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0:03
I'm going to show you a few examples from research to better
understand the clinical consequences of pleiotropy and co-morbidity.
0:14
I've been active in clinical research in patients with the 22q11.2 deletion.
It's one of those CNVs that are pathogenic, and they occur recurrently in the population.
It's a deletion of the long arm of chromosome 22,
and in the majority (about 85 per cent) it's what we call the 'typical' deletion,
it spans about three megabases and it affects about 40 genes.
The remaining 15 per cent of children have deletions that are somewhat
atypical, because they are mediated by other low-copy repeats (LCRs) in the region,
LCRs are the green boxes in the figure.
Individuals with the 22q deletion have typical features,
although often not so pronounced that you would pick them out in a crowd;
but if you have been able to see a few of them, you do recognize a pattern.
It's also a multi-system disorder,
meaning the deletion has consequences across many systems.
The most common features include congenital heart condition, cleft palate,
hypocalcemia, thymus aplasia, and a deficient immune response.
In addition to that, the brain is involved.
1:31
A typical trajectory for a patient with the 22q11.2 deletion would be, for instance,
the discovery of a congenital heart condition at birth,
and because of more and more routine genetic testing,
a genetic diagnosis of 22q deletion is made quite early in life, nowadays.
When the diagnosis of the 22q deletion is made,
we know at that particular moment that the child is at risk for
a range of other medical issues, the ones shown in my previous slide -
hypercalcemia, recurrent infections, and so on -
but I will zoom in here on the neurodevelopmental aspect.
At the moment of this genetic diagnosis,
even if it's (let's say) at two or three months old,
we can already tell the parents that there is an increased risk that the child may
have any of a few different neurodevelopmental disorders,
such as autism spectrum, ADHD, intellectual disability.
There's also an increased risk for anxiety, and ultimately, towards adulthood,
one in four individuals with the 22q deletion develop schizophrenia.
However, these are group observations.
The relevant questions for parents of this particular child are:
will my child get ASD?;
will my child require support for learning?;
will my child develop schizophrenia in early adulthood?
