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NORD is very grateful to Eric Vilain, MD, PhD, Professor of Human Genetics, Pediatrics and Urology; Director, Center for Gender-Based Biology; Chief, Medical Genetics, Department of Pediatrics; David Geffen School of Medicine at UCLA, for assistance in the preparation of this report.
Ovotesticular disorder of sex development (ovotesticular DSD) is a very rare disorder in which an infant is born with the internal reproductive organs (gonads) of both sexes (female ovaries and male testes). The gonads can be any combination of ovary, testes or combined ovary and testes (ovotestes). The external genitalia are usually ambiguous but can range from normal male to normal female.
Ovotesticular DSD is characterized by the presence of both ovarian and testicular tissue in the same individual. An ovotestis is present in approximately 2/3 of affected individuals.
An abnormal vagina is often present and if a uterus is present it is usually underdeveloped (hypoplastic). If a penis is present, it may show an abnormality in which the canal (urethra) that carries urine from the bladder opens on the underside (hypospadias). When testes are present, they are usually undescended (cryptorchidism).
Upon reaching puberty, breast development, feminization and menstruation may occur. Most affected individuals are infertile but ovulation or spermatogenesis is possible.
Tumors of the ovaries or testes have been reported but are rare.
The exact cause of ovotesticular DSD is known only in a small percentage of cases. Most affected individuals have a 46,XX chromosomal make-up (karyotype), which normally results in female sexual development. In about 10% of patients, testicular tissue in an individual with a 46,XX karyotype is present as a result of a translocation of the SRY gene on the Y chromosome to the X chromosome or another chromosome. There have been a small number of cases reported with genetic variations of other genes such as deletion of DMRT1, duplication of SOX9, mutaions in RSPO1. Some rare individuals with ovotesticular DSD have a 46,XY karyotype (which normally results in male sexual development) or a karyotype that shows some cells with XY chromosomes and others with XX chromosomes (XX/XY mosaicism).
Chromosomes are located in the nucleus of human cells and carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Normally, males have one X and one Y chromosome and females have two X chromosomes.
Ovotesticular DSD is the rarest disorder of sex development in humans and has an approximate incidence of less than 1/20,000. At least 500 affected individuals have been reported.
Symptoms of the following disorders can be similar to those of ovotesticular DSD. Comparisons may be useful for a differential diagnosis:
Klinefelter syndrome is a group of chromosomal disorders in males in which one or more extra X chromosomes are present. Males with the classic form of the disorder have one extra X chromosome. Males with variant forms of Klinefelter syndrome have additional X and/or Y chromosomes. The extra X and/or Y chromosome can effect physical and intellectual development. Common physical features may include small testes (hypogonadism), delayed pubertal development, and breast development (gynecomastia) in late puberty. These features may be associated with low testosterone level and elevated gonadotropin levels. (For more information on this disorder, choose "Klinefelter" as your search term in the Rare Disease Database.)
46, XX disorder of sexual development is a disorder in which the chromosomes are 46, XX (normal female) and ovaries are present but external genitalia appear male. This usually occurs when a female embryo is exposed to excessive amounts of male hormones while in the uterus. The internal female reproductive glands are usually normal while the external genitalia are male, or a combination of male and female. The clitoris may be enlarged and there may be one common outlet for the urethra and vagina. Other symptoms may include absence of breast development, excessive growth of hair in abnormal areas (hirsutism), increased muscularity, absent or irregular menstruation (amenorrhea), obesity, a short and thick neck, protruding abdomen and thin arms and legs. 46, XX DSD can be caused by genetic disorders such as congenital adrenal hyperplasia or aromatase deficiency, the presence of a tumor in the mother that produces male hormones or male hormones taken by the mother during pregnancy.
46, XY disorder of sexual development (formerly called male pseudohermaphroditism) is a disorder in which the chromosomes are 46, XY (normal male) but external genitalia are underdeveloped, ambiguous or female. This disorder can be caused by genetic abnormalities, abnormal testicular development or abnormal testosterone production.
Mixed gonadal dysgenesis is the diagnosis given when individuals have a well-developed gonad (ovary or testis) on one side and an underdeveloped (streak) gonad on the other side.
Ovotesticular DSD is diagnosed by a combination of tests including chromosome analysis, hormone testing, ultrasound and MRI.
A team of professionals with experience in treating disorders of sex development should work together to treat a child with ovotesticular DSD.
Recommendations about treatment have evolved in recent years. Gender assignment remains recommended in the neonatal period, based on the appearance of the external genitalia, the formation of the internal reproductive glands, the potential for fertility and the available medical literature. But lack of outcome data has led to challenge the practice of early genital surgery.
Some experts now suggest delaying surgery and involving the child in decision-making if possible. Factors to consider include the ability to reconstruct functioning genitals as well as psychological, behavioral, chromosomal, hormonal and neural factors.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
Contact for additional information about ovotesticular disorder of sex development:
Eric Vilain, M.D., Ph.D.
Professor of Human Genetics, Pediatrics and Urology
Director, Center for Gender-Based Biology
Chief, Medical Genetics, Department of Pediatrics
David Geffen School of Medicine at UCLA
Gonda Center, Room 5506
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Los Angeles, CA 90095-7088
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Wiersma R. The clinical spectrum and treatment of ovotesticular disorder of sexual development. Adv Exp Med Biol. 2011;707:101-3.
Hughes IA, Houk C, Ahmed SF, Lee PA; Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2(3):148-62.
Kim KR, Kwon Y, Joung JY, Kim KS, Ayla AG and Ro JY. True hermaphroditism and mixed gonadal dysgenesis in young children: A clinicopathologic study of 10 cases. Modern Pathology. 2002; 15(10):1013-1.
Hutcheson J, Snyder III HM. Ambiguous Genitalis and Intersexuality. Emedicine. http://emedicine.medscape.com/article/1015520-overview . Updated January 11, 2012. Accessed August 30, 2012.
Medline Plus: A Service of the U.S. National Library of Medicine and the National Institutes of Health. Medical encyclopedia: Intersex. www.nlm.nih.gov/medlineplus/ency/article/001669. Updated August 2, 2011. Accessed August 30, 2012.
Last Updated February 2005. Accessed August 30, 2012.
Report last updated: 2012/09/04 00:00:00 GMT+0