Ovotesticular syndrome (also known as ovotesticular disorder or OT-DSD) is a rare congenital condition of atypical sexual differentiation where an individual is born with both ovarian and testicular tissue. It is one of the rarest disorders of sex development, with an incidence rate of approximately one in 100,000 live births. Commonly, one or both gonads is an ovotestis containing both types of tissue. Although it is similar in some ways to mixed gonadal dysgenesis, the conditions can be distinguished histologically.
People with ovotesticular syndrome may be considered intersex.

Terminology

Hermaphrodite

The term hermaphrodite means a single organism that has both male and female reproductive organs or a single organism that can produce both male and female gametes (sperm and ova), which is extremely rare in humans.
In the past, prior to the 2006 Chicago consensus statement, ovotesticular syndrome was referred to as true hermaphroditism, which is now considered outdated, and is also considered misleading or stigmatizing by some medical and advocacy groups. Some intersex people have chosen to reclaim the word hermaphrodite and use it as a self-descriptor.

Disorder

Pathologizing language, including the term disorders of sex development, can also sometimes be seen as controversial or stigmatizing, due to the claim that it frames the simultaneous presence of ovarian and testicular tissue and corresponding hormonally induced sex characteristic development in a healthy individual as disordered rather than a natural variation of human sexual development.

Presentation

Physical

Some people with ovotesticular syndrome may appear phenotypically normal or present with no obvious symptoms. Other times the following may be found:

Presence or development of mixed sex characteristics, androgynous phenotype
Feminization of a boy/man or masculinization of a girl/woman, especially at puberty
Hyperandrogenism in a woman or hypoandrogenism in a man
Hyperestrogenism in a man or hypoestrogenism in a woman
Enlargement of one or both breasts in men (gynecomastia) (present in 75% of cases) or underdeveloped breasts in women (micromastia)
Hirsutism or male pattern hair loss in women, or lack of terminal hair growth in men
Small phallus midway in size between a clitoris and a penis (clitoromegaly, micropenis, or ambiguous genitalia)
Incompletely closed urogenital opening or persistent urogenital sinus
Hypospadias, chordee, or incomplete labialscrotal fusion
Cryptorchidism or other gonad anomalies such as testicles or ovaries that appear unusually large or small, atypically placed, or asymmetrical (which may in some cases be an ovotestis)
Prostate or wolffian anomalies such as prostate hypoplasia or degradation/absence of either of the vas deferens, seminal vesicles, or epididymis (largely due to the necessity of testicular production of testosterone and dihydrotestosterone in maintaining and developing the prostate and wolffian structures in utero)
Uterine or müllerian anomalies such as unicornuate uterus, uterine hypoplasia, or fallopian tubes that are degraded or missing (largely due anti-müllerian hormone being produced by testicular tissue in utero causing degradation of müllerian structures)
Anomalies of the vagina or vulva such as vaginal hypoplasia, vaginal atresia, or labia minora that are absent or underdeveloped (largely due to testicular production of testosterone and dihydrotestosterone controlling the fusion and masculinization of the labialscrotal folds, genital tubercle, urethra, and lower 1/3 of the vaginal canal/urogenital sinus including the vaginal introitus)
Hematuria, hematospermia, or hematometra
Amenorrhea, delayed menarche, oligomenorrhea, or other menstrual irregularities
Infertility such as azoospermia or anovulation
Heterochromia, heterotrichosis, or atypical areas of skin pigmentation (especially following blaschko's lines) in cases originating from mosaicism or chimerism

Cognitive

Studies on the limited amount of cases show the condition does not cause cognitive impairment.

Psychological

Individuals with ovotesticular syndrome may struggle with minority stress, social avoidance, social isolation, agoraphobia, anxiety, depression, shame, body image issues, gender identity issues, sexual dysfunction, self esteem issues, dissociation, or feelings of being disconnected from their body. They may struggle with medical mistrust and healthcare avoidance.

Gender

People with ovotesticular syndrome are more likely to experience gender dysphoria or gender identity related issues than the average person. People with ovotesticular syndrome may identify as intersex or intergender, and are more likely than the average population to identify as nonbinary/gender nonconforming, transgender, or queer. They are more likely to identify as nonbinary/gender nonconforming or queer than they are to identify as transgender.

Causes

There are several ways in which this may occur.

It can be caused by the division of one ovum, 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.

Variations

Ovotesticular syndrome occurs in 4 different variations:

Bilateral - both ovarian and testicular tissue appear on both sides.
Unilateral - on one side there is an ovotestis (a gonad with 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 on opposite sides.
Indeterminate - it is known that the condition is present, but it is not evident where the ovary and testicular tissue is located.

Karyotypes

An 46,XX karyotype is the most common (55-80% of cases); most individuals with this form are SRY negative. A 46,XX/,46XY karyotype appears in 20-30% of cases and an 46,XY karyotype in 5-15% of cases. Presence of 46,XX/46,XY chimerism has been recorded in between 13% and 30% of cases. Some degree of mosaicism is present in about 25% of cases. Encountered karyotypes include 46,XX/46,XY, or 46,XX/47,XXY or XX & XY with SRY mutations, mixed chromosomal anomalies or hormone deficiency/excess disorders, 47,XXY.

Prevalence
Ovotesticular syndrome represents 5% of all disorders of sex development. It is one of the rarest disorders of sex development, with an incidence rate of approximately one in 100,000 live births. By 1991 approximately 500 case studies had been performed.

Fertility

The gonad most likely to function is the ovary. The ovotestes show evidence of ovulation in 50% of cases. Spermatogenesis has only been observed in solitary testes and not in the testicular portions of ovotestes. According to a 1994 study, spermatogenesis 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 females 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 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

Military

United States

Having ovotesticular syndrome can make one inadmissible for service in the United States Armed Forces if undiagnosed and untreated. Waivers are possible on a case by case basis.

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, 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, "The reconstruction of female genitalia (via surgeries such as a vaginoplasty or clitoridectomy) 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, 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 for $440,000. The university denied negligence, but agreed to a "compromise" settlement to avoid "costs of litigation."

People with ovotesticular syndrome
Cheryl Chase
Foekje Dillema
Anton Krzyzanowski
Aleksa Vulović

See also
Ovotestis
Development of the gonads
Sexual differentiation in humans
Disorders of sex development
Intersex
Intergender
Sex characteristics
Sex characteristics (legal term)
Androgynos (Judaism)
Androgynos (Mythology)
Androgyny
Hermaphrodite

References

External links

Media related to Intersex at Wikimedia Commons