Klinefelter's Syndrome Association

These pages provide information on Symptoms, Indicators and Diagnosis (SID). The KSA gratefully acknowledges the award of a grant from the British Society of Endocrinology without which the Consult SID pages would not have been feasible.

Much of the information available about KS is related to how it affects males because the syndrome was first identified in a group of males. Consequently, SID concentrates on the affect low or zero testosterone has on males. But like the general population there are people who have KS who do not consider themselves to be male; more research is needed to determine how KS impacts these people as they may require different medication, such as, oestrogen in preference to testosterone. As that data becomes available the KSA will add to these pages. In describing the symptoms associated with KS the KSA has used extracts from its Members Binder, from other KSA publications, desk based research and from polls conducted via the KSA's international talk forum www.XXYTalk.com.

To understand how KS can impact a man, imagine if you were a man and had low or zero testosterone; you would have no energy, you would lack motivation and strength, you would have a tendency to be overweight and maybe develop female breasts which would adversely impact on your self-esteem, you would have poor communication and social networking skills, you would be shy - even introverted. You would suffer from a short span of attention; have poor memory being unable to recall recent conversation or instructions. Not surprisingly others may well have seen you as lazy, stupid and indolent. That is the difference a lack of testosterone makes and is the reality of life for many men with Klinefelter's Syndrome because their bodies do not produce testosterone.

Unfortunately KS is often diagnosed late in life (at over 35 years of age) when much of the damage in terms of physical, mental and social health has been done. As a result many KS males suffer the long-term effects of low or zero testosterone, such as, osteoporosis, obesity, diabetes, heart conditions, extreme tiredness or lethargy, depression, gynaecomastia (breast development), infertility, mood swings, mental health conditions, the list goes on and on. However, not ALL KS males suffer from ALL these symptoms. Nor do ALL KS males suffer extremes. Each case of KS needs to be individually assessed. For example, some of our members are in wheelchairs by the time they are in their mid-twenties due to osteoporosis while others are active sportsmen, some have essential tremor by the age of 50 while others do not, some have diabetes while others do not. Early diagnosis and appropriate treatment can make a huge difference!

Symptoms of KS

The symptoms of Klinefelter's Syndrome vary considerably between individuals and the severity of the condition is associated with the number of extra x sex chromosomes the individual has. The most commonly recognised symptoms are associated with under functioning testes and include:

• Very small testes
• Infertility
• Gynaecomastia ( male breasts)
• Low levels of testosterone
• Tall stature with disproportionally long legs and arms (euneuchoidism)
• Lacking or sparse body and facial hair
• 'Female type' body and fat distribution
• Flabby or poor muscle tone

Other common features associated with KS include:

• Varicose veins of the lower legs and poor circulation
• Low bone density
• A predisposition to thrombosis
• Depression and mood swings

In addition to these symptoms there are other symptoms which can be broken down between children and adults.

Additional common symptoms in children include:

• Speech and language development disorders
• Short attention span or easily distracted
• Lack of agility and dislike of physical games, especially team games
• Passive, shy
• Trouble with self expression
• Moderate learning difficulties
• Inability to speak coherently, almost speaking too fast

Additional common symptoms in adults include:

• Tired or lethargic for no apparent reason
• Low sex drive/libido
• Poor upper body strength
• Passive, shy
• Low self-esteem
• Difficulty remembering recent conversations
• Poor communication skills

Low intelligence was once seen as a symptom, however, in recent years this has been questioned. Bearing in mind the speech and language development disorders, a short span of attention, trouble with self expression, shyness and other learning difficulties it could be that it is a lack of understanding by the educational system that is at fault not the intelligence of a child diagnosed with KS. A highly useful publication, available via the Free Downloads, is "The Learning Needs of Boys with KS: Information for Teachers and Parents" by Paul Collingridge.

Another point of view is that children diagnosed with KS develop at a slower rate than ordinary children. To quote Onnineko of XXYTalk.com "The development time of the typical person is very short. It is well known that a child learns both better and faster than an adult. An XXY child develops over a period considerably longer than an XY or XX child, about 8 more years. Society for 99% of the world believes that at 18, the child is mature. However, XXY children mature at about age 25. If we compare an XXY child at their point of relative maturity at age 25 to an 18 year old, the 25 year old child is significantly higher on intelligence tests."

A survey of members of XXYTalk.com, the KSA's international online talk forum found the following symptoms in order of highest frequency first representative of persons diagnosed with KS:

Indicators

Because the range of symptoms in persons with Klinefelter's Syndrome is so varied the KSA sought to identify some alternative reason why a GP or any medical professional might decide to investigate the possibility that a patient had KS. Whatever this reason was or reasons were it/they would need to be readily obvious in a private consultation. Looking at the most common symptoms we know that approximately 80% of males with KS have small testicles. But if a patient saw a GP complaining of lethargy, depression and inability to concentrate then it would seem hardly appropriate if the GP asked the patient to strip so that they could examine his testicles!

Because 80% of those diagnosed with KS have small testicles we can expect low to zero levels of testosterone. Were there any obvious indicators of low testosterone? Researching possible indicators revealed various studies ranging from the ability of a person to dance to size of ears. Most of these studies were not vigorously evaluated, they were not statistically proven, that is except for one! Research by Prof John T. Manning over decades had proven time and again that the ratio between the index finger and the ring finger was influenced by the level of testosterone. This would be a highly suitable 'indicator'; all a GP would need to do was ask the patient to hold out his hands, palm up and fingers together and then the GP could visually gauge the length of these two fingers on each hand. If the fingers were of similar length or that the index finger was longer than the ring finger then this would indicate a good chance that the patient had low testosterone and justified further tests.

To check if this might be a suitable indicator the KSA via its talk forum XXYTalk.com carried out an online poll requesting the membership to compare their finger lengths. The results were 41% had an index finger and ring finger of the same length, 22% had an index finger that was longer than the ring finger, and 37% had an index finger that was shorter than the ring finger. Although this was not a scientific study the results do suggest that 63% exhibited low testosterone features and therefore there could be a link that would justify further research.

To be accepted by GPs and the medical profession the KSA recognised that a full blown academic study specifically looking at the finger ratios of persons diagnosed with KS would be required. The findings would be analysed by professionals and published in peer refereed journals to further validate the results. To this end the KSA instigated in cooperation with Prof Manning a research project looking into this area in April 2011. Initial results are expected in time for the KSA's Annual Conference to be held at the Priory Street Centre, in York, Yorkshire on the 24th of September 2011. For more information go to Research, 2D:4D.

A brief explanation of the rationale behind the 2D:4D ratios and KS research is provided below:

Testosterone shows two peaks of production during development. The first occurs in the foetus at the end of the first trimester of development. The second occurs at puberty. It is thought that the prenatal peak is concerned with “organizational” changes to the foetus, and these changes sensitize the individual to the effects of testosterone at puberty.

Digit ratio (the ratio between the length of the 2^nd or index finger and the 4^th or ring finger: 2D:4D) is thought to be a marker of foetal levels of testosterone. That is, a long index finger relative to ring finger indicates low foetal testosterone. If this is correct we would expect KS individuals to have long index fingers relative to their ring fingers.

This study will test this hypothesis. Images of fingers (from photocopies of the palm of the hand) will be measured in order to quantify the typical 2D:4D in KS. This will then be compared to the typical 2D:4D of men in the population. If the difference is large it may be that 2D:4D could be helpful in the diagnosis of KS.

An example of the palms of a man diagnosed with Klinefelter's Syndrome and karyotype 47XXY is shown below:

Diagnosis

The first thing to check if KS is suspected in a man are the levels of LH (Lutenising Hormone), FSH (Follicle Stimulating Hormone) and Testosterone in the blood.

As testosterone levels are at their highest early in the morning (around 8.00 am to 9.00 am) blood tests for testosterone should be taken around this time for accuracy. Levels taken at different times of the day will be lower and therefore unreliable.

Normal Testosterone Levels (Royal Free Hospital): 9.9-28.5 nmol/l. It must be pointed out that the range varies between different laboratories. LH stimulates testosterone production from the testicles. Testosterone in turn regulates LH secretion by a process called 'negative feedback'. LH secretion is therefore under restraint from testosterone. Similarly, FSH stimulates sperm production in the testicles, as well as, stimulating production of inhibin B from the testicles. The latter is responsible for restraining FSH production from the pituitary, by negative feedback'.

When the testicles are severely damaged, both testosterone and inhibin B production are reduced, removing the restraint of these hormones on the hypothalamus and pituitary, leading to high levels of LH and FSH. The LH and FSH levels are higher than normal because the pituitary is working 'extra hard' to try and stimulate the testes, which are not responding because they are either damaged or absent. This type of hypogonadism is also called primary hypogonadism (i.e. the testes are the primary cause of the hypogonadism).

High LH, FSJ and low testosterone levels on their own do not simply occur in KS; there are other causes for raised LH and FSH and low testosterone levels. A generic test (karyotype) is required to confirm diagnosis. Semen analysis generally shows absence of sperm in the ejaculate and a bone density scan (DEXA Scan) may reveal osteoporosis (thinning of the bones).