Klinefelter syndrome(47,XXY)

By Egorov Peter

Klinefelter syndrome

• Individuals with

Klinefelter syndrome

have at least two X

chromosomes and at least

one Y chromosome.

(XXY)

47, XXY and XXY syndrome

(XXY)

Because of the extra chromosome, individuals with the condition are usually referred to as :

47,XXYXXYMales=

This chromosome constitution (karyotype) exists in roughly between 1:500 to 1:1000 live

male births

Cause The extra X chromosome is retained because of

a nondisjunction event during:

(XXY)

• Meiosis I (gametogenesis)

• Meiosis II in females

Meiosis I (gametogenesis)

• Nondisjunction occurs when homologous chromosomes (X and Y sex chromosomes) fail to separate, producing a sperm with an X and a Y chromosome.

• Fertilizing a normal (X) egg produces an XXY offspring.

• The XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in about 1 in 500 live male births.

(XXY)

Meiosis I (gametogenesis)

(XXY)

!!!

Meiosis II in females

• Another mechanism for retaining the extra X chromosome is through a nondisjunction event during meiosis II in the female.

• Nondisjunction will occur when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate.

• An XX egg is produced which, when fertilized with a Y sperm, yields XXY offspring.

(XXY)

Meiosis II in females

(XXY)

!!!

Signs and symptoms

Signs and symptoms of Klinefelter syndrome vary by age

(XXY)

Babies:

• Weak muscles

• Slow motor development — taking longer than average to sit up, crawl and walk

• Delay in speaking

• Quiet, docile personality

• Problems at birth, such as testicles that haven't descended into the scrotum

(XXY)

Signs and symptoms

Boys and teenagers:• Taller than average stature• Longer legs, shorter torso

and broader hips compared with other boys

• Absent, delayed or incomplete puberty

• After puberty, less muscular bodies and less facial and body hair compared with other teens

• Small, firm testicles• Small penis

(XXY)

• Enlarged breast tissue (gynecomastia)

• Weak bones• Low energy levels• Shyness• Difficulty expressing

feelings or socializing• Problems with reading,

writing, spelling or math• Attention problems

Signs and symptoms

Men:

• Weak bones

• Decreased facial and body hair

• Enlarged breast tissue

• Decreased sex drive or sexual problems

Signs and symptoms

• Infertility• Small testicles and penis• Taller than average stature

(XXY)

Variations

• 48,XXYY

• 48,XXXY

• The incidence of 49,XXXXY is 1 in 85,0000 to 100,000 male births

(XXY)

occur in 1 in 18,000–50,000 male births.

Mosaic or mosaicism

Mosaic or mosaicism donates the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg

Males with Klinefelter syndrome may have a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure.

Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. Thus far, only about 10 cases have been described in literature.

(XXY)

It is interesting

• Analogous XXY syndromes are known to occur in cats - specifically, the presence of calico(a spotted or parti-colored coat that is predominantly white, with patches of two other colors (often the two other colors are orange tabby and black )) or tortoiseshell markings in male cats is an indicator of the relevant abnormal karyotype.

• As such, male cats with calico or tortoiseshell markings are a model organism for Klinefelter syndrome.

(XXY)

http://en.wikipedia.org/wiki/File:Calico_cat_-_Phoebe.jpg

(XXY)

Percentages of Klinefelter's diagnosis divided by age groups, with most diagnoses occurring in adulthood

Diagnosing Klinefelter Syndrome

The greatest chances to make Klinefelter’s diagnosing are in following times of life:

Before or shortly after birth Early childhood Adolescence Adulthood.

For males in which Klinefelter syndrome is suspected, a special blood test is recommended to confirm the Klinefelter syndrome diagnosis.

(XXY)

Tests Blood test:

Blood test called a karyotype and is the standard diagnostic method Test looks at a person's chromosomes

Prenatal Testing:

many males have been diagnosed through amniocentesis or chorionic villus sampling (CVS)

• In amniocentesis, a sample of the fluid surrounding the fetus is withdrawn

• CVS is similar to amniocentesis. The procedure is done in the first trimester (during the fist three month of pregnancy, it’s important to establish a foundation of good health) and the fetal cells needed for examination are taken from the placenta

(XXY)

Amniocentesis procedure

Chorionic villus sampling (CVS)

• About 10% of Klinefelter cases are found by prenatal diagnosis.

• Only a quarter of the affected males are recognized as having Klinefelter syndrome at puberty (despite the presence of small testes )

• 25% received their diagnosis in late adulthood (about 64% affected individuals are not recognized as such)

• Often the diagnosis is made accidentally as a result of examinations and medical visits for reasons not linked to the condition

(XXY)

Some facts

Treatment

Testosterone treatment should begin at puberty:

can normalize body proportions and promote development of normal secondary sex characteristics

but does not treat infertility, gynecomastia and small testes

By 2010 over 100 successful pregnancies have been reported using IVF (In vitro fertilization) technology with surgically removed sperm material from men with Klinefelter syndrome

The results of a study on 87 Australian adults with the syndrome shows:

• Who have had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to those who had been diagnosed in adulthood

(XXY)

IVF (In vitro fertilization) Is a process by which an egg is fertilized by sperm outside the body: in

vitro

Involves:

• monitoring a woman's ovulatory process

• removing ovum or ova (egg or eggs) from the woman's ovaries

• letting sperm fertilize them in a fluid medium in a laboratory. When a woman's natural cycle is monitored to collect a naturally

selected ovum (egg) for fertilization (it is known as natural cycle IVF)

(XXY) A "naked" egg

the fertilized egg (zygote) is then transferred to the patient's uterus with the intention of establishing a successful pregnancy

Gynecomastia

Photo of male with severe asymmetrical gynecomastia, followed by a photo of the same male after a liposuction procedure.

Gross Pathology:

A large glandular mass of male breast tissue, surgically removed

Epidemiology • This syndrome, evenly spread in all ethnic groups, has a prevalence of

1-2 subjects every 1000 males in the general population

• 3.1 % of infertile males have Klinefelter syndrome

• The prevalence of the syndrome has increased over the past decades (according to a meta-analysis)

• However, this does not appear to be correlated with the increase of the age of the mother at conception

The results of a study on 87 Australian adults with the syndrome shows:

• Who have had a diagnosis and appropriate treatment from a very young age had a significant benefit with respect to those who had been diagnosed in adulthood

(XXY)

History of Klinefelter Syndrome

• It was first indentified in 1942. By the late 1950s, the cause of Klinefelter syndrome was discovered.

In 1942, Dr. Harry Klinefelter and his coworkers at the Massachusetts General Hospital in Boston published a report about 9 men who had enlarged breasts, sparse facial and body hair, small testes, and an inability to produce sperm.

By the late 1950s, researchers discovered that men with Klinefelter syndrome.

(XXY)

In the early 1970s • Researchers around the world sought to identify males having the

extra chromosome by screening large numbers of newborn babies.

• One of the largest of these studies checked the chromosomes of more than 40,000 infants.

The XXY chromosome arrangement appears to be one of the most common genetic abnormalities known (1 in 500 to 1 in 1,000 male births)

• Not a lot actually have Klinefelter syndrome symptoms. Many men live out their lives without ever suspecting that they have an additional chromosome.

(XXY)

Sources:• http://www.hindawi.com/journals/ije/2012/324835/

• http://en.wikipedia.org/wiki/Klinefelter_syndrome

• http://genetics.emedtv.com/klinefelter-syndrome/diagnosing-klinefelter-syndrome.html

• http://jama.jamanetwork.com/article.aspx?articleid=183701

• http://www.ncbi.nlm.nih.gov/

• http://www.researchgate.net/publication/20250975_Klinefelter's_syndrome_with_hypospadias_and_bilateral_cryptorchidism

• http://emedicine.medscape.com/article/945649-overview#showall

• http://www.patient.co.uk/health/klinefelters-syndrome

• http://www.yourhormones.info/endocrine_conditions/klinefelters_syndrome.aspx

• http://howshealth.com/klinefelter-syndrome/

• http://medical-dictionary.thefreedictionary.com/Klinefelter+syndrome