Klinefelter syndrome and genetics

ALSO KNOWN AS: XXY syndrome

DEFINITION Klinefelter syndrome is a sex chromosome disorder in which males have an extra X chromosome. It is a relatively common genetic abnormality, accounting for ten out of every one thousand institutionalized intellectually disabled adults in industrialized nations, and is one of the more common chromosomal aberrations. The syndrome is named for Harry Klinefelter Jr., an American physician.

Risk Factors

Klinefelter syndrome only affects males. The syndrome results from a rare genetic event and is not affected by the actions of either parent.

Etiology and Genetics

The fundamental chromosomal defect associated with the syndrome is the presence of one or more extra X chromosomes. The normal human male karyotype (array of chromosomes) consists of twenty-two pairs of chromosomes, called autosomes, plus the XY pair, called sex chromosomes. The female also has twenty-two autosome pairs, but with an XX pair in place of the XY pair for the sex chromosomes. Klinefelter syndrome affects 1 in every 500 to 600 men. The incidence is relatively high in the intellectually disabled population.

Because individuals with Klinefelter syndrome have a Y chromosome, they are always male. Sometimes Klinefelter syndrome is the result of mosaicism, a condition in which an individual has two or more cell populations derived from the same fertilized ovum, with males having both normal (XY) karyotypes in some cells and abnormal karyotypes (usually with an extra X chromosome) in others. Individuals with sex chromosome complements of XXYY, XXXY, or XX can also be diagnosed with Klinefelter syndrome. Individuals with Klinefelter syndrome who have a sex chromosome complement of XX are male because although an entire Y chromosome is not present, a portion of a Y chromosome is often attached to another chromosome.

Symptoms

The classic type of Klinefelter syndrome usually becomes apparent at puberty, when the secondary sex characteristics develop. The testes fail to mature, causing primary hypogonadism, a condition resulting in smaller than normal testicles in males. In this classic type, degenerative testicular changes begin that eventually result in irreversible infertility. Gynecomastia, a condition characterized by abnormally large mammary glands in the male that sometimes secrete milk, is often present. This disorder is usually associated with learning disabilities, intellectual disabilities, and violent, antisocial behavior. Other common symptoms include abnormal body proportions (disproportionate height relative to arm span), chronic pulmonary disease, varicosities of the legs, and diabetes mellitus (which occurs in 8 percent of those afflicted with Klinefelter’s). Another 18 percent exhibit impaired glucose tolerance. Most people affected also have azoospermia (no spermatozoa in the semen) and low testosterone levels. However, men with the mosaic form of Klinefelter syndrome may be fertile.

Congenital hypogonadism appears as delayed puberty. Men with hypogonadism experience decreased libido, erection dysfunction, hot sweats, and depression. Genetic testing and careful physical examination may reveal Klinefelter syndrome to be the reason for the primary complaint of infertility. Intellectual disability is a frequent symptom of congenital chromosomal aberrations such as Klinefelter syndrome because of probable coincidental defective development of the central nervous system. Early spontaneous abortion is a common occurrence.

Screening and Diagnosis

A physical examination is one of the tests used to diagnose Klinefelter syndrome. This includes careful observation of the genital area and chest, as well as checking reflexes and mental functioning. The doctor may inquire about other medical conditions, family health history, growth, development, and sexual function. Blood or urine tests can detect abnormal hormone levels, which are a sign of the syndrome.

A type of chromosome test called karyotype analysis is the most accurate method for detecting Klinefelter syndrome and is needed to confirm a diagnosis of the condition. The test is usually performed by taking a blood sample that is examined for the shape and number of chromosomes.

Treatment and Therapy

Depending on the severity of the syndrome, treatment may include mastectomy to correct gynecomastia. Supplementation with testosterone may be necessary to induce the secondary sexual characteristics of puberty, although the testicular changes that lead to infertility cannot be prevented. Any intellectual disability present is irreversible. Psychotherapy with sexual counseling is appropriate when sexual dysfunction causes emotional problems. In people with the mosaic form of the syndrome who are fertile, genetic counseling is vital because they may pass on this chromosomal abnormality. Therapists should encourage discussion of feelings of confusion and rejection that commonly accompany this disorder, and they should attempt to reinforce the patient’s male identity. Hormonal therapy can provide some benefits, but both benefits and side effects of hormonal therapy should be made clear. Some men with Klinefelter syndrome are sociopathic; for this population, careful monitoring by probation officers or jail personnel can assist in identifying potential violent offenders, who can be offered psychological counseling.

Prevention and Outcomes

There is currently no cure for Klinefelter syndrome. However, most people who have the condition lead normal and productive lives.

Bibliography

Cody, Heather. “Klinefelter’s Syndrome.” Handbook of Neurodevelopmental and Genetic Disorders in Adults. Ed. Sam Goldstein and Cecil R. Reynolds. New York: Guilford, 2005. Print.

Goldstein, Sam, and Cecil R. Reynolds. Handbook of Neurodevelopmental and Genetic Disorders in Children. 2nd ed. New York: Guilford, 2011. Print.

Manning, M. A., and H. E. Hoyme. “Diagnosis and Management of the Adolescent Boy with Klinefelter Syndrome.” Adolescent Medicine 13.2 (2002): 367–74. Print.

Parekattil, Sijo J., and Ashok Agarwal. Male Infertility: Contemporary Clinical Approaches, Andrology, ART, and Antioxidants. New York: Springer, 2012. Print.

Parker, James N., and Phillip M. Parker, eds. The Official Parent’s Sourcebook on Klinefelter Syndrome: A Revised and Updated Directory for the Internet Age. San Diego: Icon Health, 2002. Print.

Probasco, Terri, and Gretchen A. Gibbs. Klinefelter Syndrome: Personal and Professional Guide. Richmond: Prinit, 1999. Print.

Simpson, Joe Leigh. “Klinefelter Syndrome.” Management of Genetic Syndromes. Ed. Suzanne B. Cassidy and Judith E. Allanson. 3rd ed. Hoboken: Wiley, 2010. Print.

Tarani, Luigi. “Life Span Development in Klinefelter Syndrome.” Life Span Development in Genetic Disorders: Behavioral and Neurobiological Aspects. Ed. Annapia Verri. New York: Nova Biomedical, 2008. Print.

United States. National Institutes of Health. Office of Research Reporting. Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families. By Robert Bock. Bethesda: National Inst. of Health, 1997. Print.

Van Rijn, Sophie, and Hanna Swaab. "Emotional Regulation in Adults with Klinefelter Syndrome (47,XXY): Neurocognitive Underpinnings and Associations with Mental Health Problems." Journal of Clinical Psychology, vol. 76, no. 1, 2020, pp. 228-238, doi: 10.1002/jclp.22871. Accessed 4 Sept. 2024.