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XYY Syndrome

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1990, 1992, 1998, 1999, 2002, 2012

NORD is very grateful to Professor Rhoshel K. Lenroot, MD, Chair of Infant, Child, and Adolescent Psychiatry, University of New South Wales; Director of Child and Adolescent Mental Health Services, South Eastern Sydney Local Health District; Neuroscience Research Australia (NeuRA), for assistance in the preparation of this report.

Synonyms of XYY Syndrome

Disorder Subdivisions

General Discussion

Summary
XYY syndrome is a rare chromosomal disorder that affects males. It is caused by the presence of an extra Y chromosome. Males normally have one X and one Y chromosome. However, individuals with this syndrome have one X and two Y chromosomes. Affected individuals are usually very tall. Many experience severe acne during adolescence. Additional symptoms may include learning disabilities and behavioral problems such as impulsivity. Intelligence is usually in the normal range, although IQ is on average 10-15 points lower than siblings.

Introduction
In the past, there were many misconceptions about this disease. It was sometimes called the super-male disease because men with this syndrome were thought to be overly-aggressive and lacking in empathy. Recent studies have shown that this is not the case. Although individuals with XYY syndrome have an increased risk for learning disabilities and behavioral problems, they are not overly aggressive, nor are they at an increased risk of any serious mental illness. Because these boys are at a higher risk for having learning disabilities, they may benefit from speech therapy, tutoring, and general awareness of the specific issues they struggle with. Although the first years of school may be more challenging for boys with XYY syndrome, they generally go on to lead full, healthy, and normal lives.

Symptoms

Characteristics of XYY syndrome are often subtle and do not necessarily suggest a serious chromosomal disorder. Thus, males with this condition are often undiagnosed or misdiagnosed. The most common physical difference is increased height, which usually becomes apparent after the age of five or six, and results in an average height of about 6 feet, 3 inches by adulthood. Some individuals with XYY also develop severe cystic acne during adolescence. Fertility and sexual development are normal. Besides the potential for increased height, most affected individuals typically have a normal physical appearance (phenotype).

Boys with XYY syndrome typically have normal intelligence, although, on average, IQ is 10 to 15 points lower than siblings. Affected boys may exhibit mild delays in reaching developmental milestones. Learning disabilities have been reported in up to 50 percent of cases, most commonly speech delays and language problems. Reading difficulties are common due to an increased incidence of dyslexia.

In some cases, affected individuals develop behavioral problems such as an explosive temper, hyperactivity, impulsivity, defiant actions, or, in some cases, antisocial behavior. There is a higher rate of attention deficit and hyperactivity disorder and a smaller increased risk for having an autism spectrum disorder.

Causes

XYY syndrome is a rare chromosomal disorder caused by the presence of an extra Y chromosome. Normally, males have 46 chromosomes including one X and one Y chromosome. Males with XYY syndrome have 47 chromosomes, two of which are Y chromosomes. Most cases of XYY syndrome are due to a cell division error in the sperm prior to conception. Rarely, the cell division error occurs after conception resulting in a mosiac of cells with 46 chromosomes and 47 chromosomes. The exact cause for why these errors in cell division occur is not understood.

Affected Populations

XYY syndrome is a rare chromosomal disorder present at birth that affects only males. It is estimated to occur in approximately one in 1,000 live births.

Related Disorders

Symptoms of the following disorders can be similar to those of XYY syndrome. Comparisons may be useful for a differential diagnosis:

Klinefelter syndrome is associated with 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 affect physical, developmental, behavioral, and cognitive functioning. Common physical features may include tall stature, lack of secondary pubertal development, 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.)

Sotos syndrome is a variable genetic disorder characterized by excessive growth before and after birth. One of the major features of Sotos syndrome is a particular facial appearance that includes facial flushing, an abnormally prominent forehead (frontal bossing), down-slanting eyelid folds (palpebral fissures), prominent, narrow jaw, a long narrow face and a head shape that is similar to an inverted pear. Height and head circumference are measured to be greater than average for most affected children. Developmental delays are present in most children with Sotos syndrome and can include motor and language delays as well as mental retardation ranging from mild to severe. Other problems associated with Sotos syndrome include jaundice in newborns, curved spine (scoliosis), seizures, crossed eyes (strabismus), conductive hearing loss, congenital heart defects, kidney abnormalities and behavioral problems. Affected individuals also have a slightly increased risk to develop specific types of tumors. Sotos syndrome is caused by an abnormality (mutation) in the NSD1 gene. (For more information on this disorder, choose "Sotos" as your search term in the Rare Disease Database.)

Marfan syndrome is a genetic disorder that affects connective tissue, which is the material between cells of the body that gives the tissues form and strength. Connective tissue is found all over the body and multiple organ systems may be affected in individuals with Marfan syndrome. The heart and blood vessels (cardiovascular), skeletal, and eye (ocular) systems are most often affected. Major symptoms include overgrowth of the long bones of the arms and legs, abnormal side-to-side curvature of the spine (scoliosis), indentation or protrusion of the chest wall (pectus), dislocation of the lenses of the eyes (ectopia lentis), nearsightedness (myopia), widening (aneurysm) and tear (dissection) of the main artery that carries blood away from the heart (aorta), floppiness of the mitral valve (mitral valve prolapse) and backward flow of blood through the aortic and mitral valves (aortic and mitral regurgitation). The specific symptoms and the severity of Marfan syndrome vary greatly from case to case. Marfan syndrome is inherited as an autosomal dominant trait. Defects or disruptions (mutations) of the fibrillin-1 (FBN1) gene have been linked to Marfan syndrome and related disorders.. (For more information on this disorder, choose "Marfan" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
A diagnosis of XYY syndrome is made based upon a thorough clinical evaluation, a detailed patient history, and specialized tests (i.e., chromosomal analysis) that detect the presence of an extra Y chromosome (47,XYY karyotype).

A diagnosis of XYY syndrome may be made before birth (prenatally) through amniocentesis or chorionic villus sampling (CVS). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal studies performed on such fluid or tissue samples may reveal the presence of an extra Y chromosome.

Clinical Testing and Work-Up
Speech and language assessment should occur during the first 24 months. Reading assessment should occur by school age to rule out dyslexia. Behavioral assessment should be considered for children who are having difficulty with symptoms such as impulsivity, poor attention, or social skills.

Treatment
Treatment of XYY syndrome is symptomatic and supportive. Speech therapy, occupational therapy, or assistance for learning disabilities in the school setting may be of benefit. In most cases, affected individuals are very responsive to early intervention and treatment, and problems may resolve altogether within a few years. Treatment of acne may help an affected individual's self-image. Attention deficit and hyperactivity disorder, difficulties with social interactions, or other behavioral problems can be treated with therapy or medication the same as in individuals who do not have XYY.

Investigational Therapies

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 website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Contact for additional information about XYY syndrome:

Professor Rhoshel K. Lenroot, M.D.
Chair of Infant, Child, and Adolescent Psychiatry
University of New South Wales
Director of Child and Adolescent Mental Health Services
South Eastern Sydney Local Health District

Neuroscience Research Australia
Corner of Barker and Easy Streets
Randwick, Sydney NSW 2031
Australia
+61 2 9399 1089 (phone)
+61 4 3416 1044 (mobile)
+61 2 9399 1082 (fax)
r.lenroot@unsw.edu.au

XYY Syndrome Resources

Organizations:

References

JOURNAL ARTICLES
Leggett V, Jacobs P, Nation K, et al. Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Dev Med Child Neurol. 2010;52:119-129.

Ross J, Zeger M, Kushner H, et al. An extra X or Y chromosome: contrasting the cognitive and motor phenotypes in childhood in boys with 47,XYY syndrome or 47,XXY Klinefelter syndrome. Dev Disabil Res Rev. 2009;15:209-317.

Visootsak J, Graham J. Social function in multiple X and Y chromosome disorders: XXY, XYY, XXYY, XXXY. Dev Disabil Res Rev. 2009;15:328-332.

Aksglaede L, Skakkebaek N, Juul A. Abnormal sex chromosome constitution and longitudinal growth: Serum levels of insulin-like growth factor (IGF)-1, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with a 47,XXY, 47,XYY, or sex-determining region of the y chromosome (SRY)-positive 46,XX karyotypes. J Clin Endocrin Metab. 2008;93 (1):169-176.

Shi Q, Martin RH. Multicolor fluorescence in situ hybridization analysis of meiotic chromosome segregation in a 47,XYY male and a review of the literature. Am J Med Genet. 2000;93:40-6. Erratum in: Am J Med Genet. 2001;99:76.

INTERNET
47, XYY Syndrome, Genetics Home References. http://ghr.nlm.nih.gov/condition/47xyy-syndrome. Updated January 2009. Accessed October 3, 2012.

Lenroot RK. XYY Syndrome. Society For The Study Of Behavioural Phenotypes. http://www.ssbp.org.uk/site/images/stories/ssbp/downloads/XYY.pdf. 2010. Accessed October 3, 2012.

Report last updated: 2012/10/03 00:00:00 GMT+0