Basic Neurosciences · Paper A
Chromosomal abnormalities
Several genetic conditions, caused by missing or extra chromosomes, carry distinctive physical features and psychiatric or learning consequences that the exam expects you to recognise. For example, imagine a young adult with a history of cardiac surgery, cleft palate, and low calcium who develops psychotic symptoms. In practice, that combination should raise suspicion of 22q11.2 deletion syndrome, which carries a notably high schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more → risk.
Klinefelter syndrome (47,XXY) gives a tall male with small testes, breast development and mild learning difficulty. Turner syndrome (45,X) gives a short female with a webbed neck and largely preserved verbal IQ. Down syndrome (trisomy 21) causes learning disability and almost universal early Alzheimer-type changes (the amyloid gene sits on chromosome 21). The 22q11.2 deletion (DiGeorge) brings heart defects, cleft palate, and about a 25% lifetime risk of schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more →, a key exam fact. Picture a tall adult male with reduced fertility and mild learning difficulty. In practice, that combination points to Klinefelter syndrome rather than another chromosomal condition.
A chromosome is one of the thread-like structures in a cell's nucleus that carries DNA (the molecule that stores genetic instructions). Most chromosomal abnormalities are first picked up in paediatrics or genetics clinics, but several cause a recognisable pattern of intellectual disability, behavioural features, and psychiatric risk that turns up repeatedly in psychiatry exams. The skill being tested is not memorising every syndrome in exhaustive detail: it is matching each named condition to its chromosome, its core physical or behavioural pattern, and its single most testable psychiatric association.
A chromosomal abnormality is a change in the normal number or structure of chromosomes. Humans normally have 46 chromosomes arranged in 23 pairs; a TRISOMY is an extra copy of one chromosome (three copies instead of two), a MONOSOMY is a missing copy, and a DELETION is a missing segment of a chromosome rather than the loss of the whole chromosome. Every named syndrome below is defined by exactly which of these three things has happened, and to which chromosome.
A common mistake is assuming every chromosomal syndrome causes an obvious, severe physical abnormality that would be impossible to miss at birth. Some, like 47,XXY (Klinefelter syndrome) or 45,X (Turner syndrome), can present subtly, sometimes not diagnosed until adolescence or adulthood, when infertility, learning difficulty, or a psychiatric presentation prompts genetic testing. Do not assume a chromosomal cause has already been ruled out just because a patient looks physically unremarkable.
Imagine three patients, each carrying an extra copy of one chromosome. The first has an extra chromosome 21: Down syndrome (trisomy 21), the most common survivable trisomy, associated with characteristic facial features, congenital heart disease, and a raised lifetime risk of early-onset Alzheimer's dementia, because the gene for amyloid precursor protein (APP, the protein that gets cut up into the amyloid plaques seen in Alzheimer's) sits on chromosome 21. The second has an extra chromosome 18: Edwards syndrome (trisomy 18), a much more severe condition with a low survival rate beyond infancy. The third has an extra chromosome 13: Patau syndrome (trisomy 13), similarly severe, associated with midline defects such as cleft lip and palate. Learning WHICH chromosome is extra, and that survivability drops sharply moving from 21 to 18 to 13, is the fastest way to keep these three apart under exam pressure.
The sex chromosome syndromes work differently from the trisomies above. Klinefelter syndrome (47,XXY) is an extra X chromosome in a male, giving a 47,XXY karyotype (karyotype = the full chromosome count and pattern of an individual, read out from a blood test). It is associated with tall stature, reduced fertility, and a raised risk of learning difficulty and mood or anxiety disorders compared with the general population. Turner syndrome (45,X) is a single X chromosome with the second sex chromosome missing entirely, giving a 45,X karyotype in a female; it is associated with short stature, ovarian failure leading to infertility, and characteristic features such as a webbed neck, though verbal intelligence is usually preserved even when specific difficulty with visuospatial tasks is present.
Two further conditions matter for different reasons. Fragile X syndrome is caused not by an extra or missing chromosome but by an expanded CGG repeat sequence in the FMR1 gene on the X chromosome, which silences the gene; it is the most common inherited cause of intellectual disability and is strongly associated with autism spectrum features, hyperactivity, and anxiety. 22q11.2 deletion syndrome (also called DiGeorge syndrome or velocardiofacial syndrome) is a missing segment of chromosome 22, causing congenital heart disease, cleft palate, and immune problems: and it carries the single highest known genetic risk for later of any identified chromosomal abnormality, which is exactly why it keeps appearing in psychosis-related exam questions.
A chromosomal abnormality (a whole-chromosome or large-segment change, detectable on standard karyotyping) needs to be told apart from a single-gene mutation: for example, Huntington's disease is caused by a mutation within one gene on chromosome 4, not by a change in chromosome number or a large segment. It is also different from an epigenetic change, where the DNA sequence itself is unchanged but gene expression is switched on or off by chemical modification of the DNA. Within the chromosomal group itself, the exam-relevant confusions are the three trisomies (21 vs 18 vs 13, distinguished mainly by survivability and severity), and the two sex-chromosome syndromes (Klinefelter's extra X in a male vs Turner's missing second sex chromosome in a female, which are opposite in both the sex affected and the growth pattern: tall in Klinefelter, short in Turner).
Diagnosis rests on karyotyping, a blood test in which chromosomes are stained and counted under a microscope, or on more targeted genetic testing when a specific small change is suspected. FISH testing (fluorescence in situ hybridisation, a technique that uses a glowing molecular probe to check whether a specific piece of DNA is present) is used for microdeletions such as 22q11.2 that are too small to see on a standard karyotype. CGG-repeat analysis, a molecular test that directly counts the repeat length in the FMR1 gene, is used for Fragile X syndrome rather than karyotyping. Testing is usually prompted by a recognisable pattern of physical features, developmental delay, or a specific psychiatric presentation, such as early-onset psychosis in a young person who also has a congenital heart defect.
There is no cure for the chromosomal abnormality itself, so management is multidisciplinary and follows condition-specific guidance rather than a single universal pathway. Genetic counselling (a structured discussion of what the diagnosis means, recurrence risk, and whether other family members should be tested) is offered across all of these syndromes. NICE guidance on autism and learning disability shapes the behavioural and educational support offered in Fragile X syndrome, while a patient with 22q11.2 deletion who develops psychosis is managed with first-line antipsychotic treatment and psychological therapy per NICE's psychosis and pathway, alongside ongoing cardiac and endocrine follow-up for the syndrome's physical features. Klinefelter and Turner syndromes are followed jointly by endocrinology, for growth and fertility, and, where needed, mental health services for the raised rate of mood and anxiety difficulty.
If a vignette pairs early-onset psychosis with a congenital heart defect or cleft palate in a young person, the exam wants 22q11.2 deletion syndrome named as the underlying genetic risk factor, not a plain diagnosis of primary : it is the single strongest known chromosomal risk factor for psychosis, and missing that link is the most commonly tested trap in this whole topic.
Match each syndrome to its exact chromosome and its one standout feature: trisomy 21/18/13 by descending survivability, 47,XXY Klinefelter vs 45,X Turner, FMR1-repeat Fragile X, and 22q11.2 deletion as the strongest genetic risk factor for : then diagnose by karyotyping or targeted testing and manage each condition's psychiatric and physical features per NICE guidance.