1.
Klinefelter
syndrome
(47,XXY)
By Egorov Peter

2.
Klinefelter syndrome
• Individuals
with
Klinefelter
syndrome
have at least
two X
chromosome
s and at least
one Y
chromosome.
(XXY)

3.
47, XXY and XXY syndrome
(XXY)
Because of the extra chromosome, individuals with
the condition are usually referred to as :
47,XXY
XXY
Males=
This chromosome constitution (karyotype)
exists in roughly between 1:500 to 1:1000 live
male births

4.
Cause
The extra X chromosome is retained because of
a nondisjunction event during:
(XXY)
• Meiosis I (gametogenesis)
• Meiosis II in females

5.
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)

6.
Meiosis I (gametogenesis)
(XXY)
!!!

7.
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)

8.
Meiosis II in females
(XXY)
!!!

9.
Signs and symptoms
Signs and symptoms of Klinefelter syndrome
vary by age
(XXY)

10.
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

11.
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

12.
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

13.
(XXY)

14.
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.

15.
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)

16.
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)

17.
(XXY)
Percentages of Klinefelter's diagnosis divided by age
groups, with most diagnoses occurring in adulthood

18.
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)

19.
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)

20.
Amniocentesis procedure

21.
Chorionic villus sampling (CVS)

22.
• 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

23.
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)

24.
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

25.
Gynecomastia
Photo of male with severe asymmetrical gynecomastia, followed by
a photo of the same male after a liposuction procedure.

26.
Gross Pathology:
A large glandular mass of male breast tissue, surgically removed

27.
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)

28.
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)

29.
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)

30.
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