07-08-2013 Faculty of medicine of Syrian Private University. Please LIKE my page! http://facebook.com/NawrasAlHalabi متلازمة كلاينفلتر وتقانات أطفال الأنابيب .كلية الطب البشري في الجامعة السورية الخاصة

1. Klinefelter’s Syndrome
Nawras Al Halabi
nawras@me.com

2. Syndrome definition
• In medicine and psychology, a syndrome is the
association of several clinically recognizable features,
signs (observed by someone other than the patient),
symptoms (reported by the patient), phenomena or
characteristics that often occur together, so that the
presence of one or more features alerts the healthcare
provider to the possible presence of the others.

3. What is Klinefelter’s syndrome?
• A genetic disorder in which there is at least one extra X
chromosome to a standard human male karyotype.
• Frequency: roughly between 1:500 to 1:1000 live male births
• 47,XXY is the most common sex chromosome aneuploidy in
males and the second most common condition caused by the
presence of extra chromosomes.
Other mammals also have the XXY syndrome, including mice.

4. History
• The syndrome was named after Harry F. Klinefelter.
• In 1942, worked with Fuller Albright at Massachusetts
General Hospital in Boston, Massachusetts and first
described it in the same year.
• Firstly described in 9 men: Infertility, gynecomastia,
hypogonadism, elevated FSH, atrophic testis.
• By the late 1950’s, researches discovered that these
men had an extra sex chromosome thus having the
pattern XXY
• Pervious name: Seminiferous tubule dysgenesis was
no longer used.

5. Etiology
• Meiotic nondisjunction of chromosome pairs during the
first or second division of gametogenesis
• Mitotic nondisjunction on the developing zygote
• It’s a random event during the formation of
reproductive cells

6. Possible nondisjunction events leading to Klinefelter’s Syndrome.

7. Variations
• Males with Klinefelter syndrome may have a mosaic
47,XXY/46,XY.
• 48,XXYY and 48,XXXY occur in 1 in 18,000–50,000 male
births.
• 49,XXXXY is 1 in 85,000 to 100,000 male births.
(Additional chromosomal material can contribute to cardiac,
neurological, orthopedic and other anomalies.)
• only about 10 cases have been described in literature of
mosaicism 47,XXY/46,XX with clinical features suggestive
of Klinefelter syndrome

8. Diagnosis
• About 10% of Klinefelter cases are found by prenatal
diagnosis.
• About 25% received their diagnosis in late adulthood.
• Often the diagnosis is made accidentally as a result of
examinations and medical visits for reasons not linked to the
condition.
• The standard diagnostic method is the analysis of the
chromosomes' karyotype on lymphocytes.
• To confirm mosaicism, it is also possible to analyze the
karyotype using dermal fibroblasts or testicular tissue.

9. 1% 10%
18%
20%21%
18%
12%
Percentages of Klinefelter's diagnosis divided by
age groups (most diagnoses occurring in
adulthood)
0-9 years
10-19 years
20-29 years
30-39 years
40-49 years
50-59 years
60-69 years

10. Signs and symptoms
• There are many variances within the XXY population,
just as within the 46,XY population. It is possible to
characterize XXY males with body types and physical
characteristics.
• The only reliable method of identification is karyotype
testing.

11. Lifestyle with KS patients
As a Baby, Child, and Teen:
• May sit up, crawl, and walk later than other
infants.
• Weaker muscles
• Reduced strength
• They tend to be taller than average as they grow
up
• They may have less muscle control and
coordination.
• Entering puberty, these males don’t make as
much testosterone.

12. Lifestyle with KS patients
Mental:
• Speech/language deficits, learning
disabilities/academic issues and/or behavioral issues.
• Tend to be quiet and undemanding.
• Delays in language acquisition and development:
Children with Klinefelter syndrome have the greatest
difficulty with expressive language, which is the ability
to put thoughts, ideas, and emotions into words.
• They can face problems during adolescence:
emotional and behavioural, and difficulties at school.
• Most of them can achieve full independence from
their families in adulthood witch can lead a normal,
healthy life.

13. Signs and symptoms
Adulthood:
• Tall body stature and increased lenght of extremities and
Narrow sholders
• Decreased facial and body hair (Produce much less testosterone)
• Increased FSH, LH and normal/decreased testosterone levels
• Gynecomastia (increase in breast tissue)
• Increase of fatty tissue especially in abdomen and pelvis
• Atrophic testicular volume: 2-3 ml
• Decreased IQ levels
• Osteoporosis
• Increased risk of breast cancer, autoimmune disorders,
hypothyroidism

14. A person with typical untreated
(surgery/hormones) Klinefelter
46,XY/47,XXY mosaic

16. Treatment
The genetic variation is irreversible, we treat the sings and
symptoms with:
• Cosmetic surgery gynecomastia (increase in breast tissue).
• Males with Klinefelter’s Syndrome can be given testosterone
therapy, If given around the age of puberty, it can help a boy
have normal body development.
• Planned and timed psychosocial support should be provided
for young men with Klinefelter syndrome to ameliorate
current poor psychosocial outcomes.
• IVF technologies to help father children.

17. Spermatogenesis
• Mosaic KS (46,XY/47,XXY) usually severe
oligozoospermic. Azoospermia can be present in some
mosaic KS patients.
• Men with non-mosaic KS usually azoospermic

18. KS Patients Fertility
• Micro TESE is a successful retrieval technique for patients
with KS
• The recovery rate can be change with age, the average rate is
%50-55
• After 35 years of age sperm recovery dramatically decrease
• The pregnancy rate was similar (45%) to karyotypically
normal NOA patients
• All babies have normal chromosome constraction
• PGD should be advise and discuss with the couples before
the ICSI treatment

19. Sperm Recovery
Testicular sperm extraction (TESE)

20. Sperm Recovery
Micro TESE

21. Sperm Recovery
TESA

22. Intra Cytoplasmic Sperm Injection
(ICSI)

23. Intra Cytoplasmic Sperm Injection
(ICSI)

25. Embryo Transfer

26. Pre-implantation Genetic Diagnosis
(PGD)

27. Pre-implantation Genetic Diagnosis
(PGD)

28. Pre-implantation Genetic Diagnosis
(PGD)

29. People living with klinefelter
Caroline Cossey (XXXY)
• Cossey was raised as a boy,
but changed lifestyle to live
as a girl.
• She became a famous
model.
• She underwent sex-
reassignment surgery.
• Cossey was a James Bond
girl in the movie “For Your
Eyes Only.”

30. People living with klinefelter
Lili Elbe
• Elbe allegedly had Klinefelter’s.
• She was one of the first identifiable
recipients of male to female sex
reassignment surgery.
• Elbe was a fashion model.
• She was transsexual and underwent
experimental surgeries, her first
surgery was orchiectomy (removal
of testicles).
• Elbe was written about in David
Ebershoff’s best seller, The Danish
Girl.

31. XXY Movie (2007)
• XXY is a 2007 Argentine-Spanish-
French drama film written and
directed by Lucía Puenzo. Starring
Ricardo Darín, Valeria Bertuccelli,
Inés Efron, and Martín Piroyansky,
the film tells the story of a 15-year-
old intersex person, the way her
family copes with her condition and
the ultimate decision that she must
eventually make as she finds her
gender identity.