thoughts and ideas about XXY

some thoughts ….

– a survey of XXY about being left-handed or right-handed

( I recently found out with help of an autism specialist that I’m actually left-handed explaining a lot of difficulties with direction of rotation since childhood)

– a survey of XXY about enhanced sensory perception (yes/no, and which senses are affected most often: hearing, visuals, taste, tactile, smell)

(there are communalities between small-scale polls in autism forums and the british XXY forum, both resulting in enhanced sensory issues with hearing and visuals)

if ADD/ADHD are rather symptoms than syndroms (about 50 % of people with autism also have ADHD, about 60 % of people with XXY have also ADHD), and mainly the result of different sensory perception…. it would mean that XXY is one of many possible conditions to obtain a different perception in general.

The idea of, e.g. self-stimulating behavior or special interests as a strategy to manage too much incoming information, social stress, sensory overload, mental overload, etc… is relatively new (but included in the latest DMS-V for diagnosing autism spectrum conditions). If both behavior (stimming and special interests) is less defined, people have to look for other „bad“ copying strategies, like frequent meltdowns, attention deficits, hyperactivity, etc…

(in the few studies about autistic symptomes in XXY, XXY reveal less special interests, repetition behavior as non-XXY autistic people, which could mean that XXY are less able to self-regulate themselves)

Attending symptoms like bad time management, organisation, planning, etc… are shared by all conditions (XXY, ADHD, autism) as a result of executive dysfunctions (something’s working wrong in the frontal lobes).

For a long time, in Germany even now, nobody thought of communalities between these conditions because all symptoms were related to the lack of testosterone. This is another fact I’m quite curious about because hormone imbalances are also reported in autism (and gender dysphoria seems to be more frequent in autism than in the general population), and some autistic women reported too high testosterone values.

I guess the discussion about these relations often stutters because of the usage of the term „autism“: Autism is highly negatively connotated. Nobody wants to be referred to. Parents are often shocked even hearing about this possibility. I approach this topic rather from bottom-up thinking. I gather as much information as possible trying to puzzle it together. I follow the principle of neurodiversity, i.e., the different perception doesn’t express a disorder but a difference. Maybe, this approach gets lost in this strong desire of having categories and stamps, coming with DSM-V and diagnosis (good read: Frances, Allen (2013). Saving Normal: An Insider’s Revolt Against Out-of-Control Psychiatric Diagnosis, DSM-5).

My intention is not to put XXY in additional categories but to destigmatize the existing categories.

Linksammlung (Querbeet)

Autismus

Autism

Satire

Geschlechteridentität (Gender identity)

47,XXY and Testosterone treatment

Executive dysfunctions

Psychologie allgemein

ADHS (ADHD)

Klinefelter Syndrome

Why I support N#mber

While the german version N#MMER already launched, the english version will be available soon in September 2015 and the worldwide first magazine for people with ADHD and autism edited and written by concerned people themselves. You’ll read interviews with Temple Grandin and Sascha Lobo and…

https://nummer-magazin.de/ see also https://twitter.com/Number_Magazine

a text about 47,XXY as symptomes of ADD/ADHD as well as autism are more prevalent in people with 47,XXY. In my opinion, the magazine covers a lot of difficulties concerning the behavior of people with 47,XXY. I had light bulb moments in nearly every text. As I wrote my text for N#MMER in October 2014, I didn’t have such profound knowledge about 47,XXY, and I looked for proof for any statement in the article. It’s the reason for which the text might have appeared in a school’s magazine rather and is clearly different compared with the other texts. Anyway, I hope I could raise awareness towards the characteristics of Klinefelter/47,XXY. American self-support organisations (like AXYS) assume that a certain number of people with 47,XXY is present among people with autism and ADHD.

To clarify: 47,XXY =/= autism spectrum disorders! The prevalence for autism (and ADHD) is significantly enhanced but far away from 100 % (rather between 10 and 30 % for autism).

Autism Spectrum Disorders and 47,XXY:

Figure 1: The diagram shows the results of the Social Responsiveness Score (SRS) measuring the degree of autistic traits.

  • control group (con): 25
  • extra X: 65 (cut-off for autism: 70)
  • diagnosed people with autism (ASD): 95

Source: https://vimeo.com/130199302

Fig 1. ADI-R-Score

Figure 2: The result of the ADI-R test of autism in the three core domains. The horizontal line depicts the threshold value for clinical relevance, the points mark the individual persons with 47,XXY.

10 persons lied above the cut-off in all domains, 11 persons in 2 domains and 13 in one domain. 17 persons were below the cut-off in all domains. The most prevalent domain has been communication (domain 2), the rarest domain has been stereotype behavior (domain 3). Altogether 27 % of people with 47,XXY fulfilled the diagnose criteria for autism spectrum disorder.

Source: Bruining et al. (2009) bzw. https://factsaboutklinefelter.com/verhalten/

ADHD and 47,XXY:

  • Brian B. Doyle (2006) estimated 80 %
  • Tartaglia et al. (2012) found about 36 %,with the vast majority favoring the inattentive subtype (ADD)
  • Cederlöf et al. (2014) examined 86 000 controls and 860 47,XXY: 6 times higher risk of autism and ADHD.
  • Skakkebaek et al. (2014) founds 63 % ADHD in 47,XXY

Thus there is strong evidence for a link between 47,XXY and ADHD/autism, besides the fact all three conditions show major impairments of executive functions.

  1. Bruining et al. (2009) suggests in figure 2 that domain 3 (rituals, routines and obsessive behavior) is weaker in 47,XXY than in idiopathic (male!) autism.
  2. Tartaglia et al. (2012) states that the quiet subtype of ADHD (also called ADD, without hyperactivity and impulsivity) is dominant in 47,XXY.

Speculating:

People with autism who reveal less symptoms of domain 3 (rocking, flapping, obsessive behavior, mainstream special interests) may be easily overlooked (-> high number of unknown cases in girls and women as well as ‚quiet‘ boys and men).

About 90 % of media reports about attention-deficit disorders deal with hyperactive and impulsive behavior although only 10 % of all tests confirm this diagnose. 30 % of all diagnoses present the inattentive subtype with quiet, non-disturbing dreamers. (the remaining 60 % present the combined type), source: http://weltsichtig.de/typisch-adhs-aber-halo/

Thus there is a large number of unknown cases, again in girls and women with ADD but also quiet boys and men).

If the phenotype of 47,XXY is similar to that of females with ADD and/or autism, both neurologic conditions will be discovered more infrequently in 47,XXY (boys with 47,XXY are often described as shy, passive and quiet).

Result:

Therefore it is important to use any opportunity to address these potential secondary diagnoses as therapeutical approaches, national support and accomodations are much better for people with ADHD and/or autism than for people with a diagnose „Klinefelter syndrome“. Moreover, addressing the hormone deficit is not sufficient to treat all side-effects of having Klinefelter syndrome:

Surprisingly, testosterone levels were not associated with these psychological and social health measures, even though low testosterone has been widely believed to underlie many of these symptoms. “Based on this finding, it is not clear that the testosterone therapy commonly given during puberty will remedy many of the problems that children with Klinefelter syndrome experience,” says Dr. Fennoy.

Whether hormonal therapy plays a role during development or not, the researchers emphasize that early intervention to address psychosocial health risks will help patients and their families manage some of the chronic aspects of Klinefelter syndrome.

Source: http://newsroom.cumc.columbia.edu/blog/2015/08/25/developing-a-new-tool-to-detect-a-frequently-missed-sex-chromosome-disorder-in-boys/

What people with 47,XXY and relatives can do:

If you have the feeling there is more to you than low testosterone values and associated infertility, go to a psychiatrist or psychologist.

When people with 47,XXY are bullied in school, physical appearance may be the cause (weak muscles, body composition, breast development, shame having a shower or in the changing room) but also autistic behavior (difficulties with coordination, shyness, bluntness, naivety, imitating others, isolation and more prone to be a victim). Please take care of your children not to be in agony throughout their school time! They will suffer from bullying, post-traumatic anxiety and depression also throughout their lifetime.

Receiving a dual or secondary diagnose will provide additional therapy approaches and support besides hormone replacement therapy.

It’s essential to inform your environment and the relative’s environment about 47,XXY. If physical symptomes are merely present but behaviorial symptomes are more obvious, it probably makes no sense to hold a long talk about Klinefelter syndrome. A lot of people who are not familiar with Klinefelter may conclude that Klinefelter is equivalent for hormone deficit, needs hormone therapy and subsequent all deficits will be cured. Then it’s possibly more senseful to inform about the secondary diagnose. The genetic reason is rather interesting for academics.

Draw your information and guidelines from concerned people themselves! I linked numberous autistic bloggers in my blog writing about their life and everydaylife with autism. Be skeptical when doubtful things arise like cure of autism with helpf of diets, glute-free food, homeopathy, MMS, etc. A great majority of enlightened people with autism rejects ABA and Autism-Speaks.

Read and spread the word for N#MBER! Diagnosed 47,XXY could be helped with additional diagnoses addressing their psychosocial health. Diagnosed people with autism and/or ADHD might have a genetic underpinning of their presumed primary diagnose. It doesn’t mean that the diagnose is wrong but physical health may also play a role, like enhanced risk for cardiovascular disease, diabetes, osteoporosis, autoimmune disorders, and cancer.

Brain, behavior and life of XXY people: a new study (2015)

The entire title of the paper is „Neuropsychology and socioeconomic aspects of Klinefelter syndrome: new developments“ by Skakkebaek et al. (2015)

I will summarize the most important findings of the paper and will add some points I missed to be discussed.

Behavior, psychiatric conditions and brain differences:

Verbal abilities are most severely affected, IQ scores are slightly lower than average.

The majority suffers from …

  • delayed early language development
  • general learning disabilities in reading and spelling
  • impairments with production of syntax, phonemic processing, word retrieval, comprehension, encoding verbal information and decreased processing speed, verbal fluency
  • executive dysfunctions related to attention, response inhibition flexibility and planning

In contrast, visiospatial function and performance IQ seem to be unaffected. (1)

There is a charateristic personality profile of XXY people, displaying a higher level of neuroticism (emotional instability) and lower levels of extraversion, openness to experience and conscientiousness.

These data are confirmed by anecdotal descriptions revealing

  • anxiety
  • increased emotional arousal
  • serious emotional difficulties
  • being unassertive
  • quiet
  • passive with withdrawn behaviour
  • having difficulties in approaching new events

Psychiatric conditions associated with XXY

  • Depression (35 % in general population, 70 % in XXY)
  • Anxiety
  • Schizophrenia
  • Autism (prevalence of 1 % in the general population, 11-27 % in XXY)
  • Attention-deficit/hyperactivity syndrome (5 % in general, 63 % in XXY)

XXY is often associated with increased level of psychological distress. Higher levels of emotional instability contribute to increased risk of depression and anxiety.

Brain differences

  • Global brain volume, total brain volume, total gray and white matter volumes were found to be significantly smaller in XXY.
  • Volumes of temporal lobe, hippocampus and amygdala were also smaller.
  • All studies except one didn’t find any correlation between cognitive performance scores and brain volumes.

It is assumed that microchanges of brain structures are more important.

Van Rijn examined the brain activity during social judgements of faces and found that XXY people had decreased activity in brain regions related to face processing (inferior temporal regions) and to the limbic system (amygdala, insula). Two other studies found that decreased language activation and/or decreased language lateralization in the posterior temporal language regions were present.

There is still uncertainty about the exact mechanisms of parental origin of the extra X chromsoome, X-chromosome inactivation and androgen recepter CAG repeat length.

Education, living, mortality and criminality

Several studies suggest that behavioral problems, learning disorders, poor educational outcome and criminal conduct could be seen.

It is also emphasized that many led normal lives and the impact of syndromal effects subsided with advancing age. (2)

XXY men  …

  • have significantly fewer partnerships
  • enter later into such partnerships
  • achieve fewer fatherhoods and for those who had luck they occur later

However, at least 25 % of all Danish Klinefelter Syndrome were registered as fathers, probably mostly due to donor semen donation.

Data also show that …

  • educational level is low leading to a lower income throughout their lifetime and that many retire early (43,5 vs. 60,3 years)
  • mortality is almost doubled, partly influenced by cohabitation and educational status (without them, less prominent)
  • criminality is enhanced for sexual abuse, arson, burglary and ‚other offenses‘ but decreased for traffic crimes (3)

If the social and economic background is taken into account, the risk is generally reduced.

XXY are relatively seldom diagnosed…. There are long delays and frequent-false negatives. Only about 25 % are diagnosed, and the majority has to wait until adulthood.

Several problems follow:

1. all current XXY studies may have selection bias and the present knowledge may not cover the undiagnosed cases.

2. 90 % of XXY remain undiagnosed until after 15 years of age, missing an important window of opportunity for correcting or alleviating the symptoms

3. we should change our current diagnostic strategy and introduce a new one, diagnosing XXY on blood from neonatal heel prick test (Guthrie test).

Early diagnosis would improve

  • cognitive functions, learning, verbal abilities and behavior, if it turns out that early testosterone supplementation is efficient, and that neuropsychological intervention before puberty is effective.(4)
  • the unhealthy body composition, with increased risk of type 2 diabetes and metabolic syndrome seen in adulthood, as well as bone structure.

Future:

Studies are currently missing focusing on proper treatment or intervention to better the phenotype.

neurocognitive deficits, linked to dyslexia and other learning-related problems, may well lead to poor socioal and economic outcome.

A holistic approach is needed.

Conclusion:

The neurocognitive phenotype of Klinefelter syndrome is clearly abnormal (5) and the need for psychological and cognitive treatment in many cases is evident.

*

Remarks on statements:

(1) „visiospatial function“ seems to be unaffected.  Studies by Jay Giedd show that visual and spatial thinking of XXY people are actually a strength of their thinking architecture. So, visiospatial function isn’t only normal but better pronounced. A lot of XXY people have a good visual memory.

(2) The social environment and intervention is very important. In countries and regions with poor density of experienced specialists, therapeutic outcome will be probably less satisfying, and increasing age could strengthen depressive mood and anxiety.

(3) The enhanced risk to commit crimes of sexual abuse [and arson] could probably be related to inappropriate testosterone supplement therapy. Overdosing testosterone might enhance emotional instability and overemphasize masculine behavior of males. It would be interesting to know whether the participants were already taking testosterone supplements and whether on a daily basis (self-medication) or in larger intervals (injections).

(4) It is important to emphasize that testosterone supplement is neither a one-cure-for-everything therapy nor necessarily suited for all children and adolescents. See additional remarks.

(5) The neurocognitive phenotype of Klinefelter syndrome is clearly DIFFERENT.

Additional remarks:

1. Though I know that science in genetics and behavior usually concentrates on deficit thinking in genetic anomalies, it would be helpful for us affected persons to highlight strengths and positive outcome. Anecdotal descriptions reveal enhanced sense of creativity, sensitivity, social justice, honesty, enhanced detail perception, good visual memory/long-term memory, good with animals.

2. In the vast majority of these studies and papers, the term „men or boys with Klinefelter syndrome“ is used, neglecting a minority of XXY people who do not identify as men, for different reasons… Either there are born intersex, or born as transgender preferring to transition into female later as a teenager or adult. Some identify as male but don’t feel well with masculinization through testosterone supplement therapy, either. A few XXY are also reported to have androgen insensitivity syndrome and testosterone therapy will probably not work for them.

One of the most difficult and heavily discussed topics in the XXY community is whether early intervention with testosterone therapy is a benefit for all XXY children, as transgender or persons who don’t want to be masculinized may not be suited to receive additional testosterone or even require estrogen therapy instead.  In these cases, the term Klinefelter’s syndrome referring to hypogonadism (testosterone deficit) doesn not seem to be appropriate.

I hope we – as XXY community and individuals – are able to convince the scientific community to put more focus on gender identity in XXY before recommending one-size-fit-all-cures for young XXY.

3. I missed some lines about sensory processing disorder. There is only one study about that:

Van Rijn et al, Psychophysiological Markers of Vulnerability to Psychopathology in Men with an Extra X Chromosome (XXY), PLoS ONE, 6(5): 2011

confirming sensory gating disorder in XXY (in other words, XXY often have difficulties to filter out background noise/distraction)

The existence of a handout about sensory processing disorder on AXYS as well as several reports about motoric difficulties suggest that sensory processing and integration disorder is likely to be common in XXY.

Anecdotal evidence is furthermore given about enhanced sensitivity to sensory stimuli like noise, light, motions, smell/taste and touch suggesting a crucial commonality with autism spectrum conditions. One should probably think of XXY as possible specific subtype of the large autism landscape.

Myths and facts about Klinefelter syndrome

Parents …

may see the infertility as their greatest concern, oftentimes as a reason to abort given a prenatal gene test before birth. Further obvious difficulties are learning difficulties, less interest in the interaction with peers and partly bullying during school because of a feminine body shape and increast breast tissue development as well as behaviorial issues.

Medical specialists …

tend to equate the karyotype 47,XXY and Klinefelter’s syndrom, and as a result a lack of testosterone which needs to be treated. The hormone deficit is in the foreground and explains most of the effects like shyness, depression, difficulties with peers as well as osteoporose and metabolic syndrome. They often assume that XXY identify themselves as men and want to be masculinized by testosterone supplement therapy.

Employers and colleagues …

are often unfamilar with the effects of Klinefelter’s syndrome and prefer a look at wikipedia. However wikipedia and other sites do not always inform about the genetic origin and its large spectrum of different effects. Main risk is that they assume all effects were present and they do not check its validity for each individual XXY person. Moreover, they will likely think testosterone deficit is the core symptom and hormone replacement treatment will be sufficient to treat anything negative in the person, or which is interpreted as negative (not every derivation from the norm is necessarily a deficit). If deficits are present, they may be compensated by strengths which may be relevant for employers as well but talking about Klinefelter’s syndrome implies talking about deficits and disabilities. XXY is more than a deficit – it’s just a different way of being.

XXY themselves …

  • got luck and do feel barely any effects of having a second X
  • feel effects but do not know the reason for it (large number of unknown cases)
  • feel effects and know about the diagnosis but do nothing more than testosterone treatment because they think it’s sufficient (correct for some, not for all)
  • feel effects and suffer from not having specialists and other XXY people to share knowledge and questions
  • disclose to others and seek for open exchange with XXY peers and specialists

And what about me?

My picture of Klinefelter Syndrome changed over the recent eleven months quite a lot, and now I’m not even sure what it is exactly and which associations are given between different causes and effects. I try to separate because I think it’s for nothing to stuff as much symptoms as possible into the umbrella Klinefelter syndrome or XXY, and XXY individuals have only a few but not all of these symptoms. Another XXY person will not identify with these symptoms and might be afraid of to be stigmatized for something he actually has not.

My current state of knowledge, basing upon the collected references of about 70 scientific papers, exchange with other XXY and relatives as well as researchers and physicians:

Please keep in mind I’m not a doctor and I can’t guarantee there is a state of latest research different to my current knowledge.

1. The genetic signature 47,XXY is the sharing feature of us, except for the mosaic form 46,XY/47,XXY

2. Klinefelter’s syndrom is the description of physical symptoms in nine (9!) men by the first report of Harry Klinefelter in 1942.

3. Hypogonadism (low testosterone values) are present in nearly all XXY people as a result of the second X chromosome. Which genes are causing hypogonadism? Still unknown.

4. Low testosterone values cause decreased attention and libido, increased tiredness, mood swings, enhanced tendency for depressions, and infertility (in interaction with overproduction of the sex hormones FSH and LH)

5. Partly genetic, partly hormonal effects produce a female-like fat/muscle distribution and different body composit as well as enhanced risk for osteoporosis and metabolic syndrom.

6. Rather due to genetics than to hormonal effects are problems with executive functions, e.g. bad short-term memory, impuls control and target-orientated action and sensory integration disorder (gross and fine motorics, oversensitivity to incoming stimuli), as well as dyslexia

7. Deficits of executive functions and sensory integration disorder play a major role in psychiatric conditions like ADHD, autism and schizophrenia whereas Klinefelter’s syndrom is mainly seen in connection with testosterone deficits.

8. Testosterone deficit does not evolve before puberty, with exception of the missing mini-puberty in the first three months after birth (not every XXY is missing that period when testosterone levels rise to adulthood levels for a very short time). Some adults even have normal testosterone values (who defines normal? from a XY perspective? Is XY also valid for XXY? What is normal for us?). For intersexual and female XXY, testosterone deficit may even be the wrong term. They just have low testosterone values and may start estrogen therapy later. There are also XXY males who agree with their female characteristics and traits and do not consider low testosterone values as a deficit. They would even put up with health issues due to the low values instead of losing their identity. If neither gender nor identity argue for a testosterone deficit, the XXY person should not be considered to have Klinefelter’s syndrome.

9. Deficits in language skills, verbal expression and in communication in general are often compensated by thinking in pictures or patterns as well as enhanced detail perception.

What’s the difference between my approach and the common medical approach?

I do not start with a testosterone deficit but with a genetic condition (as a neutral judgement, without moral evaluation).

All further effects are the consequence of a genetic condition but not of a syndrome encompassing  different causes – both genetics AND hormones.
Overview:The list above is not complete but should serve as a rough simplification of my way of thinking about XXY. The term Klinefelter’s syndrom is removed from that overview because it’s only a part of all these circles and just a cut-set in the list. There is no case with a 100 % concurrence as even testosterone deficit is not the accurate term for female XXY.In a strict sense, the listed characteristics are part of the diversity of the genetic condition XXY which may also present in all people with normal chromosome numbers.The additional X only enhances the prevalence for these characteristics.

If you’re asked what you have and how to explain it …. instead of saying „I have Klinefelter’s syndrome“ you may say

I have lower testosterone values, a different metabolism, a different perception (sensory gating disorder) and another way of thinking. They are the result of my genetic condition.

The genetic condition already comprises the hormonal effects which will appear differently in individual XXY persons.