Kleinfelter's syndrome

HistoryKlinefeleters_karyotype.jpg
Klinefelter's syndrome was first discovered by Harry Klinefelter at the Massachusetts General Hospital in Boston. Him and his team published a report based on 9 male patient's symptoms ranging from enlarged breasts, sparse facial hair, small testes, to the inability to produce sperm. The disease was incorrectly attributed to an endocrine disorder.

During 1959, the perplexing sydrome affecting men was proven by Jacobs et al to be caused by an extra sex chromosome resulting in an XXY chromosomal arrangment.

During the 1970's a world wide effort was devised to accurately predict the frequency of the extra sex chomosome in male babies.

Symptoms
The manifestations of Klinefelter's symptoms can vary greatly from individual to individual and the intensity of symptoms can also vary greatly. Symptoms fall into three main categories: Physical symptoms, Language symptoms, and Social symptoms. Intensity of symptoms generally depends on the number of XXY cells present, the levels of testosterone production in the individual, and the age at the time of diagnosis.

Physical symptoms include a lack of muscle tone, less facial and body hair than normal, wide hips, and larger than average breasts. Children who are diagnosed with Klinefelter's will oftentimes have trouble with development of certain movements. For example, infants with Klinefelter's may learn to walk or crawl much later than other infants. During puberty, individuals with Klinefelter's will have reduced production of testosterone, which is what accounts for the changes in physical appearance. Teenagers with Klinefelter's may also be taller and leaner than other males of the same age. Males with Klinefelter's produce little or no sperm which usually results in infertility for the individual. Infertility is a common symptom, present in up to 95% of Klinefelter's cases. Individuals with Klinefelter's are also more susceptible to other physical disorders such as autoimmune disorders, breast cancer and osteoporosis.

Language impairments are also common amongst individuals with Klinefelter's Syndrome. These language impairments can include delayed onset of language development in early ages, problems reading and writing, problems talking, and the inability to express thoughts through the use of speech.

Social conditions associated with Klinefelter's involve trouble fitting in with peers and issues with school and sports. Infants and young children with Klinefelter's are oftentimes shy and reserved and may have trouble making friends. However social issues are generally overcome and most men with Klinefelter's will develop functioning social lives and normal social relationships later in life.

Detection
Detection of klinefelter’s syndrome depends on different diagnostic criteria and test results.

A diagnostic criterion is based on abnormal physical symptoms, such as large breasts in the male patient, small testes, and infertility. These alarming features would lead to a doctor’s suspicions and eventually a karyotype test. A karyotype test is a blood test that defines a person’s chromosomes using a peripheral blood sample. When the patient’s chromosomes are compared to a normal karotype, an extra x chromosome is observed resulting in a klinefelter’s diagnosis. This is the most common and most accurate method of testing for klinefelter's syndrome.

Diagnosis of klinefelter’s syndrome can also be achieved prenatally if a genetic disposition for the syndrome is suspected from a family history. Different prenatal tests include amniocentesis and chorionic villus sampling. Amniocentesis utilizes a sample of the fluid thats surrounds the fetus, the fluid sample contains fetal cells that can be examined for chromosomal abnormalities. If this method is preformed during the first trimester and the fetal cells are extracted from the placenta, the test is then referred to a chronic villus sampling (CVS).

Treatment and Medications
The XXY genetic variation is irreversible. Once diagnosed, Initial treatment involves measuring the amount of testosterone being produced since many males with Klinefelter's syndrome have low levels of testosterone. If testerone levels are found abnormally low then testosterone replacement therapy might be necessary. Testosterone replacement therapy uses a man-made form of testosterone, Dep-Testosterone. Dep-Testosterone is given on a regular basis every 13-14 days via intramuscular injections, skin patches, and gels.

Because males with Klinefelter's Syndrome often suffer from delayed cognitive development, other therapeutic methods may be used to benefit the patient during adolescence. Young males with Klinefelter's Syndrome usually suffer from language impairments, and speech therapy has shown to be helpful. Speech therapy is particularly important in helping the young male develop skills in understanding and producing more complex language.

Behavioral therapy might also be used to benefit the young male patient. Behavioral therapy is personalized from information obtained from a psychoeducational evaluation. The therapy is then adjusted to the patients strengths and weaknesses.

Treatment for infertility involve microsurgical techniques and artificial reproductive technologies (ART). Microsurgical testicular sperm extraction (TESE) is used to retrieve sperm directly from the testes to then be used for in-vitro fertilization (IVF) which injects a spermatozoon directly into an ovum.

Physical features like enlarged breasts in the males can be surgically reduced using cosmetic surgery. Surgery would achieve a physical apperance of normallcy,lessening social stigma and increasing the patients confidence.

Life Expectancy
Individuals with Klinefelter's are expected to live fairly normal lives and can live to be just as old as people without the disorder. Some treatments can also stimulate sexual development in individuals exhibiting signs of infertility. Generally most symptoms do not affect the quality of life of the individual and people with Klinefelter's can usually live their lives normally after development is completed. The only symptom that generally impacts the quality of life is infertility for individuals who wish to bear children. However, some treatments can help Klinefelter males deal with infertility and possibly stimulate fertility through further sexual development.

Inheritance
Klinefelter's Syndrome is not an inherited genetic disorder. Klinefelter's results from the development of an extra X chromosome during the development of the sexual cells that later form the individual. As a result Klinefelter's is a randomly occurring disorder and is not affected by inherited traits. Sex cells that develop an extra X chromosome develop this irregularity through nondisjunction.

Frequency
Klinefelter's is one of the most commonly chromosomally linked genetic disorders. The disorder can affect as many as 1 in 500 men. Individuals with Down Syndrome also generally exhibit symptoms of Klinefelter's syndrome and both disorders are more likely to occur during pregnancies of older women.