limited amounts of androgens and are not affected by this syndrome, most of these girls will develop pubic hair, though it often remains sparse.
Evaluation of delayed puberty
usually reveals the presence of pubic hair, but elevation of gonadotropin
s, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a karyotype
and imaging of the pelvis. The karyotype reveals XX chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). At this point it is usually possible for a physician to make a diagnosis of XX gonadal dysgenesis.
inasmuch as both conditions have the same phenotype and clinical issues; however in Swyer syndrome the karyotype is 46,XY, and thus gonadectomy is recommended.
In Turner syndrome
there is a demonstrable abnormality in or absence of one of the sex chromosomes that is the cause of the development of gonadal dysgenesis. In contrast XX gonadal dysgenesis has a normal female chromosome situation.
Another type of XX gonadal dysgenesis is known as 46,XX gonadal dysgenesis epibulbar dermoid, which follows the similar symptoms as the regular syndrome, though it also shows signs of epibulbar dermoid (eye disorder). It has been suggested to be a new type of syndrome.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
disease. It affects both males and females but the phenotype differs. In both sexes sensorineural deafness occurs but in females ovarian dysgenesis also occurs.
XX gonadal dysgenesis is a type of female hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
in which no functional ovaries are present to induce puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
in an otherwise normal girl whose karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
is found to be 46,XX. With nonfunctional streak ovaries she is low in estrogen levels (hypoestrogenic) and has high levels of FSH
FSH
FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...
and LH
LH
LH, Lh, or lh may stand for:*Laurel and Hardy*Leasehold *Left-handed or left hand*Letterhead, the heading at the top of a sheet of letter paper*lh, a digraph for many languages...
. Estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
therapy is usually then commenced.
XX GD as a form of “pure gonadal dysgenesis”
The term “pure gonadal dysgenesis” (PGD) has been used to distinguish a group of patients from gonadal dysgenesis related to Turner syndromeTurner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
. In the latter a distinct chromosomal aberration is present, while in PGD the chromosomal constellation is either 46,XX or 46,XY. Thus XX gonadal dysgenesis is also referred to as PGD, 46 XX, and XY gonadal dysgenesis as PGD, 46,XY or Swyer syndrome
Swyer syndrome
Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty...
. Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations.
Pathogenesis
The cause of the condition is often unclear. There are cases where abnormalities in the FSH-receptorFSH-receptor
The follicle-stimulating hormone receptor or FSH-receptor is a transmembrane receptor that interacts with the follicle-stimulating hormone and represents a G protein-coupled receptor . Its activation is necessary for the hormonal functioning of FSH...
have been reported. Apparently either the germ cells do not form or interact with the gonadal ridge or undergo accelerated atresia
Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
so that at the end of childhood only a streak gonad is present, unable to induce pubertal changes. As girls' ovaries produce no important body changes before puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, there is usually no suspicion of a defect of the reproductive system until puberty fails to occur.
Familial cases of XX gonadal dysgenesis are on record.
In one family mutations in the mitochondrial histidyl tRNA synthetase have been described as the cause.
Perrault syndrome
In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now called Perrault syndrome.Diagnosis
Because of the inability of the streak gonads to produce sex hormones (both estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s and androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s), most of the secondary sex characteristic
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
s do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
. Because the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s can make limited amounts of androgens and are not affected by this syndrome, most of these girls will develop pubic hair, though it often remains sparse.
Evaluation of delayed puberty
Delayed puberty
Puberty is described as delayed puberty with exceptions when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay, a...
usually reveals the presence of pubic hair, but elevation of gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
and imaging of the pelvis. The karyotype reveals XX chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). At this point it is usually possible for a physician to make a diagnosis of XX gonadal dysgenesis.
Treatment
The consequences to the girl with XX gonadal dysgenesis:- Her gonads cannot make estrogen, so her breasts will not develop and her uterus will not grow and menstruate until she is given estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
. This is often given through the skin now. - Her gonads cannot make progesterone, so her menstrual periods will not be predictable until she is given a progestinProgestinA progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
, still usually as a pill. - Her gonads cannot produce eggsOvumAn ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
so she will not be able to conceive children naturally. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman's fertilized egg (embryo transferEmbryo transferEmbryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy...
).
Related conditions
XX gonadal dysgenesis is related to the Swyer syndromeSwyer syndrome
Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty...
inasmuch as both conditions have the same phenotype and clinical issues; however in Swyer syndrome the karyotype is 46,XY, and thus gonadectomy is recommended.
In Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
there is a demonstrable abnormality in or absence of one of the sex chromosomes that is the cause of the development of gonadal dysgenesis. In contrast XX gonadal dysgenesis has a normal female chromosome situation.
Another type of XX gonadal dysgenesis is known as 46,XX gonadal dysgenesis epibulbar dermoid, which follows the similar symptoms as the regular syndrome, though it also shows signs of epibulbar dermoid (eye disorder). It has been suggested to be a new type of syndrome.