One hundred family members of patients with 22q11.2 deletion syndrome and twenty healthcare professionals today upgraded their knowledge about the syndrome during a study day at UMC Utrecht, organized by the patient association Stichting Steun 22Q11. Among other things, they were informed about the latest research findings. In addition, common issues were addressed during workshops. As experts by experience, family members shared their questions, tips and tricks with each other, for example to combat sleep problems.
“Out of ten people with 22q11.2 deletion syndrome, five to seven have a congenital heart defect. Sometimes the situation is very serious and a child needs surgery or catheterization a few days after birth. In that case, it is ideal that both the Dutch reference center for this syndrome and a pediatric heart center are located at the Wilhelmina Children’s Hospital (WKZ). All the necessary knowledge and expertise is gathered here, so that the patient can be treated as quickly, properly and safely as possible.”
Speaking is Michiel Houben. The general pediatrician explains that patients with 22q11.2 deletion syndrome can also benefit later in life from the proximity of the pediatric heart center and the pooling of expertise. “An example: fifty percent develop a crooked back, scoliosis, at puberty and sometimes need surgery by an orthopedic surgeon for this. If a patient also has a severe heart defect, the expertise of a pediatric cardiothoracic anesthesiologist is essential. Who has experience not only with orthopedic problems, but also with children who have congenital heart defects.”
Don’t let Michael’s words give the impression that a congenital heart defect and scoliosis are the only symptoms of 22q11.2 deletion syndrome. Indeed, the syndrome is associated with as many as 180 symptoms. Palate, thyroid and parathyroid abnormalities are common, as are decreased resistance to infection, speech and language problems, low intelligence and psychiatric disorders such as ADHD, Autism Spectrum Disorder and schizophrenia. Some patients may have different symptoms than others, and their severity also varies.
Language researcher Tessel Boerma: “Some patients are in wheelchairs, others play sports at a high level. Some need specialized education, others can keep up in regular education. Although there is the same abnormality in the DNA, there are enormous individual differences.”
One in 2,000 to 3,000 Dutch people has 22q11.2 deletion syndrome. It is the second most common genetic syndrome after Down syndrome. Yet 22q11.2 is much less well known, in part because the symptoms are so diverse. Not every doctor thinks of the syndrome when a palate abnormality occurs, not every speech therapist or teacher takes 22q11.2 into account when there is a speech and/or language problem.
Michiel: “American research has shown that a patient visits an average of seven specialties before the diagnosis is made. We see it happen ourselves. As soon as we know that a child has the syndrome, we offer the parents to undergo a DNA test, because one in ten times the disease is transmitted from parent to child.” Tessel: “If the parent then indeed turns out to also have the syndrome, the puzzle pieces fall into place. Oh, that’s why I have such an extensive medical file. Or: Oh, that’s why I didn’t attend school.”
The cause of the syndrome is an abnormality on chromosome 22: a piece is missing there. In our country, all children with the disorder are preferably referred to the reference center at the WKZ. A wide range of health care providers follow nearly 600 patients. Michiel: “For regular check-ups they visit their hospital in their own region every year, for extensive check-ups they come to us on average every three years. In one part of the day, the patient is seen by as many medical specialists as possible who are knowledgeable about their – possible – symptoms.”
These include an ENT doctor, speech therapist and plastic surgeon, who together form the palate team. Also present are a psychologist and orthopedic surgeon. Michiel: “And I am the general pediatrician who normally sees the patient. It is very nice that since a few years a representative of the patients’ association Foundation Support 22Q11 is always present. He can contribute ideas and answer questions. After the half-day session, we discuss the joint recommendation with the parents and the patient. For example, the plastic surgeon can perform speech-improving surgery in some patients with a non-working palate so that a person no longer talks through their nose (hypernasality). And in many patients with speech problems, speech therapists transfer advice for intensive counseling to children’s own speech therapist.”
Regularly, healthcare providers at the WKZ meet to coordinate the best approach for a patient. Such multidisciplinary meetings also take place in the field of scientific research. Language researcher Tessel Boerma regularly exchanges ideas with medical specialists. She works within the Utrecht Institute of Linguistics OTS, called Institute for Language Sciences from 2023. This is the home of language research at Utrecht University.
Tessel: “With 22q11.2 deletion syndrome, the medical world has long focused on the heart, palate and speech and on the cognitive development of patients. Since 2018, in Utrecht, we also look at language development. For example, we observe children during play or we do a language test. From our own research and other studies, we now know that 95 percent of patients have speech and/or language problems and are under the treatment of a speech therapist. This makes this one of the most common features of the syndrome.”
She explains: “Children have difficulty expressing themselves through language. At an age when other children can say complete sentences, they often still speak in single words or say nothing at all. They also often do not understand well what others are saying. All of this has a great impact on their functioning, now and in the future.”
Is there a connection between language problems and other developments? The researchers are also asking themselves that question. Tessel: “Where do language problems come from, for example? Is there a connection to cognitive ability? And if a patient has language problems at a young age, is he or she more likely to develop schizophrenia later in life, for example?”
In the ideal situation, research provides knowledge to prevent problems and improve quality of life. Tessel: “Suppose we conclude that there is indeed a link between language problems and the development of psychotic disorders. Then you can monitor children with language problems extra carefully and offer intensive guidance, language therapy for example, with the aim of reducing the risk of those disorders.”
Preventive scenarios are also on Michiel’s mind with ánother research, which was made financially possible by Foundation Support 22Q11. The pediatrician presented brand-new results during the study day on Saturday, Nov. 26.
He explains: “In every patient with the 22q11.2 deletion syndrome, almost an equal piece of chromosome 22 is missing. Yet not everyone has the same symptoms and the severity also varies. What causes this variation? Our finding is that it is partly related to differences in the RNA, or molecule that plays an important role in regulating genes. In the future, we hope to be able to predict, partly based on a person’s RNA, whether he or she has an increased or decreased risk of developing certain symptoms. If there is an increased risk, you may then be able to try to inhibit that development with an intervention at an early stage.”
During the study day, colleagues from Maastricht UMC+ were also present, as well as doctors for the mentally disabled (Arts VG). In adult patients with 22q11.2 deletion syndrome, the Physician VG is often the lynchpin for medical care. Physician VG Erik Boot also spoke during the study day. He supervises adult patients with 22q11.2 syndrome at ‘s Heeren Loo. Michiel: “I hope that in the future more Doctors VG can be connected to hospitals, so that they can exercise their coordinating role there as well.”
Funds from Foundation Support 22Q11 have made a database and a free online course possible. This is what visitors to the study day – also organized by the patient association – learned. Michiel: “We have built a database in which all the characteristics of our patients can be collected, i.e. those involving all disciplines. With this, new research questions can be answered in the future.”
Postdoc and psychologist Ania Fiksinski developed the free online course . This is a so-called MOOC, a massive open online course. Michiel: “Very interesting and useful for family members and caregivers, but also for professionals in other sectors.”
Don’t overestimate anymore
Tessel, who chaired the day during the study day, explains, “Teachers, speech therapists and others often don’t know that someone has 22q11.2 syndrome or what it means. As a result, they can easily overestimate and overask a child, with drastic consequences. We want to change that by increasing knowledge about the syndrome and its symptoms. The slogan of the patient association is all-important: Unknown makes misunderstood.”
