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Disease Profile

46,XX testicular disorder of sex development

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adolescent

ICD-10

Q99.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

46,XX testicular DSD; 46,XX gonadal dysgenesis; XX male syndrome;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Kidney and Urinary Diseases;

Summary

46,XX testicular disorder of sex development is a condition in which a person with two X chromosomes (which is normally found in females) has a male appearance. More specifically, people with this condition have male external genitalia, ranging from normal to ambiguous. Other common signs and symptoms include small testes, gynecomastia, infertility due to azoospermia (lack of sperm), and health problems related to low testosterone. Less often, affected people may experience abnormalities such as undescended testes and hypospadias. Gender role and gender identity are normally reported as male.[1][2] This condition may occur if the SRY gene (which is usually found on the Y chromosome) is misplaced onto the X chromosome. This generally occurs to do an abnormal exchange of genetic material between chromosomes (a translocation). Less commonly, the condition may be due to copy number variants or rearrangements in or around the SOX9 or SOX3 gene. In some affected people, the underlying cause is unknown. In most cases, the condition occurs sporadically in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person and generally includes testosterone replacement therapy.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Male hypogonadism
Decreased function of male gonad
0000026
Polycystic ovaries
0000147
5%-29% of people have these symptoms
Ovotestis
0012861
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Azoospermia
Absent sperm in semen
0000027
Bifid scrotum
Cleft of scrotum
0000048
Decreased serum testosterone level
Decreased serum testosterone levels
Low serum testosterone level
Low serum testosterone levels

[ more ]

0040171
Hypoplasia of the uterus
Small uterus
Underdeveloped uterus

[ more ]

0000013
Hypoplasia of the vagina
Underdeveloped vagina
0008726
Micropenis
Short penis
Small penis

[ more ]

0000054
Perineal hypospadias
0000051
Scrotal hypoplasia
Smaller than typical growth of scrotum
0000046
Sex reversal
0012245
True hermaphroditism
0010459

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on 46,XX testicular disorder of sex development. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss 46,XX testicular disorder of sex development. Click on the link to view a sample search on this topic.

          References

          1. Emmanuèle C Délot, PhD and Eric J Vilain, MD, PhD, FACMG. Nonsyndromic 46,XX Testicular Disorders of Sex Development. GeneReviews. May 2015; https://www.ncbi.nlm.nih.gov/books/NBK1416/#xxms.Clinical_Characteristics.
          2. 46,XX testicular disorder of sex development. Genetics Home Reference. November 2008; https://ghr.nlm.nih.gov/condition/46xx-testicular-disorder-of-sex-development.