New thesis provides insights on Long-Term Mental Health and Multimorbidity in 22q11.2 Deletion Syndrome (22q11.2DS)
New thesis published on 22q11.2 Deletion Syndrome
22q11.2 Deletion Syndrome (22q11.2DS) is a rare genetic disorder resulting from a missing segment of chromosome 22. As the most common microdeletion syndrome, it occurs in approximately 1 in 2,000–4,000 newborns. Due to limited awareness of the condition, the actual prevalence may be higher than currently reported. The syndrome affects multiple organ systems, leading to a range of physical, intellectual, and psychiatric challenges, with comorbidities being highly prevalent. Over the years, international research has shown that approximately 180 different symptoms have been found to be associated with this syndrome. Congenital abnormalities, including heart defects, palate malformations, and disruptions in hormonal and immune system function, are frequently observed. Additionally, developmental disorders such as autism, ADHD, and intellectual disabilities are common, along with an elevated risk of mental health conditions such as anxiety, depression, and schizophrenia.
A new thesis just published by the Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, at the University of Gothenburg provides a groundbreaking series of studies with fresh insights into the long-term mental health and medical challenges faced by individuals with 22q11.2 Deletion Syndrome. Spanning from childhood to adulthood, these studies explore everything from eye contact sensitivity and cognitive changes to psychiatric risks and physical health outcomes, highlighting the pressing need for multidisciplinary, lifelong support for affected individuals.
During her PhD journey, Lena Wallin, doctoral student and child and adolescent psychiatry aimed to investigate development and health in a group of 79 individuals from an original cohort of 100 individuals with 22q11.2 Deletion Syndrome, who have been followed longitudinally into adulthood. Participants, along with a parent, were invited to take part in the studies. A short summary of each study can be found below.
Study 1
The 22q11.2 Deletion Syndrome affects not only physical health but also cognitive and emotional functioning, significantly increasing the risk of psychiatric and behavioural issues. This longitudinal study followed 79 individuals aged 18 to 50 with 22q11.2 Deletion Syndrome, examining neurodevelopmental (NDD) and psychiatric disorders in adulthood, tracking the stability of childhood diagnoses over time, and exploring how clinical characteristics in childhood and adolescence relate to diagnostic outcomes later in life.
Using validated instruments developed by the GNC, such as the Autism Spectrum Screening Questionnaire (ASSQ) and the Five To Fifteen questionnaire (FTF) for cognitive, psychiatric, and global functional assessment within a comprehensive clinical evaluation, the study found that NDD diagnoses made in childhood remained stable into adulthood, though their prevalence increased at follow-up. Anxiety, mood, and psychotic disorders were common, with the majority of participants meeting the criteria for at least one psychiatric disorder. However, the study showed that the rate of psychotic disorders was notably lower than in many previous studies. Intellectual ability at the initial assessment (T1) was the primary factor linked to variations in functioning at follow-up.
These findings highlight the heightened risk of NDD and psychiatric disorders, along with cognitive impairment and declining global functioning over time. They underscore the importance of ongoing clinical follow-up to ensure appropriate support and promote overall well-being, as well as the need for further research into effective interventions and treatment strategies.
Study 2
Individuals with 22q11.2 Deletion Syndrome often experience varying levels of social difficulties, including differences in the way they visually process faces. This study set out to explore whether sensitivity to eye contact, as reported by individuals with 22q11.2 Deletion Syndrome themselves, might be connected to these challenges.
Study participants with confirmed 22q11.2 Deletion Syndrome were interviewed about their experiences with eye contact, including any discomfort they felt. Those who reported discomfort were also asked about the strategies they used to cope with it. In addition to these self-reports, their eye movements were tracked while they looked at emotional faces to examine how their gaze patterns compared to typical viewing behaviour.
The results showed that those who found eye contact uncomfortable tended to spend less time looking at the eyes of neutral faces. They also lacked the usual left visual field (LVF) bias, which suggests differences in how their brains process visual information. Furthermore, this group scored lower on a measure of everyday functioning, indicating that their eye contact sensitivity might be linked to broader challenges in daily life.
These findings highlight the importance of simply asking individuals with 22q11.2 Deletion Syndrome about their experiences with eye contact. Their firsthand reports, combined with eye-tracking data, offer valuable insight into how their face-processing system works and the specific difficulties they may encounter. Understanding these nuances can help shape better support strategies for those affected by the syndrome.
Study 3
22q11.2 Deletion Syndrome: cognitive, visuomotor and adaptive functioning followed longitudinally (submitted to journal)
This study followed individuals with 22q11.2 Deletion Syndrome over time to examine their cognitive, visuomotor, and adaptive functioning, as well as how these factors relate to the development of psychosis in adulthood. A group of 79 participants, originally part of a cohort of 100 individuals, were assessed between 1997 and 2006 (when they were between 1 and 35 years old) and then re-evaluated in 2017-2022, by which time they were aged 18-50.
Overall, Full-Scale Intelligence Quotient (FSIQ) remained stable at the group level, but females showed a significant decline in both FSIQ and Visuomotor Integration (Beery VMI) over time. More participants displayed an uneven IQ profile compared to the general population with similar IQ levels. In the subgroup of individuals who developed psychosis (n=8), both FSIQ and Verbal IQ (VIQ) declined. By the second assessment, many participants had moderate to severe impairments in adaptive functioning, as measured by the Global Assessment of Functioning (GAF) scale, with FSIQ from the initial assessment predicting their later GAF scores.
These findings highlight the importance of long-term monitoring, as intellectual functioning appeared stable for some but declined for others. The link between decreasing FSIQ—particularly VIQ—and psychosis suggests that cognitive changes could either signal or contribute to psychiatric risks in this population. Providing tailored support and timely interventions may be crucial in mitigating these challenges.
Study 4
Long-Term Health Outcomes in 22q11.2 Deletion Syndrome: A Focus on Adult Physical Disorders and Phenotypic Diversity (manuscript)
22q11.2 Deletion Syndrome is a complex condition that affects individuals in many ways, from congenital and neurodevelopmental disorders in early childhood to psychiatric and medical issues that arise later in life. A long-term study followed 79 individuals with 22q11.2 Deletion Syndrome into adulthood, exploring their physical health, access to medical care, and treatment experiences. The findings revealed high rates of physical conditions, including congenital malformations, autoimmune diseases, and hormonal disorders, with many individuals experiencing multiple health issues at once. While most had frequent interactions with healthcare providers, some lacked proper long-term follow-up, despite their significant medical and neurodevelopmental needs. Hyperprolinemia was observed in >50% of cases but showed no link to neurodevelopmental or psychiatric conditions. These results highlight the diverse and complex health challenges faced by adults with 22q11.2 Deletion Syndrome, emphasising the urgent need for coordinated, multidisciplinary care to ensure better long-term health outcomes.
Text by Anna Spyrou (Communications Officer)
Lena Wallin’s dissertation will take place 4th April 2025 and will be held in Swedish. All are welcome to attend.
To download a digital copy of the thesis entitled “Long-term Mental Health and Multimorbidity Outcomes in 22q11.2 Deletion Syndrome- A Comprehensive Study from Childhood to Adulthood.”
