Improving care for people with 22q11 deletion syndrome

About 22q11 deletion syndrome

Claudia: “22q11 deletion syndrome is a genetic disorder that affects slightly more than 1 in 2000 people. So it is not extremely rare, but the disease is not really known to the general public. The name 22q11 refers to the chromosome where the syndrome originates. 22 refers to chromosome 22 and q11 to the spot on this chromosome: locus q11. For people familiar with the condition, the name makes sense, but for others, it may sound unfamiliar.”

There are two variants of 22q11: people can have a deletion (in which case a piece of DNA is missing) or a duplication (where there is an extra piece of DNA at that location). Both variants lead to health issues. These include physical and mental problems: some individuals are born with a congenital heart defect or a cleft palate. At young age, there are often problems with the immune system, making them regularly ill and more susceptible to infections. Some patients have an intellectual disability and nearly all patients experience cognitive problems, for example with planning and organizing. On top of this, people with 22q11 have a significantly increased risk of developing psychosis. This occurs in approximately 30% of patients; far more than the 3% seen in the general population. People with 22q11 who develop psychosis also deteriorate more cognitively. I deal specifically with this combination in my research. 

What does 22q11 mean for the people it affects?

The syndrome has a major impact on the lives of patients and their families. In childhood, the physical problems in particular demand a lot of time and attention. In adulthood, the high risk of psychiatric disorders becomes more prominent. Many individuals are unable to live independently and require lifelong care.”

About the research

Claudia: "In my research, I examine cognitive functioning, psychosis, and their interaction. In general, I aim to map out how the condition progresses into adulthood. The picture is that people with the syndrome deteriorate cognitively. I ask myself: are we looking at degeneration or are they growing into deficits, a phenomenon that refers to deficits becoming more pronounced with aging and increasing demands from society.  I study this from neurobiological perspective: how does cognitive functioning work in the brain in individuals with these genetic variants? To investigate this, I use patient data from both my practice in ‘s Heeren Loo and the database of the Expertise Centre of Maastricht UMC+. This contains patient information collected through a series of computer-based tasks. Additionally, there is extensive data available from international research consortia, allowing us to work with a substantial research population—thousands of patients in total."

Chemistry in the brain

"Regarding psychosis, I want to understand whether the brains of those who develop psychosis differ from those who do not. I investigate this using 7 Tesla MRI scans at Scannexus, looking at different neurotransmitters, or messenger substances, in the brain. One of the substances we know plays an important role in psychosis is glutamate. The glutamate system involves the balance between glutamate (which activates brain cells) and GABA (which actually makes them slow down). We can determine the amount of glutamate and GABA and (thus) the imbalance between them with MRI. The research shows that this system works differently in people with 22q11. The beauty is that when you understand more about the chemistry in the brain and focus more on the substances, opportunities arise to influence the balance more directly with pharmacological interventions."

Research on medication

"What we also see in this group of patients is that they suffer more from the side effects of antipsychotic medication than other people with psychosis. Additionally, these medications appear to be less effective for them. This may be because certain missing genes on chromosome 22 that affect brain chemistry. Current antipsychotic drugs mainly target the dopamine system, but people with 22q11 are more sensitive to these drugs, leading to increased side effects. So research into medication that works better for them is important. We are currently testing a drug already on the market for ALS, which may help restore the balance between glutamate and GABA. We hope this treatment will help with psychotic symptoms and cognitive symptoms in people with 22q11."

About impact

Claudia: “The research I do can be directly applied in my practice with patients. I recently published a paper in which, for the first time, we accurately described the degree of intellectual disability in relation to the adaptive skills you need in everyday life in adulthood (such as self-care and communication). On those topics, we get a lot of questions from parents in our practice. They want to know what their child's future will be like. Through my research, I can provide information and help to arrange necessary support. Our research has also contributed to new treatment guidelines for healthcare professionals. This way, we translate scientific findings directly into improved patient care.

We are now in the final phase of our medication research. If the results are positive, patients can benefit immediately. For those who do not respond to standard antipsychotics, this experimental drug is already being prescribed in some cases, with promising outcomes.”

More knowledge about the brain and cognitive problems

"All in all, I believe that research into rare conditions like 22q11 is crucial. It teaches us a lot about how the functioning of the brain and how this is influenced by genetics. Learning more about this specific group, moreover, also generates knowledge that can help us better understand cognitive functioning in the general population. This is important as people keep getting older which is often accompanied by cognitive decline. For example, for Alzheimer's, we still lack effective treatments. The research we do on cognitive functioning and the mechanisms behind it also contributes to broader knowledge on cognition and other cognitive disorders. Additionally, it helps us better understand other psychiatric disorders. The ongoing medication research for example, if the results are positive, may also benefit psychotic patients without 22q11. Similarly, our findings will not only provide insight into the brains of 22q11 patients but also help us better understand psychosis in the general population. The same applies to Parkinson's: in recent years, we have discovered that people with 22q11 are also at increased risk of developing this disease at a relatively young age. Because of this, we collaborate extensively with other professionals studying brain function."

Better perspective

"Some of the research, like the MRI research, are long-term projects. These findings are not immediately translatable to patient care. Ultimately, that should give us insight into how the brain functions and how we can develop and tailor interventions which will allow us to give patients a better perspective; either through medication or by being able to support and treat them better. The key to helping this group lies in a combination of psychological treatment, practical support, and pharmacological interventions."

"One of the most rewarding aspects of this research is working with the patients. They are often highly motivated individuals who show great dedication and willingness to participate in research. It is truly a privilege to work with them. This research is incredibly rewarding.”

¹22q11 is also known as Shprintzen syndrome, DiGeorge syndrome, and velocardiofacial syndrome, but the preferred term is 22q11.

Text: Eline Dekker
Photo: Joey Roberts

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