This sheet seeks to provide not only more up-to-date
information about Klinefelter's syndrome (KS) but also to give some
background as to why people have KS and the reasons for their
infertility. The information has been obtained from a wide
variety of sources and this sheet aims to present it in a matter of
fact manner. Throughout this document the emphasis is on the
word may. The problems given in this document do not represent
everyone with KS. It states what problems may occur in some
individuals. Some may have one or two of the problems, others
several and yet others still have none except infertility.
Many men with KS live normal lives, oblivious to the fact that they
have KS. Of those who find out, it is often when they seek
help for infertility, which may be their only problem. Many
are able to do ordinary jobs, either as employees, self-employed or
even employers, in both the public and private sectors, whether or
not they also have other conditions that may impair them. Many
KS men also get married or live in other relationships. Many
KS males have medical problems that are probably unconnected with
having KS and this should be borne in mind when reading this
sheet.
Basic
Genetics
Klinefelter's
syndrome is named after Harry F. Klinefelter (cline-felter) who
first described the syndrome in the USA in 1942.[i]
It is a genetic disorder that
only affects boys and men. Normally a person, whether male or
female, has a total of 46 chromosomes in the nucleus, which is the
control centre of each cell. Chromosomes are the genetic material
that contain the code of life: Deoxyribonucleic acid, better known
as DNA. Of those 46 chromosomes, 44 are grouped in a total of
22 pairs and are called autosomes,
the name given to the non-sex determining chromosomes that determine
other characteristics. In addition there are normally two sex
chromosomes, females having two X chromosomes and males having one X
and one Y. Each chromosome is made up of genes, each of which has a
specific role to perform. The Y chromosome contains the male
determining gene. Of the 46 chromosomes, half come from the
mother and half from the father. A normal male would have 44
autosomes and the X and Y sex chromosomes, making a total of 46.
This is expressed as 46,XY and is known as that individual's
karyotype
(carry-o-type). In Klinefelter's syndrome however, due
to one of nature's accidents, when the male sperm fuses with the
female egg, the fetal cells have at least one extra X
chromosome. The most common number of chromosomes found in KS
is 47, that is 44 autosomes and 3 sex chromosomes giving a karyotype
of 47,XXY.
The extra X
chromosome can come from either a sperm or an egg, with a 50:50
chance. However as maternal age increases so does the risk of having
a boy with KS. The same risk does not however occur as men get
older. Because KS is not passed on but occurs by accident, it
is said to be congenital, which means that it is not inherited, that
is, it is not an hereditary disorder. This means that
the parents of a boy who has Klinefelter's syndrome need not be
anxious about having more children as the likelihood of having
another KS boy is minimal.
What is a Mosaic/Mosaicism ?
Some KS males have
what is known as mosaicism (mose-aia-sisem) which means that
some of the cells in their body are ordinary 46,XY whilst others
are, for example, 47,XXY. This example would be expressed as
46,XY/47,XXY. Some of these individuals, because of where the
normal 46,XY cells are located, are able to produce sperm and father
children, whereas the majority who are non-mosaic are sterile, that
is, they are unable to produce sperm and father
children.
Basic statistics
KS is
estimated to be found in 1 in 1000 (0.1%) [ii], [iii]of live male births, but other studies have
suggested that the figure may be as high as 1 in 700
(approximately 0.14%) [iv]
A
minority of KS males have a relatively low IQ below 80 [vi] (a measure of intelligence relative to the
rest of the population; the average is normally 100, give or take
15)
Delayed language development occurs in 50% of cases [vii], [viii]
Breast
development, known as gynæcomastia (guy-na-co-mastia) occurs in some cases, however during
adolescence it can be a temporary finding (usually 40% of boys) [ix]
Examples [x] of other KS karyotypes are: 48,XXXY, 46,XX
(male), 46,XxY,
46,XX/47,XXY
Boys with
KS
Boys
with KS have a normal male body shape and are thus referred to as
being phenotypically (fee-no-typically) male. They may experience learning
difficulties, especially with verbal or spoken skills, which may
require appropriate speech therapy. They may have difficulty
in concentrating for more than a few minutes on any single
topic. They may have problems in socialising with other
children of their own age group. Boys with KS may have
difficulties in specific areas of learning, especially those that
are based upon a facility with language. This affects their
ability to learn to read and spell, as well as their ability to
learn arithmetic skills. Remedial teaching (learning support)
may be beneficial for such children, and a Statement of Special
Educational Needs is often appropriate [xi].
At puberty, blood
testosterone levels are normal initially but may fail to rise into
the normal adult range from age 14 onwards. A boy's hips may
develop fatty deposits (although this can occur in non-KS males) so
that the boys assume more of a female pear shape (described as
eunuchoid) and they may develop breast enlargement, though
this is also a common finding in non-KS boys. If testosterone
is low, muscle development and beard growth may be reduced, and
sexual interest lowered. Before puberty a KS boy's testes have
a lower number of sperm producing cells (spermatogonia) than his
peers, but after puberty has begun fibrosis & hyalinization
(hialin-i-zation) of the seminiferous (semi-nif-er-ous) tubules
begins, a process which results in sterility. In simple terms
hyalinization means that the seminiferous tubules become filled with
a substance called hyalin which hardens & blocks the
tubules. Fibrosis means that the tissue or cells surrounding
the tubules (called connective tissue) shrink & become
permanently scarred or damaged.
During puberty a KS boy
may begin to have problems at school if he has to participate in
school sport. If physical differences are present, these can
attract the unpleasant attention of his classmates and can result in
teasing and social isolation. Before puberty it is desirable
to discuss this in confidence with his headteacher and those other
members of staff who need to know. Should gynæcomastia develop
to a degree where it causes unhappiness to the boy, testosterone
treatment and surgery should be considered and the implications
fully discussed and understood by an affected adolescent before any
final decision is taken. If surgery is chosen, it is important
to ensure that the surgeon who will be operating has some experience
in doing so, as poor surgery can create worse psychological problems
than existed prior to the operation.
Men with
KS
Men with KS are usually
sterile. They tend to have longer arms and legs and tend to be
taller than their peers. Lack of emotion, fatigue and apathy
are common [xii] and other problems such as an increased
tendency to develop psychiatric disorders, [xiii]
may occur as a result of the
syndrome.
General information -
introduction
A number of other
characteristics may be associated with Klinefelter's syndrome that
are dealt with briefly. In the past, too much attention may have
been paid to problems affecting one or two individuals who also
happened to have KS, which has led to suggestions of associations
between the syndrome and other diseases (however see below).
Follow-up investigations have not necessarily confirmed such
findings, demonstrating a need for both parents, affected
individuals and those professionals working with them to be open
minded and not take what they read or hear necessarily as
fact. Corroboration of research by other researchers is
desirable before any suggested association between KS and something
else is accepted. An additional problem often encountered is
inaccurate information published in some medical reference books
aimed at the general public. Authors have not always checked
their facts and this had led to unnecessary anxiety in
readers. Similar problems are beginning to appear with some
medical information on the internet, with opinion sometimes
presented as fact.
Illnesses, physical conditions and emotional / behavioural
aspects
Disorders of the body's
defence system with antibodies attacking the body itself, appear to
be more common in KS with a greater tendency to develop breathing
(ie respiratory) disorders such as asthma.
There seems to be a
higher risk of developing diseases affecting the veins:
hypostatic leg ulcers and thrombophlebitis
(throm-bo-flea-bite-is) seem to be more common. In
thrombophlebitis the wall of a vein can become inflamed and this can
lead to the liquid blood becoming solidified and causing a blood
clot that impedes the progress of the blood in the affected area
There appears to be a
higher risk of developing osteoporosis
(also known as brittle bone disease) in which the bones gradually weaken and
are more likely to break. Men with KS who only have moderately
low levels of natural testosterone may have normal bone density
whilst those with lower bone density seem to have an increased bone
turnover [xiv]. Treatment with testosterone (more
later) may prevent this from developing. However there is
evidence which suggests that only early testosterone treatment
prevents reduced bone density. Later treatment (after puberty)
seems to offer no benefits.[xv], [xvi]. Decreasing bone mass which can lead
to osteoporosis, can be automatically measured by a bone density
scanner. A new test has also been developed which analyses a
urine sample for the presence of a collagen breakdown product, which
indicates the development of osteoporosis [xvii].
It has been suggested
that diabetes mellitus is associated with Klinefelter's syndrome but
the connection may be linked with the greater tendency for KS men to
be overweight as this disorder can occur in such individuals.
As yet there is no sound evidence linking diabetes with KS.
There is a
slightly
higher risk of developing the following two types of cancer.
Male breast
cancer is more common in
KS than in the normal male population. Almost 1% of all breast
cancers are in men[xviii]. Breast cancer is 20 times more
common in KS than in non-KS males. This means that roughly 3%
of KS men will develop breast cancer [xix]. Whilst this poses a risk, it needs
to be looked at in the context that it is estimated that 1 in 12
(around 9% of) women will develop breast cancer over their lifetime.
[xx]
That is, they have three times
the risk KS men have. The reported average age the cancer
starts is later than that found in women who develop breast cancer
[xxi]. Circumstantial evidence suggests a
link with gynæcomastia [xxii]
but this is open to question [xxiii]. Removal of the breasts may not
eliminate the risk as it has been suggested that the cause of the
cancer may be linked to the hormonal imbalances in KS, causing cells
to become cancerous [xxiv]. In women, a longer than normal
menopause can increase the risk because of fluctuating ostrogen
levels, [xxv] and this may have its equivalent in KS men.
Germ cell
cancers are those which
originate in the sperm producing cells. Whilst most of these
cells are situated in the testes, a few are in the body cavity below
the lungs where organs such as the liver are situated, called the
mediastinum. In KS there is a very small risk of developing germ cell cancer originating
in the mediastinum, a risk that is greatly reduced after the age of
thirty years. The peak risk group are aged between 15 and 30 years
old.[xxvi]
Physical impairments
There is a
condition, thought to be common in KS called taurodontism
(toro-dont-ism), which literally means "bull teeth". In
this condition the dental pulp - the living part of the tooth which
contains a nerve, occupies a greater area than normal. This
results in a thinner layer of the hard enamel which leads to an
increased risk of tooth decay [xxvii].
There is another condition, very
rare in KS, called radial ulnar synostosis in which the
radius and ulnar bones in the forearm are fused together. This
prevents rotation of the forearm.
Emotional and
behavioural aspects
There are a number of
emotional and behavioural problems associated with KS such as
shyness, difficulties in forming relationships, a lack of visible
facial emotion and of motivation. Low self-esteem may be an
issue for adolescents. Little is yet understood about the
reasons for these difficulties; some may be directly related to the
chromosomal abnormality and its influence on brain
development. Others are secondary to hormonal changes, and
their effect on physical development and maturation [xxviii].
Biology of male reproductive organs & testosterone
Testosterone
(test-os-ter-own) is a natural chemical which is produced by the
body and in males mostly comes from the testes (singular: testis),
the male sex organs. It is what is known as an androgen
(and-row-jen), one of a number of hormones responsible for
activating both the growing male sex organs and at puberty, beard
growth and voice deepening, for example. It is mainly produced
in the testes (95%) by the Leydig cells which are situated around
the seminiferous tubules (see below) in response to the reception of
luteinizing (loot-en-i-zing) hormone (or LH for short) produced by a
part of the brain called the anterior pituitary gland. Each
testis is divided into a series of chambers called lobules, each of
which contains coiled seminiferous tubules. Within these
tubules are two types of cell: the spermatogenic cells which develop
into sperm by a process called spermatogenesis, of which more later;
and the Sertoli cells, which nourish the maturing sperm
cells. The Sertoli cells also perform a number of other
functions which include releasing a hormone called Inhibin, which
controls the release from the Pituitary gland, of Follicle
Stimulating Hormone (or FSH). The seminiferous tubules
are surrounded by blood capillaries and groups of Leydig cells,
which release androgens, or sex hormones, one of which is
testosterone. Most of the remaining testosterone is produced
in the adrenal cortex, which is situated on the upper surface of
each kidney.
Spermatogenesis is the
name given to the process that occurs in the seminiferous tubules,
which produces sperm. This process goes on all the time from
the onset of puberty, in fertile males. Sperm producing cells
upon exposure to testosterone, divide to produce two "daughter"
cells, as they are called (although this in no way implies any
gender). These "daughter" cells contain the full set of 23
pairs of chromosomes (total = 46 chromosomes). One of these
"daughter" cells is a new sperm producing cell, whilst the other
cell further divides to form two new cells, each with only one
member of each chromosome pair. As the unfertilised egg also
contains only one member of each chromosome pair, the act of
fertilisation re-institutes an embryo with 46 chromosomes.
Now I shall discuss the
male hormone testosterone, which is known as an anabolic steroid as
one of its effects is to promote muscle growth. It should not
be confused with the drugs abused by some athletes and bodybuilders.
Testosterone is usually
given orally (in the form of tablets, by mouth), intramuscular
injections (into the muscle), implantation of pellets or in the form
of a transdermal (ie skin) patch. Testosterone is given in
the form of one or more of its compounds, that is basic testosterone
in a different form which affects how the body deals with it.
These compounds are known as esters and some are utilised by the
body more quickly than others. Testosterone preparations such
as Sustanon* contain a relatively fast acting and a slow
acting form, which are designed so that the drug can begin to work
within hours of injection, lasting from a few days (eg.
Testosterone propionate), to a few weeks (eg. Testosterone
enanthate).
One of the problems with
testosterone given by mouth is that it has to be given in relatively
high doses to have an effect as the liver, the organ which removes
poisonous substances from the blood, also inactivates testosterone.
Testosterone undecanoate (Restandol*) is given by
tablets. Each tablet lasts for between 2 to 6 hours normally
requiring between 2 and 4 tablets, taken at intervals, a day.
It is more effective if each tablet is taken with food, as this
reduces the amount destroyed by the liver. Men often find
tablet treatment is not strong enough to restore libido. *
note: these are the brand names for these medicines in the
United Kingdom. They may be known by different names
elsewhere.
The implantation of
testosterone pellets is another method, ideally being inserted in
the wall of the abdomen under local anæsthetic. An implant
containing 600mg to 1200mg of testosterone can last for between 4
and 6 months or more and it has been suggested that this is the best
form (in 1990) in which it can be given [xxix]. The main problem with implants is
their tendency to come out and need reinsertion. However a new
method of having testosterone became available in the UK in 1996,
called Andropatch*, which as a transdermal patch delivers testosterone through
the skin and one or more patches is worn every day.
Of all these products,
Sustanon
is the cheapest, followed by Restandol
which is quite expensive whilst the Andropatch appears to be the most expensive of these
three common forms of testosterone. This should not be a problem
however if you use the UK's National Health Service. The
following price comparisons (at 1998 prices [xxx]) should give you an idea of the relative
prices of these three commonly prescribed forms of testosterone.
Andropatch (transdermal) costs £48.00 for either a box
of 60 x 2.5mg, or a box of 30 x 5.0mg patches
Restandol(tablet) costs £8.69 for 28, or £17.38
for 56 tablets
Sustanon (injection) costs £3.67 for 3 x 1ml ampoules
of Sustanon 100, or £8.60 for 3 x 1ml ampoules of
Sustanon 250
Do I
need testosterone treatment ?
Not necessarily.
As mentioned earlier, testosterone offers the possibility of
preventing the development of fatty deposits round the hips &
breast development, where these occur. It can ensure normal
development of the penis if administered under the guidance of a
doctor [xxxi]
In adults it may reduce fatigue
etc., prevent osteoporosis [xxxii]
and help ensure satisfactory
sexual activity. However it should only continue to be taken
if you and your doctor feel it has benefited you. The amount
of testosterone produced in the testes by adult KS males varies
between individuals. You may find that you may need
testosterone treatment, but it may also offer no real benefit and
you may even experience unwanted side effects (see below) [xxxiii]. The dose needed will vary between
individuals and should be adjusted accordingly.
What type of
testosterone form should I ask my doctor for ?
Different forms (also
called esters) of testosterone can have different effects on
different individuals. One form may suit one person whilst
causing problems or having little effect on another. The type
chosen may be influenced by your preference as to how it should be
administered. You may find an injection into your muscle (an
intramuscular injection) more convenient, or you may prefer to have
tablets (oral administration) or a (transdermal) skin patch, for
example. Certain combinations of testosterone esters in a
product may prove less satisfactory and even undesirable. What
you should be aiming at is a product that gives a more or less
steady level of serum (a component of blood) testosterone.
Possible dangers from
prolonged use of testosterone
Unlike naturally
occurring testosterone, that introduced into the body as a result of
testosterone treatment can cause some long term problems [xxxiv]. Heart problems, hypertension and
the build-up of fluid in the body (ie: odema) can occur as a result
of salt and water retention by the body. There may be an
increased risk of atherosclerosis (are-thur-o-scler-o-sis) in which
the walls of the arteries narrow as the result of a build up of fat,
which increases the risk of a stroke. There is also evidence
of polycythemia (poly-sigh-theme-e-a) in which there is a higher
concentration of red blood cells in the blood than normal, though
the evidence suggests the link is with older men [xxxv]. In some men there is a risk that
too high a dose of testosterone (including in the short term) could
result in aggression, psychosis (sigh-co-sis) and mania [xxxvi]. There is a slight risk that
testosterone might cause problems for someone undergoing
anti-coagulant treatment. There may also be a risk of liver
damage.
Is there a link between KS and criminality
?
The simple answer to
this question is no. One problem is that KS is sometimes confused with a
different condition known as XYY
syndrome. Some early research in the 1960s suggested a link
between the possession of an extra Y chromosome (as in
XYY
syndrome) and aggression.[xxxvii]
While some research has shown a
higher number of XYY men had been found in high security prisons and
special hospitals, other studies do not support this view.
Later research found little evidence linking XYY syndrome with criminality.[xxxviii]
Whilst early research suggested
a link between criminality and KS, such as that by Nielsen[xxxix]
who found that 38% of KS
compared to 6% of XY males committed crimes, later research has not supported
this.[xl] It is also necessary to remember that KS
males are often less mature, passive, impressionable and more
dependent on others, often having few or no friends, and are
therefore more vulnerable to group pressure.[xli] Current thinking accepts that any
association is controversial[xlii]
and more research would be
needed before any firm conclusions could be drawn.
References
The KO aims to produce
information sheets containing more information about certain topics
mentioned in this information sheet, such as male breast cancer and
osteoporosis. These information sheets will be available free
to members of the KO.
All internet addresses
(URLs) given in this document were correct when this document was
issued in July 1998.
[i] original
paper: Klinefelter, H.F. et al: Syndrome Characterized
by Gynecomastia, Aspermatogenesis without A-Leydigism, &
increased Excretion of Follicle Stimulating Hormone; J.of
Clinical Endocrinology, 1942 (2) no.11: 615-627
[ii] Bock, R:
Understanding Kl
inefelter's Syndrome: A Guide for XXY males & their
families; National
Institutes of Health, USA, 1993 (NIH Pub.no: 93-3202) also available
at:
http://www.iacnet.com/health/15097321.htm
[iii] Sørensen, K: Klinefelter's Syndrome in Childhood,
Adolescence & Youth: A genetic, clinical, developmental,
psychiatric & psychological study; Parthenon, 1987
[iv] Ratcliffe, S.G et
al: Edinburgh Study
of Growth & Development of Children with Sex Chromosome
Abnormalities III (in: Children with Sex Chromosome Aneuploidy: Follow-up
studies), March of Dimes Birth Defects Foundation: Original Article
Series, 1986; 22(3):73-118 (eds. Ratcliffe, S.G & N.
Paul)
[ix] Ratcliffe, S.G et
al: Edinburgh Study
of Growth & Development of Children with Sex Chromosome
Abnormalities IV (in: Children & Young Adults with Sex Chromosome
Aneuploidy: Follow-up Clinical & Molecular studies), March of
Dimes Birth Defects Foundation: Original Article Series, 1991;
26(4):1-44 (eds. Evans, J.A et al)
[x] personal
communication with Professor
M.A.Ferguson-Smith
[xi] information supplied by Professor David
Skuse
[xiii] Martinus, J: Psychiatric Aspects of Klinefelter's
Syndrome in Adolescence; from Klinefelter's Syndrome eds. Bandmann, H.-J &
R.Breit, Springer, 1984
[xiv] Luisetto G. et al: Bone mass and mineral metabolism in
Klinefelter's syndrome; Osteoporos Int 1995;5(6):455-461
[xv] Kubler A. et al: The influence of testosterone
substitution on bone mineral density in patients with Klinefelter's
syndrome; Exp Clin
Endocrinol 1992;100(3):129-132
[xvi] This is supported by research by Wong, F.H.
et al: Loss of bone
mass in patients with Klinefelter's syndrome despite sufficient
testosterone replacement; Osteoporosis Int 1993, Jan; 3(1): 3-7
[xvii]OsteosalT is used with the electronic reader
InstaQuantT developed by Cortecs Diagnostics Limited, who can be
contacted either by E-mail at: [email protected] or by post
at: Newtech Square, Deeside Industrial Park, Deeside,
CH5 2NT, United Kingdom.
[xviii] Sasco, Annie J. et al: Review article: Epidemiology of male
breast cancer. A meta-analysis of published case-controlled studies
& discussion of selected ætiological
factors;
Int.J.Cancer, 1993 (53): 538-549; see also: Genetics of breast & ovarian
cancer
(Male breast
cancer); British
Medical Bulletin (50) no.3: 668; also personal communication with
Professor H.S.Jacobs (UCL Medical School) (1996)
[xix] research by Hultborn et al in 1997 suggests the risk of male breast
cancer in KS males may be as high as 7.5%, though it has been
acknowledged that methodological differences may account for that
figure. see:
Hultborn, R. et al: Prevalence of Klinefelter's syndrome in male breast cancer
patients; Anticancer
Res, Vol 17, Nov.1997: 4293-4297
[xx] Whitehouse, David & Maurice Slevin:
Cancer: the
facts; OUP, 1996
(2nd edition)
[xxi] Scheike, O et al: Male breast cancer; Acta Pathol Microbiol Scand, 1975 Suppl
251: 3-35 found an average age of 65.2 years out of 257 cases,
whereas Hultborn et al (see reference above) found the average age
to be 72 out of 93 cases
[xxiii] van Geel, A.N et al: A retrospective study of male breast
cancer in Holland;
Br J Surgery, 1985 Sept; 72(9): 724-727
[xxiv] Thomas, David B: Breast cancer in
men; Epidemiological
Reviews, 1993 (15) no.1: 220-231; for more information on male
breast cancer see:
http://interact.withus.com/interact/mbc/index.html; see
also: Volm, M.D. et al: Pituitary adenoma and bilateral male breast cancer: an
unusual association;
J.Surg.Oncol: Jan.1997, 64(1): 74-78
[xxvi]
? Hasle, H et al:
Cancer incidence in
men with Klinefelter syndrome; Br.J.Cancer 1995 Feb; 71(2): 416-420; ,
Hasle, H et al: Mediastinal germ cell tumour associated with Klinefelter
syndrome. A report of case and review of the
literature;
Eur.J.Pediatr. 1992 Oct; 151(10): 735-739; f Nichols, C.R et
al: Klinefelter's
syndrome associated with mediastinal germ cell
neoplasms; J.
Clinical Oncology 1987; 5(8): 1290-1294; For more information on
germ cell tumours generally, see:
http://www.mc.vanderbilt.edu/peds/pidl/hemeonc/germcell.html
note: Approximately 20% of
non-seminomatous malignant germ cell tumours are associated with
Klinefelter's syndrome (47,XXY). At least 8% of primary mediastinal
germ cell tumours are in men with KS.
[xxvii] Paulsen, C.Alvin & S.R.Plymate:
Klinefelter's
syndrome; from The
Genetic Basis of Common Diseases, eds. King, et al (Oxford
Monographs on Medical Genetics, 1992) chapter 44
[xxxiv] Gooren, Louis J.G. & Kaas H. Polderman:
Safety aspects of
androgen therapy;
in 'Testosterone: action, deficiency, substitution' eds.
E. Nieschlag & H.M.Behre, Springer, 1990
[xxxv] Hajjar, R.R. et al: Outcomes of long-term testosterone
replacement in older hypogonadal males: a retrospective
analysis;
J.Clin.Endocrinol.Metab, Vol 82, Nov.1997: 3793-3796; Drinka,
P.J. et al: Polycythemia as a complication of testosterone replacement
therapy in nursing home men with low testosterone
levels;
J.Am.Geriatr.Soc, Vol 43, Aug.1995: 899-901
[xxxvi] there may be an association between KS and
bipolar disorder: see:
Everman, D.B. & Stoudemire, A: Bipolar disorder associated with
Klinefelter's syndrome and other chromosomal
abnormalities;
Psychosomatics, Vol 35, Jan.1994: 35-40; Bekaroglu, M. et al:
Bipolar affective
disorder associated with Klinefelter's syndrome - a case
report;
Isr.J.Psychiatry Relat.Sci., Vol 34(4) 1997:
308-310
[xxxvii] Wilson, J.Q. & Herrnstein, R.J:
Crime and Human
Nature; Touchstone,
1986
[xxxviii] Owen, R.D: The 47,XYY male: a
review;
Psychological Bulletin, Vol 78, 1972: 209-233; Thielgaard, R:
Aggression and XYY
personality;
Int.J.of Law and Psychiatry, Vol 6, 1983: 413-421
[xxxix] Nielsen, Johannes et al: A Psychiatric-Psychological Study of 50
Severely Hypogonadal Male Patients, Including 34 with Klinefelter's
Syndrome, 47,XXY;
Acta Jutlandica XLI: 3, Skrifter fra Århus Universititet, Munksgaard
1969
[xl] Forssman, H. et al: Children with supernumary X-chromosome. A
ten-year follow-up study of schoolchildren in special
classes;
J.Ment.Defic.Res, Vol 23, Sept.1979: 189-193; Nielsen,
Johannes & Pelsen, B: Follow-up 20 years later of 34 Klinefelter males with
karyotype 47,XXY and 16 hypogonadal males with karyotype
46,XY; Hum.Genet,
Vol 77, Oct.1987: 188-192
[xlii]< font
size="2"> personal correspondence with Professor
P.A.Jacobs
GENERAL
REFERENCES
Concise Medical
Dictionary (Oxford Reference) (4th edition) OUP,
1994
Human Anatomy and
Physiology by: Carola, Harley & Noback: (2nd edition)
McGraw-Hill, 1992
Nielsen, J:
Klinefelter's syndrome: an orientation; Gallo Tryk, Denmark,
1991 (2nd edition); latest edition available
through
Turner Centre's internet site at:
http://www.aaa.dk/turner/tfsen.htm or free for KS men or the parents
of KS boys, via E-mail at: [email protected] or by writing to:
Turner Centeret, Skovagervej 2, DK-8240 Risskov, Denmark.
(tel: +45 86 17 77 77 ext 3684 - Danish
time = GMT +1 hour)
A single photocopy may be
made for private use, without prior permission.
This document may be
quoted from, so long as attribution is given to the author, above.
Doctors & other
professionals helping people with Klinefelter's syndrome may make
copies for their patients & medical students,
etc.
Klinefelter
Organisation (formerly the Klinefelter's Syndrome Club
UK- KSCUK) is a
national voluntary organisation which relies on private
donations and members' subscriptions. We are a self-help
group.