46, XY disorders of sexual development

Typical sex development requires multiple genes, hormones, and hormone receptors to work in concert. 46, XY disorders of sex development (DSD) are caused by either disorders of testicular development or disorders involving the male hormone, androgen. Conditions which fall within the spectrum of 46, XY DSD, include:

• 46, XY complete gonadal dysgenesis (Swyer syndrome)
• 46 XY, partial gonadal dysgenesis (Denys-Drash syndrome, Frasier syndrome)
• Ovotesticular DSD
• Testicular regression syndrome (vanishing testes syndrome)
• Leydig cell aplaisa/hypoplasia (due to hCG/LH receptor abnormalities)

• T biosynthesis defects

  • STAR deficiency
  • P450scc deficiency
  • 3-b hydroxysteroid dehydrogenase type II deficiency
  • 17a-hydroxylase and 17,20-lyase deficiency
  • Isolated 17,20-lyase deficiency
  • P450 oxidoreductase "POR gene" defect
  • 17b-hydroxysteroid dehydrogenase III deficiency

• POR gene abnormality (defective 17,20-lyase activity of P450c17)

• Persistent Mullerian duct syndrome (AMH or AMH-receptor genes abnormality)
• 5 alpha-reductase type 2 deficiency
• Complete and partial androgen insensitivity syndromes

People with 46, XY disorders of sex development (DSD) benefit from having a multidisciplinary team of healthcare providers. Initial work-up involves taking a family history, pregnancy history, and a physical exam. This information, combined with chromosome test results, guides additional testing. Additional tests may include hormone measurements (e.g., LH, FSH, inhibin B, T, DHT, AMH, A, and DHEAS), imaging (e.g., ultrasound), biopsy, and genetic testing.

People with 46, XY disorders of sex development (DSD) receive care from a variety of specialists. Geneticists, neonatologists, endocrinologists, gynaecologists, psychiatrists, surgeons, and social workers may be part of this team. If you have not already done so, we suggest you speak with your healthcare provider regarding appropriate referrals.

To read about different types of specialists and what they do, you can visit the following link to Harvard Medical School’s Family Health Guide:
http://www.health.harvard.edu/fhg/specialists.shtml

You can find a list of directories to help you find health professionals, services, and facilities by visiting the MedlinePlus.gov Web page at the following link.
http://www.nlm.nih.gov/medlineplus/directories.html

The following online resources can help you find a genetics professional in your community:

• GeneTests has a searchable directory of US and international genetics and prenatal diagnosis clinics.
• The National Society of Genetic Counselors provides a searchable directory of US and international genetic counseling services.
• The American College of Medical Genetics has a searchable database of US genetics clinics.
• The University of Kansas Medical Center provides a list of US and international genetic centers, clinics, and departments.
• The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.

The following support groups may also be able to direct you to local resources and specialists:

Accord Alliance
531 Route 22 East #244
Whitehouse Station, NJ 08889
Telephone: 908-349-0534
Fax: 801-349-0534
E-mail: http://www.accordalliance.org/contact/email-us.html
Web site: http://www.accordalliance.org/

AISSG-USA
P.O. Box 2148
Duncan, OK 75354-2148
E-mail: aissgusa@hotmail.com
Web site: www.aissgusa.org

Intersex Society of North America
979 Golf Course Drive #282
Rohnert Park CA 94928
Fax: 801-348-5350
Web site: http://www.isna.org/

Further tips for finding experts is available on our Web site at the following link:
http://rarediseases.info.nih.gov/GARD/FindAnExpert.aspx

A 46, XY disorder of sex development (DSD) is a condition in which an individual with one X chromosome and one Y chromosome in each cell, the pattern normally found in males, have genitalia that is not clearly male or female. Infants with this condition tend to have penoscrotal hypospadias, abnormal development of the testes, and reduced to no sperm production. Some individuals with 46, XY DSD have fully to underdeveloped female reproductive organs (e.g., uterus and fallopian tubes), while others do not. People with with 46, XY DSD may be raised as males or females. Treatment involves surgery and hormone replacement therapy. People with 46, XY DSD are at an increased risk for gonadal tumors and benefit from regular surveillance or surgery to remove abnormally developed gonads.

As you can read in our GARD webpages, the 46, XY disorders are a group of different conditions including 46, XY complete gonadal dysgenesis (Swyer syndrome), 46 XY, partial gonadal dysgenesis (Denys-Drash syndrome, Frasier syndrome), ovotesticular DSD, testicular regression syndrome (vanishing testes syndrome) , Leydig cell aplaisa/hypoplasia, testosterone biosynthesis defects, POR gene abnormality, persistent Mullerian duct syndrome, 5 alpha-reductase type 2 deficiency and complete and partial androgen insensitivity syndromes.

Therefore, several biologic factors such as genetic and hormonal influences contribute to gender identity, gender role behavior, and sexual orientation in humans, but this relationship is also modified by psychological, social, and cultural factors. Sex assignment of children with ambiguous genitalia remains a difficult decision for the families involved and subject to controversial discussion among professionals and self-help groups. Every case is unique and it is suggested that gender assignment should be based on clinical experience, study of the literature, and interviews with affected individuals.

In a large study recently published about women with complete androgen insensitivity syndrome (CAIS) it was found that they perceive themselves as highly feminine throughout development. Additionally, CAIS women largely report their sexual attraction, fantasies, and experiences were best described as female heterosexual. CAIS women unanimously reported satisfaction with being a woman (100%). Another study with 46, XY individuals with androgen secreting testicular tissue and 46, XX individuals with congenital adrenal hyperplasia concluded that androgen exposure may have some effect in higher brain function and the perception of the gender. The authors suggested that gender counseling should be part of the routine management for these patients to make sure that they are happy with being females.

The World Health Organization provides relevant information about gender and genetics in the following links: Genetic Components of Sex and Gender
Gender Assignment of Intersex Infants and Children
Legal Definitions of Gender

Gönül Öçal. Current Concepts in Disorders of Sexual Development. Clin Res Pediatr Endocrinol. 2011 September; 3(3):105–114.