NORD gratefully acknowledges 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 patients. 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. In patients with 46, XX, there have been a small number of cases reported with genetic variations of other genes such as, duplication of SOX9, mutations in RSPO1, and a specific mutation in the NR5A1 gene. In the more rare individuals with ovotesticular DSD who have a Y chromosome (which normally results in male sexual development), deletions of DMRT1, mutations of SRY and mutations of MAP3K1 have been reported, as well as 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.
Ovotesticular DSD is diagnosed by a combination of tests including chromosome and genetic analysis, hormone testing, ultrasound or MRI and gonadal biopsy.
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.
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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
695 Charles Young Drive South
Los Angeles, CA 90095-7088
Phone: (310) 267-2455
Fax: (310) 794-5446
Arboleda VA, Sandberg DE, Vilain E. DSDs: genetics, underlying pathologies and psychosexual differentiation.Nat Rev Endocrinol. 2014;Oct;10(10):603-15. doi: 10.1038/nrendo.2014.130. Epub 2014 Aug 5.
Vilain E. The genetics of ovotesticular disorders of sex development. Adv Exp Med Biol. 2011;707:105-6. doi: 10.1007/978-1-4419-8002-1_22.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. Medscape. Last Update November 12, 2014. http://emedicine.medscape.com/article/1015520-overview Accessed August 9, 2016.
Medline Plus: A Service of the U.S. National Library of Medicine and the National Institutes of Health. Medical encyclopedia: Intersex. Last Update 7/10/2015. https://medlineplus.gov/ency/article/001669.htm. Accessed August 9, 2016.
Ahmed F, Lucas-Herald A, McGowan R, Tobias E. Orphanet. Last Update January 2014. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2138 Accessed August 9, 2016.
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