Ovotesticular syndrome (also known as ovotesticular disorder or OT-DSD) is a rare congenital condition where an individual is born with both
ovarian and
testicular tissue.
It is one of the rarest
disorders of sex development
Disorders of sex development (DSDs), also known as differences in sex development, variations in sex characteristics (VSC), sexual anomalies, or sexual abnormalities, are congenital conditions affecting the reproductive system, in which developme ...
(DSDs), with only 500 reported cases.
Commonly, one or both
gonad
A gonad, sex gland, or reproductive gland is a Heterocrine gland, 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 gon ...
s is an
ovotestis
An ovotestis is a gonad with both Testicle, testicular and Ovary, ovarian aspects. In humans, ovotestes are an infrequent anatomical variation associated with gonadal dysgenesis. The only mammals where ovotestes are not characteristic of an infrequ ...
containing both types of tissue.
Although it is similar in some ways to
mixed gonadal dysgenesis
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 aneuploidy and mosaicism of the Y chromosome. It is a fairly rare chromosomal disorder a ...
, the conditions can be distinguished histologically.
Terminology
In the past, ovotesticular syndrome was referred to as true hermaphroditism, which is considered outdated as of 2006. The term "true hermaphroditism" was considered very misleading by many medical organizations and by many advocacy groups,
as
hermaphroditism refers to a species that produces both
sperm
Sperm (: sperm or sperms) is the male reproductive Cell (biology), cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm ...
and
ova, something that is impossible in humans.
Symptoms
Physical
* Enlargement of one or both breasts in men (
gynecomastia
Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...
) (present in 75% of cases)
* Small
phallus
A phallus (: phalli or phalluses) is a penis (especially when erect), an object that resembles a penis, or a mimetic image of an erect penis. In art history, a figure with an erect penis is described as ''ithyphallic''.
Any object that symbo ...
midway in size between a
clitoris
In amniotes, the clitoris ( or ; : clitorises or clitorides) is a female sex organ. In humans, it is the vulva's most erogenous zone, erogenous area and generally the primary anatomical source of female Human sexuality, sexual pleasure. Th ...
and a
penis
A penis (; : penises or penes) is a sex organ through which male and hermaphrodite animals expel semen during copulation (zoology), copulation, and through which male placental mammals and marsupials also Urination, urinate.
The term ''pen ...
* Incompletely closed
urogenital opening
The urogenital opening is where bodily waste and reproductive fluids are expelled to the environment outside of the body cavity. In some organisms, including monotremes, birds and some fish, discharge from the urological, digestive, and reprod ...
(shallow
vagina
In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
)
* Abnormal urethra opening on the
perineum
The perineum (: perineums or perinea) in placentalia, placental mammals is the space between the anus and the genitals. The human perineum is between the anus and scrotum in the male or between the anus and vulva in the female. The perineum is ...
Cognitive
Studies on the limited amount of cases on ovotesticular syndrome shows the condition does not cause cognitive impairment.
Causes
There are several ways in which this may occur.
* It can be caused by the division of one
ovum
The egg cell or ovum (: ova) is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is not capa ...
, followed by fertilization of each haploid ovum and fusion of the two
zygotes early in development
* Single gene mutations.
* Alternately, an ovum can be fertilized by two sperm followed by
trisomic rescue in one or more daughter cells.
* Two ova fertilized by two sperm cells will occasionally fuse to form a tetragametic
chimera, if one male zygote and one female zygote fuse.
* It can be associated with a mutation in the
SRY gene.
* Etc.
** Mitotic or meiotic errors: Can cause sex chromosome mosaicism
** Double fertilization: Can result in 46XX/46XY chimerism, which occurs when an X sperm and a Y sperm fertilize an ovum
** Fusion of two ova: Can result in 46XX/46XY chimerism, which occurs when one male zygote and one female zygote fuse
** Mutation in the SRY gene: Can be associated with ovotesticular syndrome
** Mutation of downstream autosomal genes: Can explain SRY-negative ovotesticular syndrome
** Mutation/duplication or deletion of an X-linked locus: Can explain SRY-negative ovotesticular syndrome
** Depression of autosomal testis-determining genes: Can explain 46,XX true hermaphroditism
• Only 3 reports exist attributing specific cases of the condition to some form of duplication of the SOX9 gene; making this an incredibly rare cause.
''Note:'' ''The SRY gene has a 8 to 10% of showing up in those that are found to have ovotesticular syndrome. Due to the genetic makeup of an SRY gene, it implies that ovotesticular syndrome is more of a heterogeneous condition.''
Variations
It is documented to show up in 4 different variations. Those being Bilateral, Unilateral, Lateral, and Indeterminate.
*
Bilateral - both the ovaries and testicle tissues appear on both sides.
*
Unilateral - on one side there is what is known as ''ovotestis'' (both ovary and testicle tissue), and the other side has either ovary tissue or testicular tissue - ''not both''.
*
Lateral - both testicular and ovary tissue are present, but are on opposite sides.
*
Indeterminate - it is known that the condition is present, but it isn't evident as to where the testicular or ovary tissue is located.
Karyotypes
In ovotesticular syndrome, XX is the most common (55-80% of cases); most individuals with this form are SRY negative.
Next most common are XX/XY (20-30% of cases) and XY (5-15% of cases), with the remainder being a variety of other chromosomal anomalies and
mosaicisms.
Some degree of mosaicism is present in about 25%.
Encountered
karyotypes include
46XX/46XY, or 46XX/47XXY or XX & XY with SRY mutations, mixed chromosomal anomalies or hormone deficiency/excess disorders,
47XXY. Less than 1% have
XX/XY chimerism.
Prevalence
Ovotesticular syndrome represents 5% of all sex disorder differentiations.
The exact number of confirmed cases is uncertain, but by 1991 approximately 500 cases had been confirmed.
It has also been estimated that more than 525 have been documented.
While it can appear anywhere in the world, and be reported or unreported, the greatest amounts reported of ovotesticular syndrome is from Africa and Europe.
Fertility
The gonad most likely to function is the ovary.
The ovotestes show evidence of
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
in 50% of cases.
Spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
has only been observed in solitary
testes
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone.
The ...
and not in the testicular portions of
ovotestes.
According to a 1994 study,
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
has only been proven in two cases.
In one of the two cases, a phenotypically male individual with XX,46/XY,46 mixture had fathered a child.
It has been estimated that 80% of cases could be fertile as
female
An organism's sex is female ( symbol: ♀) if it produces the ovum (egg cell), the type of gamete (sex cell) that fuses with the male gamete (sperm cell) during sexual reproduction.
A female has larger gametes than a male. Females and ...
s with surgery.
Documented cases of fertility
There are extremely rare cases of fertility in humans with ovotesticular syndrome.
In 1994, a study on 283 cases found 21 pregnancies from 10 individuals with ovotesticular syndrome, while one allegedly fathered a child.
As of 2010, there have been at least 11 reported cases of fertility in humans with ovotesticular syndrome in the scientific literature,
with one case of a person with XY-predominant (96%)
mosaic
A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...
giving birth.
All known offspring have been male. There has been at least one case of an individual being fertile as a male.
[
There is a hypothetical scenario, in which it could be possible for a human to self-fertilize. If a human chimera is formed from a male and female zygote fusing into a single embryo, giving an individual functional gonadal tissue of both types, such self-fertilization is feasible. Indeed, it is known to occur in non-human species where hermaphroditic animals are common and has been observed in a rabbit. However, no such case of functional self-fertilization or "true bi-sexuality" has been documented in humans.]
Society and culture
Having ovotesticular syndrome of sexual development can make one inadmissible for service in the United States Armed Forces
The United States Armed Forces are the Military, military forces of the United States. U.S. United States Code, federal law names six armed forces: the United States Army, Army, United States Marine Corps, Marine Corps, United States Navy, Na ...
.
''M.C. v. Aaronson''
The U.S. legal case of ''M.C. v. Aaronson'', advanced by intersex civil society organization interACT with the Southern Poverty Law Center
The Southern Poverty Law Center (SPLC) is an American 501(c)(3) nonprofit legal advocacy organization specializing in civil rights and public interest litigation. Based in Montgomery, Alabama, it is known for its legal cases against white ...
, was brought before the courts in 2013. The child in the case was born in December 2004 with ovotestes, initially determined as male, but subsequently assigned female and placed in the care of South Carolina Department of Social Services in February 2005. Physicians responsible for M.C. initially concluded that surgery was not urgent or necessary and M.C. had potential to identify as male or female, but, in April 2006, M.C. was subjected to feminizing medical interventions. According to the Encyclopedia Britannica
An encyclopedia is a reference work or compendium providing summaries of knowledge, either general or special, in a particular field or discipline. Encyclopedias are divided into article (publishing), articles or entries that are arranged Alp ...
, "The reconstruction of female genitalia was more readily performed than the reconstruction of male genitalia, so ambiguous individuals often were made to be female." He was adopted in December 2006. M.C. identified as male at the time the case was brought, at age eight. The defendant in the case, Dr. Ian Aaronson, had written in 2001 that "feminizing genitoplasty on an infant who might eventually identify herself as a boy would be catastrophic".
The defendants sought to dismiss the case and seek a defense of qualified immunity
In the United States, qualified immunity is a legal principle of federal law that grants government officials performing discretionary (optional) functions immunity from lawsuits for damages unless the plaintiff shows that the official violated "c ...
, but these were denied by the District Court for the District of South Carolina. In January 2015, the Court of Appeals for the Fourth Circuit reversed this decision and dismissed the complaint, stating that, it did not "mean to diminish the severe harm that M.C. claims to have suffered" but that in 2006 it was not clear that there was precedent that the surgery on a sixteen-month-old violated an established constitutional right. The Court did not rule on whether or not the surgery violated M.C.'s constitutional rights.
State suits were subsequently filed. In July 2017, it was reported that the case had been settled out of court by the Medical University of South Carolina
The Medical University of South Carolina (MUSC) is a public medical school in Charleston, South Carolina. It opened in 1824 as a small private college aimed at training physicians and has since established hospitals and medical facilities acros ...
for $440,000. The university denied negligence, but agreed to a "compromise" settlement to avoid "costs of litigation."
See also
* 46,XX/46,XY
* Intersex people and military service in the United States
The regulations regarding the service of intersex people in the United States Armed Forces are vague and inconsistent due to the wide range of human intersex conditions. The United States Armed Forces as a whole does not officially ban Intersex ...
References
External links
*
{{Congenital malformations of genital organs
Congenital disorders of genital organs
Rare diseases
Intersex variations