Integrating Genomic Medicine into Mental Health Nursing – Part 3 (Chromosomal Disorders and Copy Number Variants)

In this third post in a series on Genomic Medicine in Mental Health Nursing, we will examine how chromosomal changes and gene copy number variation can result in syndromic presentations that have a strong mental health component to them. This may be important to acknowledge, as many individuals with chromosomal disorders or pathogenic copy number variants may currently go undiagnosed. The recognition of chromosomal presentations could lead to better diagnosis and clinical management – not just for affected individuals, but also for their close family members.



Making Sense of Cytogenetic Terminology

I appreciate that there is much terminology from the field of genomics that may be unfamiliar to many mental health nurses. Here are some quick definitions to help the uninitiated. Follow the links for more comprehensive definitions:

  • Cytogenetics: The study of the structure and function of chromosomes, including how changes to them can lead to differences in clinical presentation (or phenotype).
  • Chromosome: Large and tightly packaged length of genetic material, containing multiple genes. Healthy individuals have 46 chromosomes in their genome: 22 pairs of autosomes (the numbered chromosomes seen in males and females), and a pair of sex chromosomes (XX for females & XY for males).
  • Karyotype: A medical image that shows all of the chromosomes within a person’s genome – like the picture at the top. In karyotypes, chromosomes are manually grouped together, from Chromosome 1 to 22, followed by the sex chromosomes. The term can also be applied to a verbal description of an individual’s chromosomal make-up. e.g. the picture at the top of the page shows a 46, XY karyotype.
  • Parts of the Chromosome:

Different chromosomes may be of slightly different shapes and sizes, but they all have some common features:

  • Telomeres: Areas without genes at either end that help to keep the chromosome intact, and have been associated with the aging process.
  • Centromere: Constricted region along the chromosome. This region is also lacking in genes and it plays a crucial role in chromosomal replication. It always seems to be off-center, leading to shorter and longer arms above and below it.
  • P & Q Arms: These make up the majority of the length of the chromosome, and contain all of the chromosome’s genes. The shorter arm is referred to as the p arm, and the longer arm as the q arm. These letters can be used along with numbers to describe the position of genes along the chromosome (its locus). e.g. The gene responsible for causing Huntington’s disease (HTT) can be found at position p16.3 on Chromosome 4.

There are then some terms used for variations to the standard arrangement of 46 chromosomes in a person’s genome:

  • Aneuploidy: An unusual number of whole chromosomes found within a cell. This can mean too many, as seen with Trisomy 21 (Down’s Syndrome), but can also mean too few, as seen with 45, X (Turner Syndrome).
  • Chromosomal rearrangements: Traditionally, these can be seen as fairly large-scale deletions or insertions, where chunks of a chromosome are missing or have been replicated, or as translocations, where a chunk of one chromosome can relocate – often to another chromosome.
  • Copy number variants (CNVs): This may be seen as a specific type of chromosomal rearrangement, where much smaller parts of a chromosome are deleted or inserted. This results in differing numbers of a specific gene being present in an individual. This is a surprisingly common occurrence throughout the human population, with all of us showing differing numbers of particular genes from our neighbours. Sometimes, this may have little or no noticable effect; sometimes it may impact on certain physical characteristics, like how we metabolise food or medications. However, there are instances when CNVs are associated with disease states.
  • Syndrome: A wide variety of signs and symptoms that characterise a disorder, usually deriving from pathogenic changes to a range of organ systems. As chromosomal disorders usually affect the function of multiple genes, these disorders are often referred to as being syndromic.


Because of the syndromic nature of chromosomal abnormalities, we tend to see a high level of them resulting in learning disabilities and learning differences. The presence of dual diagnosis services around the country attests to the notion that there is a high level of comorbidity between learning disabilities and mental illness. The nature of these co-morbidities may not always be clear: Challenges with various aspects of cognition (or physical health) could potentially lead to mental illness through various significant pyschosocial stressors; alternatively, there may be shared neurodevelopmental or neurodegenerative mechanisms. We also need to consider that people with learning disabilities (LDs) will display signs and symptoms of mental illness differently from those without LDs (See Section 1.8 onwards of these NICE Guidelines). However, to keep the length of this blog post manageable, these discussions will not be included here. Below, I have merely listed some chromosomal disorders and described some commonly found concurrent mental health conditions with them.



Aneuploidies and Mental Illness

Links within the names of the following conditions will lead to factsheets from The Society for the Study of Behavioural Phenotypes (SSBP).

Down’s Syndrome (Trisomy 21)There is a high level of variability in the clinical features of Down’s Syndrome (DS), and this includes individuals’ presenting behaviours and mental state. Compared to other forms of LD, people with DS are less likely to display maladaptive behaviours. However, compared to the general population, there is a greater likelihood of oppositional behaviors, impulsivity, and inattention. Around 10-15% of individuals display symptoms of Autism Spectrum Condition (ASC), whilst 6% show signs of Attention Deficit / Hyperactivity Disorder (ADHD). Mood disorders and anxiety disorders are also more prevalent than the general population. During adolescence and early adulthood, a small subset of individuals with DS show signs of  Down Syndrome Disintegrative Disorder, whereby previous skills and levels of independence are lost, and individuals show signs of disinterest and withdrawal. It has been speculated that this may occur after an individual experiences significant emotional stressors. There is a greatly increased likelihood of the development of Alzheimer’s disease, and at an earlier age of onset. The average age of Alzheimer’s Disease diagnosis is the mid-50s, and there is greater than an 80% chance of symptoms by the age of 65.

Turner Syndrome (45, X): As there is no Y chromosome, individuals with Turner Syndrome are all biologically female. Many challenges tend to manifest at the point of adolescence. Individuals with Turner Syndrome will not spontaneously experience the development of secondary sexual characteristics due to a lack of oestrogen production. However, other issues also present at this time. Young women will not experience the growth spurt associated with puberty, and neurodevelopment is also affected – in particular the ‘social brain’. Some of the delays in adolescent development can be mitigated through the use of growth hormone and oestrogen supplements. It is suspected that symptoms of mild ASC are widespread in adults with Turner syndrome, as are symptoms of anxiety – with particular difficulties around social anxiety and low levels of self-esteem.

Triple X Syndrome (47, XXX): As with Turner Syndrome, all individuals are biologically female. Challenges with mental health and cognition are also similar to what is observed with Turner Syndrome. Social cognition is likely to be affected, with some individuals showing signs of low self-esteem and social anxiety. Mild executive dysfunction and mild ASC-like symptoms may also be present. Individuals with Triple X may find it harder to cope in stressful environments; there may be a higher prevalence of mental illness in general amongst this population.

Klinefelter Syndrome (47, XXY): Because of the Y chromosome, all individuals are biologically male. However, following puberty, individuals are likely to develop narrow shoulders, broad hips, sparse body hair, gynecomastia (the growing of breasts), and insufficient testicular growth. Individuals are also likely to be infertile. Fertility, together with male characteristics can be induced through use of supplemental testosterone. Hormonal treatment at puberty can induce masculine secondary sexual characteristics, increase fertility, and reduce the likelihood of anxiety, mood dysregulation, symptoms of ADHD, and problems with self-esteem, and socialization (especially around abilities of social expression). Early treatment in infancy and early childhood mitigates physical, cognitive and mental health risks further, highlighting the value of prenatal diagnosis of the condition.

XYY Syndrome (47, XYY): Individuals will have an increased likelihood of showing signs of ADHD, autistic spectrum condition, distractibility, impulsivity, challenges with temper management, and problems with social relatedness. They are also likely to experience speech delay and reading difficulties. As with Klinefelter syndrome, early recognition and hormonal treatment can reduce neurodevelopmental deviations. Suspected associations with criminality and social deviancy are unsubstantiated and counterproductive; these views should be challenged.



Other Relevant Chromosomal Alterations

Although there is the scope for a virtually limitless number of different deletions, insertions, and translocations, there are a few recurring chromosomal abnormalities that result in the development of particular signs and symptoms of mental illness. Again, most information has been taken from factsheets by The Society for the Study of Behavioural Phenotypes (SSBP).

22q11.2 Deletion (or DiGeorge) Syndrome: Although relatively common (estimates as high as 1:3000 births), it is considered to be underdiagnosed. The associated microdeletion to Chromosome 22 affects multiple genes, and can occur spontaneously or be inherited in an autosomal dominant manner. The severity of the syndrome can vary between mild and life-threatening. Children with the deletion may present with symptoms of ADHD, OCD, ASC, or a range of anxiety disorders. Adults are at a greatly increased risk of depressive and psychotic disorders.

16p11.2 Duplication Syndrome: This shares a lot in common with DiGeorge Syndrome. It is estimated to affect 1:2500 individuals with mental health problems but is considered to be underdiagnosed. It too can occur spontaneously or be inherited in an autosomal dominant manner. Carriers are often diagnosed with ADHD, and sometimes with ASC. Adults are at significantly increased risk of developing anxiety, depressive and psychotic disorders.

There are a number of other chromosomal syndromes that, although have a mental health component, are more commonly associated with pronounced learning disabilities and physical health complications. If you would like to know more about these, just follow the links below:


Copy Number Variants and Schizophrenia

The information below has been taken from the Royal College of Psychiatrists report on The Role of Genetic Testing in Mental Health Settings. In particular, see chapter 3.

Differences in the number of particular genes within our genome can also increase the risk of schizophrenia and other neurological conditions by up to 10-fold. There are now 11 known CNVs that are associated with schizophrenia, and also with conditions such as learning disabilities, ADHD, ASC, and epilepsy. Although these CNVs may be individually rare, collectively they are relatively common. It is estimated that 2.5% of individuals with schizophrenia (1 in 40) have one of these CNVs.

There is a 50-50 chance that if a person with a CNV has children, that CNV will be passed on. This leads to an autosomal dominant pattern of inheritance.

For a full list of these CNVs, together with a deeper investigation into their characteristics, please see the article by Kirov et al. (2015).



Why This Matters as a Mental Health Nurse

  • With conditions like Turner Syndrome and Kleinfelter Syndrome, the sooner the condition is known about, the sooner medical interventions can be put into place. Hormonal treatment during childhood can significantly improve the quality of life of service users cognitively, physically and emotionally.
  • With deletions and CNVs, receiving a positive diagnosis from a genetic test can:
    • Lead to genetic counselling for a family, where the likelihood of other family members being affected, together with family planning options, can be discussed.
    • Provide answers to questions about why schizophrenia may have developed for an individual.
    • Prompt testing for ADHD or ASC if the chromosomal change is also associated with that form of neurodiversity.
    • Manage the risks of physical health problems. e.g. if the chromosomal change is associated with cardiac complications, then ECGs can be conducted, a cardiology referal can be made, and antipsychotics like clozapine can be avoided.

Picture References


Information Source References

Posted by Ben Murphy

Ben is a registered mental health nurse, holds an MSc in Genetic Counselling, and is a lecturer in Biological Sciences at City, University of London. Amongst other things, he teaches anatomy, physiology, pathophysiology and therapeutics to pre-reg. and post-reg. nursing students.

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