Klinefelter Syndrome

Definition

Klinefelter syndrome is a chromosomal disorder that affects only males. People with this condition are born with at least one extra X chromosome. The syndrome was first identified and described in 1942 by Harry Fitch Klinefelter, Jr., an American physician.

Description

Klinefelter syndrome is a condition in which one or more extra X chromosomes are present in a male. Boys with this condition appear normal at birth. They enter puberty normally, but by mid puberty have low levels of testosterone causing small testicles and the inability to make sperm. Affected males may also have learning disabilities and behavior problems such as shyness and immaturity, and an increased risk for certain other health problems.

Klinefelter syndrome is one of the most common chromosomal abnormalities. About 1 in every 500 to 800 males is born with this disorder; approximately 3000 affected boys are born each year in the United States. About 3% of the infertile male population have Klinefelter syndrome. The condition appears to affect all racial and ethnic groups equally.

Causes and symptoms

Chromosomes are found in the cells in the body. Chromosomes contain genes, structures that tell the body how to grow and develop. Chromosomes are responsible for passing on hereditary traits from parents to child. Chromosomes also determine whether the child will be male or female. Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes are called X and Y. The combination of these two types of chromosomes determines the sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

In Klinefelter syndrome, a problem very early in development results in an abnormal number of chromosomes. About 60% of embryos with Klinefelter syndrome do not survive the fetal period. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Approximately 1/3 of all males with Klinefelter syndrome have other chromosomal abnormalities involving an extra X chromosome. Mosaic Klinefelter syndrome occurs when some of the cells in the body have an extra X chromosome and the others have normal male chromosomes. These males can have the same or milder symptoms than non-mosaic Klinefelter syndrome. Males with more than one additional extra X chromosome, such as 48,XXXY, are usually more severely affected than males with 47,XXY.

Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy is not increased above the general population risk.

The symptoms of Klinefelter syndrome are variable and not every affected person will have all of the features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs. Approximately 20-50% have a mild intention tremor, an uncontrolled shaking. Many males with Klinefelter syndrome have poor upper body strength and can be clumsy. Klinefelter syndrome does not cause homosexuality. Approximately 1/3 of males with Klinefelter syndrome have gynecomastia or breast growth, some requiring breast reduction surgery.

Most boys enter puberty normally, though some can be delayed. The Leydig cells in the testicles usually produce testosterone. With Klinefelter syndrome, the Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of normal. This can lead to decreased facial and pubic hair growth. The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Normally, FSH and LH help the immature sperm cells grow and develop. In Klinefelter syndrome, there are few or no sperm cells. The increased amount of FSH and LH causes hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules, where the sperm are normally located. As a result, the testicles appear smaller and firmer than normal. With rare exception, men with Klinefelter syndrome are infertile because they can not make sperm.

While it was once believed that all boys with Klinefelter syndrome are mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Approximately 50% of males with Klinefelter syndrome are dyslexic.

Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy, anxious, or immature than their peers. They can also have poor judgment and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with Klinefelter syndrome can also have anxiety, nervousness and/or depression.

The greater the number of X chromosomes present, the greater the disability; each extra X chromosome lowers the child's IQ by about 15 points. Boys with several extra X-chromosomes have distinctive facial features, more severe retardation, deformities of bony structures, and even more disordered development of male features.

Diagnosis

Diagnosis of Klinefelter syndrome is made by examining chromosomes for evidence of more than one X chromosome present in a male. This can be done in pregnancy with prenatal testing such as a chorionic villus sampling or amniocentesis. Chorionic villus sampling is a procedure done early in pregnancy (approximately 10-12 weeks) to obtain a small sample of the placenta for testing. An amniocentesis is done further along in pregnancy (from approximately 16-18 weeks) to obtain a sample of fluid surrounding the baby for testing. Both procedures have a risk of miscarriage. Usually these procedures are done for a reason other than diagnosing Klinefelter syndrome. For example, a prenatal diagnostic procedure may be done on an older woman to determine if her baby has Down syndrome. If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male, chromosome testing can also be on a small blood or skin sample after birth.

Many men with Klinefelter syndrome go through life without being diagnosed. The two most common complaints leading to diagnosis of the condition are gynecomastia and infertility.

Treatment

There is no treatment available as of the early 2000s to change a person's chromosomal makeup. Children with Klinefelter syndrome may benefit from speech therapy for speech problems or other educational interventions for learning disabilities. Testosterone injections started around the time of puberty may help to produce more normal development including more muscle mass, hair growth and increased sex drive. Testosterone supplementation will not increase testicular size, decrease breast growth or correct infertility. Psychiatric consultation may be helpful when the boy reaches adolescence.

Some doctors recommend mastectomy as a surgical treatment for gynecomastia, on the grounds that the enlarged breasts are often socially stressful for affected males and significantly increase their risk of breast cancer.

Prognosis

While many men with Klinefelter syndrome go on to live normal lives, nearly 100% of these men will be sterile (unable to produce a child). However, a few men with Klinefelter syndrome have been reported who have fathered a child through the use of assisted fertility services.

Males with Klinefelter syndrome have an increased risk of several systemic conditions, including epilepsy, osteoporosis, such autoimmune disorders as lupus and arthritis, diabetes, and breast and germ cell tumors. One Danish study reported in 2004 that men with Klinefelter's syndrome have a slightly shortened life span, dying about 2.1 years earlier than men without the syndrome.

KEY TERMS

Chromosome— A microscopic thread-like structure found within each cell of the body and consists of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the total number of chromosomes or their shape and size (structure) may lead to physical or mental abnormalities.

Gonadotrophin— Hormones that stimulate the ovary and testicles.

Gynecomastia— Excessive growth of breast tissue in males.

Leydig cells— Cells that make up the endocrine tissue of the testis and produce testosterone. They are named for Franz von Leydig (1821–1908), the German professor of anatomy who first identified them.

Testosterone— Hormone produced in the testicles that is involved in male secondary sex characteristics.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Chromosomal Abnormalities." Section 19, Chapter 261 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Infertility." Section 18, Chapter 245 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Probasco, Teri, and Gretchen A. Gibbs. Klinefelter Syndrome. Richmond, IN: Prinit Press, 1999.

PERIODICALS

Bojesen, A., S. Juul, N. Birkebaek, and C. H. Gravholt. "Increased Mortality in Klinefelter Syndrome." Journal of Clinical Endocrinology and Metabolism 89 (August 2004): 3830-3834.

Chen, Harold, MD. "Klinefelter Syndrome." eMedicine December 17, 2004. 〈http://emedicine.com/ped/topic1252.htm〉.

Diamond, M., and L. A. Watson. "Androgen Insensitivity Syndrome and Klinefelter's Syndrome: Sex and Gender Considerations." Child and Adolescent Psychiatric Clinics of North America 13 (July 2004): 623-640.

Grosso, S., M. A. Farnetani, R. M. Di Bartolo, et al. "Electroencephalographic and Epileptic Patterns in X Chromosome Anomalies." Journal of Clinical Neurophysiology 21 (July-August 2004): 249-253.

Lanfranco, F., A. Kamischke, M. Zitzmann, and E. Nieschlag. "Klinefelter's Syndrome." Lancet 364 (July 17, 2004): 273-283.

Tyler, C., and J. C. Edman. "Down Syndrome, Turner Syndrome, and Klinefelter Syndrome: Primary Care throughout the Life Span." Primary Care 31 (September 2004): 627-648.

ORGANIZATIONS

Klinefelter's Organization. PO Box 60, Orpington, BR68ZQ. UK. 〈http://hometown.aol.com/KSCUK/index.htm〉.

Klinefelter Syndrome and Associates, Inc. PO Box 119, Roseville, CA 95678-0119. (916) 773-2999 or (888) 999-9428. Fax: (916) 773-1449. [email protected]. 〈http://www.genetic.org/ks〉.

National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100. Fax: (203) 798-2291. 〈http://www.rarediseases.org〉.

OTHER

Klinefelter Syndrome Support Group Home Page. 〈http://klinefeltersyndrome.org/index.html〉.

Klinefelter syndrome

Definition

Klinefelter syndrome is a chromosome disorder in males that results in hypogonadism (small penis and small firm testicles). People with this condition are born with at least one extra X chromosome.

Description

Klinefelter syndrome is a condition where one or more extra X-chromosomes are present in a male. Boys with this condition appear normal at birth, but the defect becomes apparent in puberty when secondary sexual characteristics fail to develop, or develop later. By mid-puberty, boys with Klinefelter syndrome have low levels of testosterone, resulting in small testicles and the inability to make sperm. Affected males may also have learning disabilities and behavior problems such as shyness and immaturity and at an increased risk for certain other health problems such as pulmonary disease, varicose veins, breast cancer , extragonadal germ cell tumor (a rare tumor), and osteoporosis. Some mild cases may be undetected, with no abnormalities present except infertility.

Demographics

Klinefelter syndrome is one of the most common chromosomal abnormalities. About 1 in every 500 to 800 males is born with this disorder. Approximately 3% of the infertile male population have Klinefelter syndrome.

Causes and symptoms

Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes are called X and Y. The combination of these two types of chromosomes determines the sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

In Klinefelter syndrome, a problem very early in fetal development results in an abnormal number of chromosomes. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Approximately 1/3 of all males with Klinefelter syndrome have other chromosome changes involving an extra X chromosome. Mosaic Klinefelter syndrome occurs when some of the cells in the body have an extra X chromosome and the other have normal male chromosomes. These males can have the same or milder symptoms than those with non-mosaic Klinefelter syndrome. Males with more than one additional extra X chromosome, such as 48, XXXY, are usually more severely affected than males with 47,XXY.

Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy for a woman who had a son with Klinefelter syndrome is not increased above the risk of the general population.

The symptoms of Klinefelter syndrome are variable; not every affected person will have all of the features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs. Approximately 20–50% have a mild intention tremor, an uncontrolled shaking. Many males with Klinefelter syndrome have poor upper body strength and can be clumsy. Klinefelter syndrome does not cause homosexuality . Approximately 1/3 of males with Klinefelter syndrome have breast growth, some requiring breast reduction surgery.

Most boys enter puberty normally, though some can be delayed. The Leydig cells in the testicles usually produce testosterone. With Klinefelter syndrome, the Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of normal. This can lead to decreased facial and pubic hair growth. The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Normally, FSH and LH help the immature sperm cells grown and develop. In Klinefelter syndrome, there are few or no sperm cells. The increased amount of FSH and LH cause hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules, where the sperm are normally located. As a result, the testicles appear smaller and firmer than normal. With rare exception, men with Klinefelter syndrome are infertile because they can not make sperm.

While it was once believed that all boys with Klinefelter syndrome were mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Approximately 50% of males with Klinefelter syndrome are dyslexic. They may also have attention deficient hyperactivity disorder.

Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy, anxious, or immature than their peers. They can also have poor judgement and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with Klinefelter syndrome can also have anxiety , nervousness and/or depression.

Taurodontism, an enlargement of the pulp of the teeth with surface thinning, is very common in Klinefelter syndrome and can be diagnosed with dental x rays.

The greater the number of X chromosomes present, the greater the disability. Boys with several extra X chromosomes have distinctive facial features, more severe retardation, deformities of bony structures, and even more disordered development of male features.

When to call the doctor

Parents should call a doctor if their son fails to develop secondary sexual characteristics at puberty.

Diagnosis

During a physical examination, a doctor will look for a simian crease (a single crease in the palm). A rectal exam may show an enlarged prostate. A single testicle may be present in the scrotum, indicating a probable undescended testicle. A semen examination will show low sperm count, while other tests will show decreased serum testosterone levels, increased levels of serum luteining and serum follicle stimulating hormones and increased serum estradiol levels (a type of estrogen).

Diagnosis of Klinefelter syndrome is confirmed by examining chromosomes for evidence of more than one X chromosome present in a male. This can be done in pregnancy with prenatal testing such as chorionic villus sampling or amniocentesis . Chorionic villus sampling is a procedure done early in pregnancy (approximately 10–12 weeks) to obtain a small sample of the placenta for testing. An amniocentesis is done further along in pregnancy (from approximately 16–18 weeks) to obtain a sample of fluid surrounding the baby for testing. Both procedures have a risk of miscarriage. Usually these procedures are done for a reason other than diagnosing Klinefelter syndrome. For example, a prenatal diagnostic procedure may be done on an older woman to determine if her baby has Down syndrome . If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male, chromosome testing can also be on a small blood or skin sample after birth.

Treatment

There is no treatment available to change chromosomal makeup. Children with Klinefelter syndrome may benefit from a speech therapist for speech problems or other educational intervention for learning disabilities. Testosterone injections started around the time of puberty and continued for life may help to produce more normal development, including more muscle mass, hair growth and increased sex drive. Testosterone supplementation will not increase testicular size, decrease breast growth or correct infertility.

Prognosis

While many men with Klinefelter syndrome live normal lives, nearly 100 percent of these men will be sterile (unable to produce a child). However, a few men with Klinefelter syndrome have been reported who have fathered a child through the use of assisted fertility services. Males with Klinefelter syndrome have an increased risk of several conditions such as osteoporosis, pulmonary disease, varicose veins, autoimmune disorders such as lupus and arthritis, diabetes, breast cancer and extragonadal germ cell tumor (a rare tumor).

Prevention

Klinefelter syndrome usually is not inherited but occurs during fetal development, so there is no means of preventing the disease. However, one risk factor for this condition is the mother giving birth at an older age; therefore, genetic counseling and testing is recommended.

Parental concerns

Families may wish to seek counseling regarding the effects of the syndrome on relationships within the family . Many people respond with guilt, fear , or blame when a genetic disorder is diagnosed in the family, or they may overprotect the affected member. Support groups are often good sources of information about Klinefelter syndrome; they can offer helpful suggestions about living with it as well as emotional support.

KEY TERMS

Follicle-stimulating hormone (FSH) —A pituitary hormone that in females stimulates the ovary to mature egg capsules (follicles) and in males stimulates sperm production.

Luteinizing hormone —A hormone secreted by the pituitary gland that regulates the menstrual cycle and triggers ovulation in females. In males it stimulates the testes to produce testosterone.

Testosterone —Male hormone produced by the testes and (in small amounts) in the ovaries. Testosterone is responsible for some masculine secondary sex characteristics such as growth of body hair and deepening voice. It also is sometimes given as part of hormone replacement therapy to women whose ovaries have been removed.

Resources

BOOKS

Bock, R. Understanding Klinefelter's Syndrome: A Guide for XXY Males and Their Families. Bethesda, MD: National Institutes of Health,1993.

Icon Health Publications. Klinefelter's Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA:Icon Health Publications, 2004.

Icon Health Publications. The Official Parent's Sourcebook on Klinefelter Syndrome. San Diego, CA:Icon Health Publications, 2002.

Probasco, Teri, and Gretchen A. Gibbs. Klinefelter Syndrome. Richmond, IN: Prinit Press, 1999.

ORGANIZATIONS

American Association for Klinefelter Syndrome Information and Support. 2945 West Farwell Avenue, Chicago, IL 60645-2925. (773) 761-5298, (800) 466-5747. <http://www.aaksis.org>

Klinefelter's Organisation. 234 Turton Road, Bolton, BL2 3EE, United Kingdom. <http://www.klinefelter.org.uk/>

Klinefelter Syndrome and Associates, Inc. PO Box 119, Roseville, CA 95678-0119. (916) 773-2999 or (888) 999-9428. Fax: (916) 773-1449. <http://www.genetic.org/ks>.

WEB SITES

Klinefelter Syndrome Support Group Home Page. <http://klinefeltersyndrome.org/index.html>

Judith Sims, MS Carin Lea Beltz, MS

Klinefelter syndrome

Definition

Klinefelter syndrome is a chromosome disorder in males. People with this condition are born with at least one extra X chromosome.

Description

Klinefelter syndrome is a condition where one or more extra X-chromosomes are present in a male. Boys with this condition appear normal at birth. They enter puberty normally, but by mid-puberty have low levels of testosterone causing small testicles and the inability to make sperm. Affected males may also have learning disabilities and behavior problems such as shyness and immaturity and are at an increased risk for certain health problems.

Genetic profile

Chromosomes are found in the cells in the body. Chromosomes contain genes, structures that tell the body

how to grow and develop. Chromosomes are responsible for passing on hereditary traits from parents to child. Chromosomes also determine whether the child will be male or female. Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes are called X and Y. The combination of these two types of chromosomes determines the sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

In Klinefelter syndrome, a problem very early in development results in an abnormal number of chromosomes. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Approximately one-third of all males with Klinefelter syndrome have other chromosome changes involving an extra X chromosome. Mosaic Klinefelter syndrome occurs when some of the cells in the body have an extra X chromosome and the other have normal male chromosomes. These males can have the same or milder symptoms than non-mosaic Klinefelter syndrome. Males with more than one additional extra X chromosome, such as 48,XXXY, are usually more severely affected than males with 47,XXY.

Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy is not increased above the general population risk.

Demographics

Klinefelter syndrome is one of the most common chromosomal abnormalities . About one in every 500 to 800 males is born with this disorder. Approximately 3% of the infertile male population have Klinefelter syndrome.

Signs and symptoms

The symptoms of Klinefelter syndrome are variable and not every affected person will have all of the features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs. Approximately 20–50% have a mild intention tremor, an uncontrolled shaking. Many males with Klinefelter syndrome have poor upper body strength and can be clumsy. Klinefelter syndrome does not cause homosexuality. Approximately one-third of males with Klinefelter syndrome have breast growth, some requiring breast reduction surgery.

Most boys enter puberty normally, though some can be delayed. The Leydig cells in the testicles usually produce testosterone. With Klinefelter syndrome, the Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of normal. This can lead to decreased facial and pubic hair growth. The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Normally, FSH and LH help the immature sperm cells grow and develop. In Klinefelter syndrome, there are few or no sperm cells. The increased amount of FSH and LH cause hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules, where the sperm are normally located. As a result, the testicles appear smaller and firmer than normal. With rare exception, men with Klinefelter syndrome are infertile because they can not make sperm.

While it was once believed that all boys with Klinefelter syndrome were mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Approximately 50% of males with Klinefelter syndrome are dyslexic.

Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy, anxious, or immature than their peers. They can also have poor judgement and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with Klinefelter syndrome can also have anxiety, nervousness and/or depression .

The greater the number of X-chromosomes present, the greater the disability. Boys with several extra X-chromosomes have distinctive facial features, more severe retardation, deformities of bony structures, and even more disordered development of male features.

Diagnosis

Diagnosis of Klinefelter syndrome is made by examining chromosomes for evidence of more than one X chromosome present in a male. This can be done in pregnancy with prenatal testing such as a chorionic villus sampling or amniocentesis . Chorionic villus sampling is a procedure done early in pregnancy (approximately 10–12 weeks) to obtain a small sample of the placenta for testing. An amniocentesis is done further along in pregnancy (from approximately 16–18 weeks) to obtain a sample of fluid surrounding the baby for testing. Both procedures have a risk of miscarriage. Usually these procedures are done for a reason other than diagnosing Klinefelter syndrome. For example, a prenatal diagnostic procedure may be done on an older woman to determine if her baby has Down syndrome . If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male, chromosome testing can also be on a small blood or skin sample after birth.

Treatment and management

There is no treatment available to change chromosomal makeup. Children with Klinefelter syndrome may benefit from a speech therapist for speech problems or other educational intervention for learning disabilities. Testosterone injections started around the time of puberty may help to produce more normal development including more muscle mass, hair growth and increased sex drive. Testosterone supplementation will not increase testicular size, decrease breast growth or correct infertility.

Prognosis

While many men with Klinefelter syndrome go on to live normal lives, nearly 100% of these men will be sterile (unable to produce a child). However, a few men with Klinefelter syndrome have been reported who have fathered a child through the use of assisted fertility services. Males with Klinefelter syndrome have an increased risk of several conditions such as osteoporosis , autoimmune disorders such as lupus and arthritis, diabetes , and both breast and germ cell tumors.

Resources

BOOKS

Bock, R. Understanding Klinefelter's Syndrome: A Guide for XXY Males and Their Families. National Institutes of Health, USA, 1993.

Probasco, Teri, and Gretchen A. Gibbs. Klinefelter Syndrome. Richmond, IN: Prinit Press, 1999.

PERIODICALS

Smyth, Cynthia M., and W. J. Bremner. "Klinefelter Syndrome." Archives of Internal Medicine 158 (1998): 1309–1314.

Smyth, Cynthia M. "Diagnosis and Treatment of Klinefelter Syndrome." Hospital Practice (September 15, 1999): 111–120.

Staessen, C., et al. "Preimplantation Diagnosis for X and Y Normality in Embryos from Three Klinefelter Patients." Human Reproduction 11, no. 8. (1996): 1650–1653.

ORGANIZATIONS

American Association for Klinefelter Syndrome Information and Support (AAKSIS) 2945 W. Farwell Ave., Chicago, IL 60645-2925. (773) 761-5298 or (888) 466-5747. Fax: (773) 761-5298. <http://[email protected]>.

Klinefelter Syndrome and Associates, Inc. PO Box 119, Roseville, CA 95678-0119. (916) 773-2999 or (888) 999-9428. Fax: (916) 773-1449. [email protected]. <http://www.genetic.org/ks>.

Klinefelter's Organization. PO Box 60, Orpington, BR68ZQ. UK <http://hometown.aol.com/KSCUK/index.htm>.

WEBSITES

Klinefelter Syndrome Support Group Home Page. <http://klinefeltersyndrome.org/index.html>.

Carin Lea Beltz, MS

Klinefelter syndrome

Definition

Klinefelter syndrome is a chromosome disorder in males. People with this condition are born with at least one extra X chromosome.

Description

Klinefelter syndrome is a condition where one or more extra X-chromosomes are present in a male. Boys with this condition appear normal at birth. They enter puberty normally, but by mid-puberty have low levels of testosterone causing small testicles and the inability to make sperm. Affected males may also have learning disabilities and behavior problems such as shyness and immaturity and are at an increased risk for certain health problems.

Genetic profile

Chromosomes are found in the cells in the body. Chromosomes contain genes, structures that tell the body how to grow and develop. Chromosomes are responsible for passing on hereditary traits from parents to child. Chromosomes also determine whether the child will be male or female. Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes are called X and Y. The combination of these two types of chromosomes determines the sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

In Klinefelter syndrome, a problem very early in development results in an abnormal number of chromosomes. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Approximately one-third of all males with Kline-felter syndrome have other chromosome changes involving an extra X chromosome. Mosaic Klinefelter syndrome occurs when some of the cells in the body have an extra X chromosome and the other have normal male chromosomes. These males can have the same or milder symptoms than non-mosaic Klinefelter syndrome. Males with more than one additional extra X chromosome, such as 48,XXXY, are usually more severely affected than males with 47,XXY.

Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy is not increased above the general population risk.

Demographics

Klinefelter syndrome is one of the most common chromosomal abnormalities . About one in every 500 to 800 males is born with this disorder. Approximately 3% of the infertile male population have Klinefelter syndrome.

Signs and symptoms

The symptoms of Klinefelter syndrome are variable and not every affected person will have all of the features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs. Approximately 20–50% have a mild intention tremor, an uncontrolled shaking. Many males with Klinefelter syndrome have poor upper body strength and can be clumsy. Klinefelter syndrome does not cause homosexuality. Approximately one-third of males with Klinefelter syndrome have breast growth, some requiring breast reduction surgery.

Most boys enter puberty normally, though some can be delayed. The Leydig cells in the testicles usually produce testosterone. With Klinefelter syndrome, the Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of normal. This can lead to decreased facial and pubic hair growth. The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Normally, FSH and LH help the immature sperm cells grow and develop. In Klinefelter syndrome, there are few or no sperm cells. The increased amount of FSH and LH cause hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules where the sperm are normally located. As a result, the testicles appear smaller and firmer than normal. With rare exception, men with Klinefelter syndrome are infertile because they can not make sperm.

While it was once believed that all boys with Klinefelter syndrome were mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Approximately 50% of males with Klinefelter syndrome are dyslexic.

Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy, anxious, or immature than their peers. They can also have poor judgement and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with Klinefelter syndrome can also have anxiety, nervousness, and/or depression .

The greater the number of X-chromosomes present, the greater the disability. Boys with several extra X-chromosomes have distinctive facial features, more severe retardation, deformities of bony structures, and even more disordered development of male features.

Diagnosis

Diagnosis of Klinefelter syndrome is made by examining chromosomes for evidence of more than one X chromosome present in a male. This can be done in pregnancy with prenatal testing such as a chorionic villus sampling or amniocentesis . Chorionic villus sampling is a procedure done early in pregnancy (approximately 10–12 weeks) to obtain a small sample of the placenta for testing. An amniocentesis is done further along in pregnancy (from approximately 16–18 weeks) to obtain a sample of fluid surrounding the baby for testing. Both procedures have a risk of miscarriage. Usually these procedures are done for a reason other than diagnosing Klinefelter syndrome. For example, a prenatal diagnostic procedure may be done on an older woman to determine if her baby has Down syndrome . If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male, chromosome testing can also be on a small blood or skin sample after birth.

Treatment and management

There is no treatment available to change chromosomal makeup. Children with Klinefelter syndrome may benefit from a speech therapist for speech problems or other educational intervention for learning disabilities. Testosterone injections started around the time of puberty may help to produce more normal development including more muscle mass, hair growth, and increased sex drive. Testosterone supplementation will not increase testicular size, decrease breast growth, or correct infertility.

Prognosis

While many men with Klinefelter syndrome go on to live normal lives, nearly 100% of these men will be sterile (unable to produce a child). However, a few men with Klinefelter syndrome have been reported who have fathered a child through the use of assisted fertility services. Males with Klinefelter syndrome have an increased risk of several conditions such as osteoporosis , autoimmune disorders such as lupus and arthritis, diabetes, and both breast and germ cell tumors.

Resources

BOOKS

Bock, R. Understanding Klinefelter's Syndrome: A Guide forXXY Males and Their Families. National Institutes of Health, USA, 1993.

Probasco, Teri, and Gretchen A. Gibbs. Klinefelter Syndrome. Richmond, IN: Prinit Press, 1999.

PERIODICALS

Smyth, Cynthia M., and W.J. Bremner. "Klinefelter Syndrome." Archives of Internal Medicine 158 (1998): 1309–1314.

Smyth, Cynthia M. "Diagnosis and Treatment of Klinefelter Syndrome." Hospital Practice (September 15, 1999): 111–120

Staessen, C., et al. "Preimplantation Diagnosis for X and Y Normality in Embryos from Three Klinefelter Patients." Human Reproduction 11, no. 8. (1996): 1650–1653.

ORGANIZATIONS

American Association for Klinefelter Syndrome Information and Support (AAKSIS) 2945 W. Farwell Ave., Chicago, IL 60645-2925. (773) 761-5298 or (888) 466-5747. Fax: (773) 761-5298. <http://[email protected]>.

Klinefelter Syndrome and Associates, Inc. PO Box 119, Roseville, CA 95678-0119. (916) 773-2999 or (888) 999-9428. Fax: (916) 773-1449. [email protected]. <http://www.genetic.org/ks>.

Klinefelter's Organization. PO Box 60, Orpington, BR68ZQ. UK <http://hometown.aol.com/KSCUK/index.htm>.

WEBSITES

Klinefelter Syndrome Support Group Home Page. <http://klinefeltersyndrome.org/index.html>.

Carin Lea Beltz, M.S.

KLINEFELTER'S SYNDROME

Klinefelter's syndrome (genotype 47, XXY) is a chromosomal anomaly in which affected males have an extra X chromosome. It occurs in 1:1,000 to 1:2,000 newborn males and has been detected in .003 percent of spontaneous abortions. This condition generally arises from failure of chromosomes to separate properly during meiosis. Specifically, an egg cell bearing an additional X chromosome (or a sperm bearing both an X and a Y chromosome) unites with a normal sex cell. Approximately one-third of affected individuals show multiple Xs (48, XXXY or 49, XXXXY) or both normal and abnormal cell lines (46, XY/47, XXY).

Klinefelter's syndrome is generally not apparent until puberty, at which time secondary sexual development does not proceed. Clinical features include small testes, tall stature, breast development, reduced hormonal levels, and sterility. Mosaics, or individuals with mixed cell lines, may be fertile. Behavioral features include depressed verbal intelligence, reduced activity, increased stress, and feelings of reduced masculinity. Families may be advised to seek hormonal therapy and counseling for these children.

See also:BIRTH DEFECTS; DEVELOPMENTAL DISABILITIES; GENOTYPE

Bibliography

"Klinefelter Syndrome." In the On-line Medical Dictionary, 1995-1998. Available from http://www.graylab.ac.uk/omd/index.html; INTERNET.

Plomin, Robert, John DeFries, Gerald McClearn, and Peter Mc-Guffin. Behavioral Genetics, 4th edition. New York: Worth Publishers, 2001.

Nancy L.Segal