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Genetics Home Reference: your guide to understanding genetic conditions
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48,XXYY syndrome

Reviewed January 2010

What is 48,XXYY syndrome?

48,XXYY syndrome is a chromosomal condition that causes medical and behavioral problems in males.

48,XXYY disrupts male sexual development. Adolescent and adult males with this condition typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development. A shortage of testosterone during puberty can lead to reduced facial and body hair, poor muscle development, low energy levels, and an increased risk for breast enlargement (gynecomastia). Because their testes do not function normally, males with 48, XXYY syndrome have an inability to father children (infertility).

48,XXYY syndrome can affect other parts of the body as well. Males with 48,XXYY syndrome are often taller than other males their age. They tend to develop a tremor that typically starts in adolescence and worsens with age. Dental problems are frequently seen with this condition; they include delayed appearance of the primary (baby) or secondary (adult) teeth, thin tooth enamel, crowded and/or misaligned teeth, and multiple cavities. As affected males get older, they may develop a narrowing of the blood vessels in the legs, called peripheral vascular disease. Peripheral vascular disease can cause skin ulcers to form. Affected males are also at risk for developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the legs. Additionally, males with 48,XXYY syndrome may have flat feet (pes planus), elbow abnormalities, allergies, asthma, type 2 diabetes, seizures, and congenital heart defects.

Most males with 48,XXYY syndrome have some degree of difficulty with speech and language development. Learning disabilities, especially reading problems, are very common in males with this disorder. Affected males seem to perform better at tasks focused on math, visual-spatial skills such as puzzles, and memorization of locations or directions. Some boys with 48,XXYY syndrome have delayed development of motor skills such as sitting, standing, and walking that can lead to poor coordination. Affected males have higher than average rates of behavioral disorders, such as attention deficit hyperactivity disorder (ADHD); mood disorders, including anxiety and bipolar disorder; and/or autism spectrum disorders, which affect communication and social interaction.

How common is 48,XXYY syndrome?

48,XXYY syndrome is estimated to affect 1 in 18,000 to 50,000 males.

What are the genetic changes related to 48,XXYY syndrome?

48,XXYY syndrome is a condition related to the X and Y chromosomes (the sex chromosomes). People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). 48,XXYY syndrome results from the presence of an extra copy of both sex chromosomes in each of a male's cells (48,XXYY). Extra copies of genes on the X chromosome interfere with male sexual development, preventing the testes from functioning normally and reducing the levels of testosterone. Many genes are found only on the X or Y chromosome, but genes in areas known as the pseudoautosomal regions are present on both sex chromosomes. Extra copies of genes from the pseudoautosomal regions of the extra X and Y chromosome contribute to the signs and symptoms of 48,XXYY syndrome; however, the specific genes have not been identified.

Related Chromosome(s)

Changes involving these chromosomes are associated with 48,XXYY syndrome.

  • X chromosome
  • Y chromosome

Can 48,XXYY syndrome be inherited?

This condition is not inherited; it usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. In 48,XXYY syndrome, the extra sex chromosomes almost always come from a sperm cell. Nondisjunction may cause a sperm cell to gain two extra sex chromosomes, resulting in a sperm cell with three sex chromosomes (one X and two Y chromosomes). If that sperm cell fertilizes a normal egg cell with one X chromosome, the resulting child will have two X chromosomes and two Y chromosomes in each of the body's cells.

In a small percentage of cases, 48,XXYY syndrome results from nondisjunction of the sex chromosomes in a 46,XY embryo very soon after fertilization has occurred. This means that an normal sperm cell with one Y chromosome fertilized a normal egg cell with one X chromosome, but right after fertilization nondisjunction of the sex chromosomes caused the embryo to gain two extra sex chromosomes, resulting in a 48,XXYY embryo.

Where can I find information about diagnosis or management of 48,XXYY syndrome?

You might find information on the diagnosis or management of 48,XXYY syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/48xxyy-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/48xxyy-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about 48,XXYY syndrome?

You may find the following resources about 48,XXYY syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

    What other names do people use for 48,XXYY syndrome?

    • XXYY syndrome

    For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

    What if I still have specific questions about 48,XXYY syndrome?

    Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

    What glossary definitions help with understanding 48,XXYY syndrome?

    ADHD ; adolescent ; aneuploidy ; anxiety ; attention deficit hyperactivity disorder ; autism ; bipolar disorder ; cell ; cell division ; chromosome ; congenital ; diabetes ; disabilities ; egg ; embryo ; enamel ; gynecomastia ; hormone ; hyperactivity ; hypogonadism ; infertility ; inherited ; motor ; nondisjunction ; peripheral ; puberty ; reproductive cells ; sex chromosomes ; spectrum ; sperm ; syndrome ; testes ; testosterone ; thrombosis ; tremor ; vascular ; veins

    You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

    References

    • Tartaglia N, Borodyanskaya M, Hall DA. Tremor in 48,XXYY syndrome. Mov Disord. 2009 Oct 15;24(13):2001-7. doi: 10.1002/mds.22700. Erratum in: Mov Disord. 2010 Aug 15;25(11):1764. Borodyanskya, Mariya [corrected to Borodyanskaya, Mariya]. (http://www.ncbi.nlm.nih.gov/pubmed/19705466?dopt=Abstract)
    • Tartaglia N, Davis S, Hench A, Nimishakavi S, Beauregard R, Reynolds A, Fenton L, Albrecht L, Ross J, Visootsak J, Hansen R, Hagerman R. A new look at XXYY syndrome: medical and psychological features. Am J Med Genet A. 2008 Jun 15;146A(12):1509-22. doi: 10.1002/ajmg.a.32366. (http://www.ncbi.nlm.nih.gov/pubmed/18481271?dopt=Abstract)
    • Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis. 2006 Oct 24;1:42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17062147?dopt=Abstract)
    • Visootsak J, Rosner B, Dykens E, Tartaglia N, Graham JM Jr. Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY. Am J Med Genet A. 2007 Jun 1;143A(11):1198-203. (http://www.ncbi.nlm.nih.gov/pubmed/17497714?dopt=Abstract)
    • Zelante L, Piemontese MR, Francioli G, Calvano S. Two 48,XXYY patients: clinical, cytogenetic and molecular aspects. Ann Genet. 2003 Oct-Dec;46(4):479-81. (http://www.ncbi.nlm.nih.gov/pubmed/14659786?dopt=Abstract)

     

    The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

     
    Reviewed: January 2010
    Published: October 20, 2014