Kenneth Kee 2017 Smashwords Edition
by Kenneth Kee at Smashwords.com
book is dedicated
my wife Dorothy
book describes Klinefelter Syndrome, Diagnosis and Treatment and
Related Diseases which is seen in some of my patients in my Family
You Need to Treat Klinefelter Syndrome)
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I have been writing
medical articles for my blog http://kennethkee.blogspot.com
(A Simple Guide to Medical Condition) for the benefit of my patients
My purpose in writing
these simple guides was for the health education of my patients.
Health Education was
also my dissertation for my Ph.D (Healthcare Administration).
I then wrote an
autobiolographical account of his journey as a medical student to
family doctor on his other blog
account “A Family Doctor’s Tale” was combined with my early “A
Simple Guide to Medical Conditions” into a new Wordpress Blog “A
Family Doctor’s Tale” on http://kenkee481.wordpress.com.
From which many free
articles from the blog was taken and put together into 800 amazon
kindle books and 200 into Smashwords.com eBooks.
Some people have
complained that the simple guides are too simple.
For their information
they are made simple in order to educate the patients.
The later books go into
more details of medical conditions.
The first chapter is
always from my earlier blogs which unfortunately tends to have typos
and spelling mistakes.
Since 2013, I have
tried to improve my spelling and writing.
As I tried to bring you
the latest information about a condition or illness by reading the
latest journals both online and offline, I find that I am learning
more and improving on my own medical knowledge in diagnosis and
treatment for my patients.
Just by writing all
these simple guides I find that I have learned a lot from your
reviews (good or bad), criticism and advice.
I am sorry for the
repetitions in these simple guides as the second chapters onwards
have new information as compared to my first chapter taken from my
I also find repetition
definitely help me and maybe some readers to remember the facts in
the books more easily.
I apologize if these
repetitions are irritating to some readers.
What is Klinefelter
Klinefelter Syndrome is
an inherited disorder of the sex chromosome in which an extra X
chromosome is present (XXY)
Klinefelter syndrome is
a genetic disorder that happens in males with an extra X chromosome.
It happens in males and
is linked with hypo-gonads and infertility.
happens in about 1 out of 500 to 1,000 baby boys.
What is the Cause of
Normal people have 46
Chromosomes hold all of
the genes and DNA, the building blocks of the body.
The 2 sex chromosomes
(X and Y) decide if the baby becomes a boy or a girl.
Girls normally have 2 X
Boys normally have 1 X
and 1 Y chromosome.
occurs when a boy is born with at least 1 extra X chromosome.
Normally, this happens
due to 1 extra X chromosome.
This is recorded as
Women who get pregnant
after age 35 tend slightly more likely to have a boy with this
syndrome than younger women.
It is an inherited
disease produced by an extra X sex chromosome (XXY).
are XXXY and mosaicism (XY/XXY)
The testis formation is
involved leading to hypo-gonadism and low testosterone secretion.
What are the symptoms
of Klinefelter Syndrome?
Symptoms may be:
body appearances (long legs, short trunk, shoulder equal to hip size)
2. Abnormally large
breasts in boys (gynecomastia) in 50 per cent
4. Sexual problems -
Sexual desire and ability to have erections impaired
5. Penis is small
6. Testes are small,
insensitive and firmer than usual
7. Less than normal
amount of pubic, armpit, and facial hair
8. Tall height
9. Weaker muscles
10. Language learning
or reading impairment may be present
How do you made the
diagnosis of Klinefelter Syndrome?
may first be diagnosed when a man consults the doctor because of
Infertility is the most
Klinefelter Syndrome is often based on
1. Medical examination
2. Buccal smear for
cells to test for chromosones
(checking the chromosomes)
4. Semen count
Blood tests will be
done to check hormone levels such as:
5. Blood test for
6. Blood follicle
stimulating hormone (raised),
7. Blood luteinizing
hormones (raised or normal)
8. Blood estradiol, a
type of estrogen (raised)
gonadotropins are raised due to abnormal Leydig cell function.
What are the
complications of Klinefelter Syndrome?
The complications of
Klinefelter Syndrome are:
1. Teeth that are
enlarged and with a thinning surface is very frequent in Klinefelter
This is called
This can be seen on
also increases the risk of:
2. Attention deficient
disorders, such as lupus, rheumatoid arthritis, and Sjogren syndrome
4. Breast cancer in men
disabilities, including dyslexia, which affects reading
7. A rare type of tumor
called an extra-gonadal germ cell tumor
What is the treatment
of Klinefelter Syndrome?
Treatment should focus
on 3 major facets of the syndrome:
2. Gynecomastia, and
1. Male hormone
treatment (testosterone) can help:
a. Grow body hair
b. Improve appearance
d. Improve mood and
e. Increase energy and
f. Increase strength
In most cases
testosterone is started at puberty, around age 12 years, with the
dose raised over time, until it was adequate to maintain age-fitting
serum concentrations of testosterone, estradiol, follicle-stimulating
hormone (FSH), and luteinizing hormone (LH).
injections can also:
a. Increase strength
and facial hair growth;
b. Improve a more
muscular body type;
c. Raise sexual desire;
d. Enlarge the testes;
e. Improve mood,
self-image, and behavior; and
f. Protect against
does not treat infertility or gynecomastia.
Most men with this
syndrome are not able to get a woman pregnant.
But, an infertility
specialist may be able to help.
Seeing a doctor called
an endocrinologist may also be helpful.
2. Mastectomy surgery
may be done for Klinefelter patient with gynecomastia
3. Psychosocial therapy
is necessary together with hormonal treatment
A study suggested that
early hormonal therapy (EHT) can improve social behavior in boys with
The doctors of the
study believe that EHT helps to significantly minimize developmental
challenges and behavioral issues in 47,XXY boys.
4. Speech and
A team approach can
help in improving speech impairments, academic problems, and other
psychosocial and behavioral problems.
In children, early
speech and language therapy is very helpful for developing skills in
the knowledge and understanding of a more complicated language.
Boys with Klinefelter
syndrome should receive a complete psycho-educational evaluation
(IEP) to evaluate their learning strengths and weaknesses.
5. Physical and
Physical therapy is
advised for boys with hypo-tonia or delayed gross motor skills that
may involve muscle tone, balance, and coordination.
Occupational therapy is
advised in boys with motor dyspraxia (a developmental disorder of the
brain in childhood causing difficulty in activities requiring
coordination and movement).
What is the prognosis
of Klinefelter Syndrome?
In the past infertility
is present with Klinefelter syndrome.
However over 100
successful pregnancies have been reported using IVF technology with
surgically removed sperm material from men with Klinefelter syndrome
How is Klinefelter
Genetic counseling and
testing for Klinefelter Syndrome is useful to detect early cases.
Early hormone therapy
may improve the testosterone level in boys and help in their social
A report was published
in 1942 about men with a constellation of features:
5. Elevated urinary
The cause was thought
to be due to an unknown endocrine disorder until 1959 when
was found to be a chromosomal disorder in which there is an extra X
chromosome, leading to the karyotype 47,XXY
Today, the term
Klinefelter syndrome (KS) indicates a group of chromosomal disorders
in which the normal male karyotype, 46,XY, has at least one extra X
XXY aneuploidy, the
most frequent human sex chromosome disorder, has an incidence of 1 in
It is also the most
frequent chromosomal disorder linked with male hypo-gonadism and
Other sex chromosomal
aneuploidies are added in the KS group of chromosomal disorders.
Occurring less often,
48,XXYY and 48,XXXY happen in 1 per 17,000 to 50,000 male births,
while 49,XXXXY has a frequency of 1 per 85,000 to 100,000 male
Klinefelter syndrome is
(micro-orchidism or small testes, oligospermia and azoospermia),
2. Gynecomastia in late
3. Hyalinization and
fibrosis of the seminiferous tubules,
4. Raised urinary
gonadotropin levels, and
5. Behavioral concerns.
may be diagnosed pre-natally from fetal cytogenetic analyses done on
chorionic villi or amniocytes.
If Klinefelter syndrome
is not diagnosed pre-natally, a patient with 47,XXY karyotype may
show different subtle, age-related medical signs that would induce
testing consists of:
1. Karyotype analysis
on peripheral blood lymphocytes,
2. XCAT-KS buccal swab
3. Fluorescence in-situ
hybridization (FISH), and
Early recognition and
anticipatory treatment are particularly helpful in Klinefelter
Until 1996, men with
Klinefelter syndrome were regarded as infertile.
New developments in
microsurgical methods and advances in artificial reproductive
technologies (ART) have allowed over 50% of men with Klinefelter
syndrome to produce their own children
The X chromosome
carries genes that have a part in many organ systems, playing a part
in testes function, brain development, and growth
The results of an extra
X chromosome, normally obtained through a non-disjunctional error
during parental gameto-genesis, are hypo-gonadism, gynecomastia, and
psychosocial behavioral concerns.
The rise of more than
one extra X or Y chromosome to a normal male karyotype results in
different cognitive and physical abnormalities.
As the number of
supernumerary X chromosomes rises, somatic and cognitive development
tends more likely to be affected.
cardiovascular anomalies can become more severe.
Gonadal development is
mainly vulnerable to each extra X chromosome, leading to seminiferous
tubule dysgenesis and infertility, as well as hypo-plastic and
malformed genitalia, as observed in polysomy X males.
A type of primary
testicular failure happens in males with Klinefelter Syndrome, with
raised gonadotropin levels because of loss of feedback inhibition by
the pituitary gland.
Also, mental capacity
decreases with extra X chromosomes.
quotient (IQ) score is decreased by about 15 points for each
supernumerary X chromosome, but results about decreased mental
capacity must be shown cautiously.
All main areas of
development, such as expressive and receptive language and
coordination, are involved by extra X chromosome material.
1. Eunuchoid body
proportions or female allotment of adipose tissue
2. Sparse or absent
facial, axillary, pubic, or body hair
4. Reduced muscle mass
5. Reduced physical
6. Small testes and
7. Decreased libido
Lack of functional
seminiferous tubules and Sertoli cells, producing reduction of
inhibin B levels (the hormone regulator of the follicle-stimulating
hormone or FSH level)
hypothalamic-pituitary-gonadal axis in pubertal boys
Men with Klinefelter
syndrome have an increased danger of:
1. Autoimmune diseases,
2. Diabetes mellitus
and its linked complications,
3. Osteopenia and
4. Tumors (breast and
5. Systemic lupus
7. Sjogren syndrome
This increased danger
is comparable to the disease danger for 46,XX females.
results of a normal male with Klinefelter syndrome show:
1. Low to low-normal
2. High luteinizing
hormone (LH) and FSH levels, and, often,
3. Raised estradiol
The decrease of
testosterone production develops over the patient's life span but not
all male patients have hypo-gonadism
It is not clear if the
disorder linked with Klinefelter syndrome is a result of
hypo-gonadism and hyper-estrogenism or is because of abnormal
function of X chromosome–linked genes
In boys with
Klinefelter syndrome, the degree of phenotypic anomaly is related to
the danger for impaired quality of life (QOL).
analysis suggested that phenotype was responsible for 22% of the
variation in QOL among the boys in the study.
was thought to be produced by a supernumerary X chromosome in male.
The 47,XXY karyotype of
Klinefelter syndrome impulsively occurs when paired X chromosomes do
not succeed to separate (non-disjunction in stage I or II of meiosis,
during production of eggs or sperms).
Maternal and paternal
meiotic non-disjunction each is responsible for about 50% of
Klinefelter syndrome cases.
75% of maternal
non-disjunction cases are produced by meiosis I errors, which are
linked with higher maternal age.
Higher paternal age has
been linked to a possible higher risk of Klinefelter syndrome
non-disjunction accounts for mosaicism, which is observed in about
10% of Klinefelter syndrome patients.
Men with mosaicism are
less involved and are often not diagnosed
The androgen receptor
(AR) gene programs
the androgen receptor, which is sited on the X chromosome.
gene has a highly polymorphic trinucleotide (CAG) repeat sequence in
exon 1, and the length of this CAG repeat is inversely linked with
the functional response of the androgen receptor to androgens.
A short AR
CAG repeat progression links with a marked effect of androgens.
In patients having
Klinefelter syndrome, the X chromosome with the shortest AR
CAG repeat has been found to be specially not active; this method is
called skewed or non-random X-chromosome inactivation.
Patients with short AR
CAG recurrences have been observed to react better to androgen
therapy, to form more stable partnerships, and to obtain a higher
level of education compared with patients with long CAG recurrences.
Contrarily, long AR
CAG recurrence lengths are linked with:
1. Greater body height
and arm span,
2. Reduced bone
3. Reduced testicular