Information on the following diseases can be found in the Related Disorders section of this report:

• Klinefelter Syndrome
• Sotos Syndrome
• Marfan Syndrome
• Antisocial Personality Disorder

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. Major symptoms may include tall or very tall height (usually becoming apparent after the age of five or six, and severe cystic acne during adolescence.

Despite being tall, affected individuals are not particularly strong and often exhibit muscle weakness and poor coordination. Underdevelopment of the chest and shoulder muscles (pectoral and shoulder girdle musculature) is also common.

Children with XYY syndrome typically have normal intelligence, although, on average, IQ is 10 to 15 points lower than siblings. Affected children may exhibit mild delays in reaching developmental milestones. In approximately 50 percent of cases learning disabilities occur. Speech delays and language problems occur in some cases. 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, aggressive or defiant actions, or, in some cases, antisocial behavior. Other than being exceptionally tall and/or having behavioral problems, many affected individuals typically have a normal physical appearance (phenotype).

In some cases, physical characteristics of XYY syndrome may include an unusually long head with a slightly protrusive forehead (frontal bossing), long hands and feet, long ears, mild indentation in the lower area of the breastbone (pectus excavatum), and/or large teeth.

Occasionally, a bony formation across the joints in the two bones of the forearm resulting in stiffening of the affected joints (radio-ulnar synostosis) may occur. Additional rare or occasional findings include undescended testicles (cryptorchidism), an unusually small penis, or the urinary opening (meatus) located on the underside of the penis (hypospadias).
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The exact cause of XYY syndrome is not understood. XYY syndrome is a rare genetic 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. The reason of the presence of the extra Y chromosome is not known. In very rare instances, the syndrome has been passed from father to son; however, in the vast majority of cases, heredity cannot be established.
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XYY syndrome is a rare chromosomal disorder present at birth that affects only males. It is estimated to occur in approximately one out of 841 to 1000 live births.
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Symptoms of the following disorders can be similar to those of XYY syndrome. Comparisons may be useful for a differential diagnosis:

Klinefelter syndrome is characterized by the presence of one or more extra x-chromosomes. It affects only males. Individuals with this syndrome tend to be tall and slim in childhood. A striking lack of muscular development, and a small penis and testicles may also occur. Lower than average intelligence, language difficulties, intention tremor, and behavioral problems may be other symptoms. (For more information on this disorder, choose "Klinefelter" as your search term in the Rare Disease Database.)

Sotos syndrome is a rare genetic disorder characterized by excessive growth that occurs prior to and after birth (prenatally and postnatally). At birth, affected infants have unusually increased body length that is abnormal in proportion to weight, which may also be above average; in addition, newborns typically demonstrate advanced bone growth, abnormally large hands and/or feet, and characteristic facial features. Abnormally rapid growth continues after birth until approximately four or five years of age, at which time growth may slow to a normal rate. Adult height usually exceeds the 50th percentile. Some affected individuals may reach excessive adult heights; males of 193 cm to 203 cm (6 feet 4 inches to 6 feet 8 inches) and females up to 188 cm (6 feet 2 inches) have been described. Affected infants and children may also demonstrate developmental abnormalities including delays in reaching developmental milestones (e.g., sitting, crawling, walking); delays in the acquisition of skills requiring the coordination of muscular and mental activity (psychomotor retardation); delayed language skills; and mild to severe mental retardation. Characteristic facial abnormalities may include an unusually large head (macrocephaly) that may appear elongated (dolichocephalic) with an abnormally prominent forehead (frontal bossing); widely-spaced eyes (ocular hypertelorism); downwardly slanting eyelid folds (palpebral fissures); a highly-arched roof of the mouth (palate); protrusion of the lower jaw (prognathism); and/or a pointed chin. Most cases of Sotos syndrome occur randomly (sporadically), probably as a new genetic mutation. In rare cases, however, when a positive family history is found, the disorder may be inherited as an autosomal dominant genetic trait.
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Marfan syndrome is a rare inherited disorder of the connective tissues. People with Marfan Syndrome are unusually tall and thin. Both the face and the limbs are abnormally long. Other features may include excessive joint mobility, flat feet, muscle weakness (hypotonia), a protruding or indented breast bone (sternum) and curvature of the spine (scoliosis). The teeth may be crowded because of an abnormally high palate. Stretch marks (striae) may appear on the skin. Individuals with Marfan Syndrome may have significant cardiovascular problems. The most common of these is mitral valve prolapse, which is often without symptoms. Mitral valve prolapse is characterized by the incomplete closure of the heart valve and the backward flow of blood in the heart. Enlargement and degeneration of the aorta, aortic aneurysm (a bulge of the wall of the aorta), and aortic regurgitation (backward flow of blood) are also common. If left untreated, life-threatening complications may occur. About 50 percent of patients with Marfan Syndrome experience an abnormal displacement of the lens within the eyes (ectopia lentis). Another major symptom is nearsightedness (myopia). Other findings that relate to the eye may include an increased axial globe length, flatness of the cornea and occasionally retinal detachment. These conditions are diagnosed by a physician who specializes in eye diseases (ophthalmologist). Emphysema, which causes destructive changes and the loss of elasticity of the lungs, develops in almost all patients with Marfan Syndrome. A collapsed lung (pneumothorax) occurs in 5 percent of patients, either spontaneously or traumatically, and requires immediate attention. (For more information on this disorder, choose "Marfan" as your search term in the Rare Disease Database.)

Antisocial Personality Disorder is a mental illness characterized in early childhood by behavior such as lying, stealing, fighting, truancy and resisting authority. During adolescence, there may be excessive drinking, use of illicit drugs and aggressive sexual behavior. The behavioral difficulties usually last throughout adult life. In many cases disrespect for authority leads to problems with the law. (For more information on this disorder, choose "Antisocial Personality Disorder" as your search term in the Rare Disease Database.)
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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.

Treatment
Treatment of XYY syndrome is symptomatic and supportive. Counseling for behavioral or sexual problems may be of benefit. In most cases, affected individuals are very responsive to early intervention and treatment. Affected individuals should undergo clinical assessment of muscle tone and strength by six months of age. Speech and language assessment should occur during the first 24 months. Reading assessment should occur by school age to rule out dyslexia. Treatment of acne may help an affected individual’s self-image.
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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

The XXYY Project (www.xxyysyndrome.org) is conducting a research study to examine the similarities and unique aspects of all forms of sex chromosome abnormalities. It begins in July 2004 and will be conducted at the Children’s Hospital in Denver, Colorad, and the UC Davis MIND Institute in Sacramento. The study will last one year. Its purpose is to document and publish the medical and psychological differences between all sex chromosome anomalies. Limited transportation assistance may be available. There are no age requirements. For information, contact:

Renee Beauregard
Phone: (303) 400-3456
Toll Free: (888) 503-3456
E-mail: info@xxyysyndrome.org

TEXTBOOKS
Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:70.

Behrman RE., ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:535-6.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:61-2.

JOURNAL ARTICLES
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.

Robinson DO, Jacobs PA, The origin of the extra Y chromosome in males with a 47,XYY karyotype. Hum Mol Genet. 1999;8:2205-9.

Suzuki Y, et al., Bilateral cryptorchidism associated with 47,XYY karyotype. Int Urol Nephrol. 1999;31:709-13.

Abramsky L, Chapple J, 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counseling. Prenat Diagn. 1997;17:363-8. Comment In: Prenat Diagn. 1998;18:303-4.

Fryns JP, et al., XYY syndrome and other Y chromosome polysomies. Mental status and psychosocial functioning. Genet Couns. 1995;197-206.

Robinson A, et al., Prognosis of prenatally diagnosed children with sex chromosome aneuploidy. Am J Med Genet. 1992;44:365-8.

Nielsen J, Wohlert M, Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87:81-3.

Schiavi RC, et al., Sex chromosome anomalies, hormones, and sexuality. Arch Gen Psychiatry. 1988;45:19-24.

Benet J, Martin RH, Sperm chromosome complements in a 47,XYY man. Hum Genet. 1988;78:313-5.

Salbenblatt JA, et al., Gross and fine motor development in 47,XXY and 47,XYY males. Pediatrics. 1987;80:240-4.

Varrela J, Alvesalo L, Effects of the Y chromosome on quantitative growth: an anthropometric study of 47,XYY males. Am J Phys Anthropol. 1985;68:239-245.

Cohen FL, Durham JD, Sex chromosome variations in school-age children. J Sch Health. 1985;55:99-102.