Excerpt for Klinefelter Syndrome, A Simple Guide To The Condition, Diagnosis, Treatment And Related Conditions by , available in its entirety at Smashwords

Klinefelter Syndrome,





The Condition,




Related Conditions


Dr Kenneth Kee

M.B.,B.S. (Singapore)

Ph.D (Healthcare Administration)

Copyright Kenneth Kee 2017 Smashwords Edition

Published by Kenneth Kee at Smashwords.com


This book is dedicated

To my wife Dorothy

And my children

Carolyn, Grace

And Kelvin

This book describes Klinefelter Syndrome, Diagnosis and Treatment and Related Diseases which is seen in some of my patients in my Family Clinic.

(What You Need to Treat Klinefelter Syndrome)

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Thank you for respecting the hard work of this author.


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 since 2007.

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 http://afamilydoctorstale.blogspot.com.

This autobiolographical 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 blog.

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.

Chapter 1

Klinefelter Syndrome

What is Klinefelter Syndrome?

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.

Klinefelter syndrome happens in about 1 out of 500 to 1,000 baby boys.

What is the Cause of Klinefelter Syndrome?


Normal people have 46 chromosomes.

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 chromosomes.

Boys normally have 1 X and 1 Y chromosome.

Klinefelter syndrome 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 XXY.

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).

Different combinations 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:

1. Disproportionate body appearances (long legs, short trunk, shoulder equal to hip size)

2. Abnormally large breasts in boys (gynecomastia) in 50 per cent

3. Infertility

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?


Klinefelter syndrome may first be diagnosed when a man consults the doctor because of infertility.

Infertility is the most frequent symptom.

Diagnosis of Klinefelter Syndrome is often based on

1. Medical examination of appearance

2. Buccal smear for cells to test for chromosones

3. Karyotyping (checking the chromosomes)

4. Semen count

Blood tests will be done to check hormone levels such as:

5. Blood test for testosterone (low),

6. Blood follicle stimulating hormone (raised),

7. Blood luteinizing hormones (raised or normal)

8. Blood estradiol, a type of estrogen (raised)

9. Urinary 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 syndrome.

This is called taurodontism.

This can be seen on dental x-rays.

Klinefelter syndrome also increases the risk of:

2. Attention deficient hyperactivity disorder

3. Autoimmune disorders, such as lupus, rheumatoid arthritis, and Sjogren syndrome

4. Breast cancer in men

5. Depression

6. Learning 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:

1. Hypo-gonadism,

2. Gynecomastia, and

3. Psychosocial problems.

1. Male hormone treatment (testosterone) can help:

a. Grow body hair

b. Improve appearance of muscles

c. Improve concentration

d. Improve mood and self esteem

e. Increase energy and sex drive

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).

Regular testosterone 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 precocious osteoporosis.

Testosterone therapy 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 Klinefelter syndrome.

The doctors of the study believe that EHT helps to significantly minimize developmental challenges and behavioral issues in 47,XXY boys.

4. Speech and behavioral therapy

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 occupational therapy

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 Syndrome prevented?

Prevention is by:

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 behavior.

Chapter 2


A report was published in 1942 about men with a constellation of features:

1. Testicular dysgenesis,

2. Microorchidism,

3. Eunuchoidism,

4. Gynecomastia,

5. Elevated urinary gonadotropins, and

6. Azoospermia.

The cause was thought to be due to an unknown endocrine disorder until 1959 when

Klinefelter syndrome 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 chromosome.

XXY aneuploidy, the most frequent human sex chromosome disorder, has an incidence of 1 in 500 males.

It is also the most frequent chromosomal disorder linked with male hypo-gonadism and infertility.

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 births.

Klinefelter syndrome is featured by:

1. Hypo-gonadism (micro-orchidism or small testes, oligospermia and azoospermia),

2. Gynecomastia in late puberty,

3. Hyalinization and fibrosis of the seminiferous tubules,

4. Raised urinary gonadotropin levels, and

5. Behavioral concerns.

Klinefelter syndrome 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 diagnostic testing.

Postnatal diagnostic testing consists of:

1. Karyotype analysis on peripheral blood lymphocytes,

2. XCAT-KS buccal swab test,

3. Fluorescence in-situ hybridization (FISH), and

4. Micro-arrays

Early recognition and anticipatory treatment are particularly helpful in Klinefelter syndrome.

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.

Skeletal and 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.

The intelligence 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.

Androgen deficiency produces:

1. Eunuchoid body proportions or female allotment of adipose tissue

2. Sparse or absent facial, axillary, pubic, or body hair

3. Gynecomastia

4. Reduced muscle mass and strength

5. Reduced physical endurance

6. Small testes and penis

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)

Change in 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 osteoporosis,

4. Tumors (breast and germ cells),

5. Systemic lupus erythematosus,

6. Rheumatoid arthritis, and

7. Sjogren syndrome

This increased danger is comparable to the disease danger for 46,XX females.

Blood laboratory results of a normal male with Klinefelter syndrome show:

1. Low to low-normal testosterone levels,

2. High luteinizing hormone (LH) and FSH levels, and, often,

3. Raised estradiol levels.

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).

Linear regression analysis suggested that phenotype was responsible for 22% of the variation in QOL among the boys in the study.


Klinefelter syndrome 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

Post-fertilization 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.

The AR 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 density,

3. Reduced testicular volume, and

4. Gynecomastia.

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