In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are ... more In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are at an increased risk of developing severe psychiatric disorders. Various studies have focused on detecting risk factors, but until now protective factors are still understudied in 22q11.2DS. The current case–control study focuses on the role of resilience and quality of life (QoL) in young adults with 22q11.2DS and behavioural problems, in comparison with persons with an intellectual disability (ID) without a known genetic disorder. Self-report (and caregiver report) standardized questionnaires were used. Predictive general linear models were constructed to compare the resilience and quality of life across both groups (22q11.2DS vs ID-group) and to analyse the association between personal characteristics in both groups. Young adults with a 22q11.2DS show less resilience compared with both the general population norms and young adults with ID. Only a subscale of resilience (Acceptance of self and life) contributes to the reported level of QoL. Reported health problems are not related to resilience, but have an important effect on QoL. Our results suggest different factors are underlying resilience and the relation with QoL in 22q11.2DS and ID in general. These factors deserve more research and are important to take into account in clinical practice.
22q11.2 deletion syndrome (22q11.2DS) is characterized by high rates of psychotic disorders and i... more 22q11.2 deletion syndrome (22q11.2DS) is characterized by high rates of psychotic disorders and immune abnormalities. Blood brain barrier (BBB) permeability is known to be a risk factor for schizophrenia and immune aberrations.Objective: to evaluate the relationship between psychosis and BBB permeability in this population.Methods: we examined two biomarkers for BBB permeability, s100β and neuron-specific enolase (NSE), in 22q11.2DS individuals with/without psychosis.The first cohort of this Israeli-Belgium study was comprised of 20 22q11.2DS adults (30.58 ± 9.42 years) afflicted with a psychotic disorder, another group of 69 non-psychotic 22q11.2DS adults (23.42 ± 8.36 years), and 58 healthy controls (26.39 ± 7.77 years). A second cohort was comprised of 18 non-psychotic 22q11.2DS Israeli children (5.83 ± 1.55 years) and 14 healthy controls (5.34 ± 1.43years). NSE and s100β serum levels were detected in all participants.Results: Both factors were elevated in adults with 22q11.2DS compared to healthy controls, specifically in the non-psychotic sub-group. In contrast, there were no significant differences in their levels between the two groups of the pediatric cohort.Conclusions: Increased BBB permeability seems to be a trait of 22q11.2DS that evolves sometime in early adulthood. Our findings are in line with previous reports on non-syndromic schizophrenia, and suggest potential novel neural pathways to psychosis in 22q11.2DS.
BACKGROUND Individuals with Phelan-McDermid syndrome (PMS) are characterised by phenotypical trai... more BACKGROUND Individuals with Phelan-McDermid syndrome (PMS) are characterised by phenotypical traits that can be experienced as challenging by their environment. This study assessed parenting stress and Family Quality of Life (FQOL) in parents of individuals with PMS and identified potential contributing variables. METHOD Mothers (n = 14) and fathers (n = 13) of individuals with PMS (n = 14; 6 females, 8 males; age 2-37, M = 20, SD = 11.92) completed questionnaires on parenting stress, FQOL, adaptive behaviour and background characteristics. RESULTS Mothers and fathers experienced high, similar and related levels of parenting stress and FQOL satisfaction. Parenting stress and FQOL satisfaction were inversely related. High and low ratings were retrieved for subscales measuring feelings of parental role restriction and emotional well-being, respectively. The adaptive skills of the individuals with PMS were related to fathers' parenting stress and FQOL satisfaction. CONCLUSIONS Clin...
The purpose of this review is to summarize the literature on cognitive development, communication... more The purpose of this review is to summarize the literature on cognitive development, communication, behavioral or psychiatric aspects and parenting stress in Phelan-McDermid syndrome (PMS) and to discuss the clinical implications and recommendations of these summarized findings. PMS is often associated with severe communication impairments, behavioral or psychiatric problems, and regression. These challenges may adversely affect and impair the quality of life of the individual with PMS and his family.
In this case report, we present a paternal transmission of a classic 3 Mb 22q11.2 deletion syndro... more In this case report, we present a paternal transmission of a classic 3 Mb 22q11.2 deletion syndrome (22q11.2 DS) in a 3 generation family. In this family a young girl, her father, her uncle and her grandfather were diagnosed with this disorder. All carriers showed phenotypic expression, there were no unaffected siblings in the second or third generation. Presenting symptoms in the patient in first generation (grandfather) were psoriatic arthritis, thrombocytopenia and a right aortic arch. There was no intellectual disability. The second generation uncle was known with a severe intellectual disability, mild facial characteristics, a septal defect and a clubfoot, whereas the second generation father had a tetralogy of Fallot, no intellectual disability and minimal facial characteristics. The third generation daughter had a moderate intellectual disability, hypernasal speech, triphalangeal thumb, severe speech and language development delay, pronounced facial characteristics and a diag...
Information, sustainability indicators and efficient public services are a permanent challenge fo... more Information, sustainability indicators and efficient public services are a permanent challenge for cities concerned with citizens" quality of life and effective local government. The objective of this study is to assess the digital city projects in Chicago and Schaumburg (USA), using information, sustainability indicators and public services offered to citizens by the website. The research methodology consisted of case studies covering city hall, municipal departments, and other local governmental entities. The analysis and results show similarity in the typologies of information, sustainability indicators and public services but also large discrepancies in amount of service provided. The conclusion demonstrates the importance of making digital city projects a municipal priority, mainly by having their projects among the USA top 10. It resulted in benefits for citizens through access to information, sustainability indicators and public services offered by the city and can contribute with the challenging issues of sustainability of cities, governments and citizens, as a form of participation in the planning and sustainability management in cities.
22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and c... more 22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6–9 years), adolescents (10–17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but...
Results: PRS interacts with ELCs on case-control status, in the three independent samples from US... more Results: PRS interacts with ELCs on case-control status, in the three independent samples from USA (p= p=0.004), Italy (p=0.018) and Germany (p=0.018); in each sample the variance of schizophrenia explained by PRS is multiplicatively higher in the presence of a history of ELCs compared with the absence of such events. The relationship between genomic risk and ELCs is further replicated in the two independent samples of only cases from Germany (p=0.047) and Japan (p=0.044). The gene-set based on PRS loci interacting with ELCs is highly expressed in multiple placental tissues (p<0.001) and dynamically regulated in placental samples from complicated, in comparison with normal, pregnancies (p<0.05). These differences are significantly greater in placentae from male compared with female offspring (p<10-8). The interaction between PRS and ELCs is largely driven by PlacPRS genes (p=0.002); PRS constructed from the remaining loci do not interact with ELCs (NonPlacPRS, p=0.60). Pathways and biological functions associated with NonPlacPRS genes are reminiscent of previous analyses about schizophrenia risk-genes, while PlacPRS genes implicate an orthogonal biology, with roots in the fetal/placental response to hypoxic stress. Discussion: Our data suggest that the most significant schizophrenia GWAS variants contribute to risk at least partly by converging on a developmental trajectory sensitive to ELCs and altered placental gene expression. The sexassociated effects on placental transcription suggest that the male preponderance of schizophrenia may arise from gene-environment interactions that influence placental biology. These results highlight placental health as a new public health frontier for primary prevention, particularly in highrisk males.
Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving ge... more Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The chromosome 22 LCRs (LCR22s) are amongst the most complex regions in the genome and their structure remains unresolved. These LCR22s mediate non-allelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS), causing the most frequent genomic disorder. Using fiber FISH optical mapping, we have de novo assembled the LCR22s in 33 cell lines. We observed a high level of variation in LCR22 structures, including 26 different haplotypes of LCR22A with alleles ranging from 250 Kb to over 2,000 Kb. An additional four haplotypes were detected using Bionano mapping. Further, Bionano maps generated from 154 individuals from different populations suggested significantly different LCR22 haplotype frequencies between populations. Furthermore, haplotype analysis in nine 22q11DS patients resulted in the localization of the NAHR site to a 160 Kb paralog between LCR22A and-D in seven patients and to a 31 Kb region in two individuals with a rearrangement between LCR22A and-B.. This 31 Kb region contains a palindromic AT-rich repeat known to be a driver of chromosomal rearrangements. Our study highlights an unprecedented level of polymorphism in the structure of LCR22s, which are likely still evolving. We present the most comprehensive map of LCR22 variation to date, paving the way towards investigating the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability in 22q11DS patients as well as in the general population.
In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are ... more In the transition period between adolescence and young adulthood, individuals with 22q11.2DS are at an increased risk of developing severe psychiatric disorders. Various studies have focused on detecting risk factors, but until now protective factors are still understudied in 22q11.2DS. The current case–control study focuses on the role of resilience and quality of life (QoL) in young adults with 22q11.2DS and behavioural problems, in comparison with persons with an intellectual disability (ID) without a known genetic disorder. Self-report (and caregiver report) standardized questionnaires were used. Predictive general linear models were constructed to compare the resilience and quality of life across both groups (22q11.2DS vs ID-group) and to analyse the association between personal characteristics in both groups. Young adults with a 22q11.2DS show less resilience compared with both the general population norms and young adults with ID. Only a subscale of resilience (Acceptance of self and life) contributes to the reported level of QoL. Reported health problems are not related to resilience, but have an important effect on QoL. Our results suggest different factors are underlying resilience and the relation with QoL in 22q11.2DS and ID in general. These factors deserve more research and are important to take into account in clinical practice.
22q11.2 deletion syndrome (22q11.2DS) is characterized by high rates of psychotic disorders and i... more 22q11.2 deletion syndrome (22q11.2DS) is characterized by high rates of psychotic disorders and immune abnormalities. Blood brain barrier (BBB) permeability is known to be a risk factor for schizophrenia and immune aberrations.Objective: to evaluate the relationship between psychosis and BBB permeability in this population.Methods: we examined two biomarkers for BBB permeability, s100β and neuron-specific enolase (NSE), in 22q11.2DS individuals with/without psychosis.The first cohort of this Israeli-Belgium study was comprised of 20 22q11.2DS adults (30.58 ± 9.42 years) afflicted with a psychotic disorder, another group of 69 non-psychotic 22q11.2DS adults (23.42 ± 8.36 years), and 58 healthy controls (26.39 ± 7.77 years). A second cohort was comprised of 18 non-psychotic 22q11.2DS Israeli children (5.83 ± 1.55 years) and 14 healthy controls (5.34 ± 1.43years). NSE and s100β serum levels were detected in all participants.Results: Both factors were elevated in adults with 22q11.2DS compared to healthy controls, specifically in the non-psychotic sub-group. In contrast, there were no significant differences in their levels between the two groups of the pediatric cohort.Conclusions: Increased BBB permeability seems to be a trait of 22q11.2DS that evolves sometime in early adulthood. Our findings are in line with previous reports on non-syndromic schizophrenia, and suggest potential novel neural pathways to psychosis in 22q11.2DS.
BACKGROUND Individuals with Phelan-McDermid syndrome (PMS) are characterised by phenotypical trai... more BACKGROUND Individuals with Phelan-McDermid syndrome (PMS) are characterised by phenotypical traits that can be experienced as challenging by their environment. This study assessed parenting stress and Family Quality of Life (FQOL) in parents of individuals with PMS and identified potential contributing variables. METHOD Mothers (n = 14) and fathers (n = 13) of individuals with PMS (n = 14; 6 females, 8 males; age 2-37, M = 20, SD = 11.92) completed questionnaires on parenting stress, FQOL, adaptive behaviour and background characteristics. RESULTS Mothers and fathers experienced high, similar and related levels of parenting stress and FQOL satisfaction. Parenting stress and FQOL satisfaction were inversely related. High and low ratings were retrieved for subscales measuring feelings of parental role restriction and emotional well-being, respectively. The adaptive skills of the individuals with PMS were related to fathers' parenting stress and FQOL satisfaction. CONCLUSIONS Clin...
The purpose of this review is to summarize the literature on cognitive development, communication... more The purpose of this review is to summarize the literature on cognitive development, communication, behavioral or psychiatric aspects and parenting stress in Phelan-McDermid syndrome (PMS) and to discuss the clinical implications and recommendations of these summarized findings. PMS is often associated with severe communication impairments, behavioral or psychiatric problems, and regression. These challenges may adversely affect and impair the quality of life of the individual with PMS and his family.
In this case report, we present a paternal transmission of a classic 3 Mb 22q11.2 deletion syndro... more In this case report, we present a paternal transmission of a classic 3 Mb 22q11.2 deletion syndrome (22q11.2 DS) in a 3 generation family. In this family a young girl, her father, her uncle and her grandfather were diagnosed with this disorder. All carriers showed phenotypic expression, there were no unaffected siblings in the second or third generation. Presenting symptoms in the patient in first generation (grandfather) were psoriatic arthritis, thrombocytopenia and a right aortic arch. There was no intellectual disability. The second generation uncle was known with a severe intellectual disability, mild facial characteristics, a septal defect and a clubfoot, whereas the second generation father had a tetralogy of Fallot, no intellectual disability and minimal facial characteristics. The third generation daughter had a moderate intellectual disability, hypernasal speech, triphalangeal thumb, severe speech and language development delay, pronounced facial characteristics and a diag...
Information, sustainability indicators and efficient public services are a permanent challenge fo... more Information, sustainability indicators and efficient public services are a permanent challenge for cities concerned with citizens" quality of life and effective local government. The objective of this study is to assess the digital city projects in Chicago and Schaumburg (USA), using information, sustainability indicators and public services offered to citizens by the website. The research methodology consisted of case studies covering city hall, municipal departments, and other local governmental entities. The analysis and results show similarity in the typologies of information, sustainability indicators and public services but also large discrepancies in amount of service provided. The conclusion demonstrates the importance of making digital city projects a municipal priority, mainly by having their projects among the USA top 10. It resulted in benefits for citizens through access to information, sustainability indicators and public services offered by the city and can contribute with the challenging issues of sustainability of cities, governments and citizens, as a form of participation in the planning and sustainability management in cities.
22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and c... more 22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6–9 years), adolescents (10–17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but...
Results: PRS interacts with ELCs on case-control status, in the three independent samples from US... more Results: PRS interacts with ELCs on case-control status, in the three independent samples from USA (p= p=0.004), Italy (p=0.018) and Germany (p=0.018); in each sample the variance of schizophrenia explained by PRS is multiplicatively higher in the presence of a history of ELCs compared with the absence of such events. The relationship between genomic risk and ELCs is further replicated in the two independent samples of only cases from Germany (p=0.047) and Japan (p=0.044). The gene-set based on PRS loci interacting with ELCs is highly expressed in multiple placental tissues (p<0.001) and dynamically regulated in placental samples from complicated, in comparison with normal, pregnancies (p<0.05). These differences are significantly greater in placentae from male compared with female offspring (p<10-8). The interaction between PRS and ELCs is largely driven by PlacPRS genes (p=0.002); PRS constructed from the remaining loci do not interact with ELCs (NonPlacPRS, p=0.60). Pathways and biological functions associated with NonPlacPRS genes are reminiscent of previous analyses about schizophrenia risk-genes, while PlacPRS genes implicate an orthogonal biology, with roots in the fetal/placental response to hypoxic stress. Discussion: Our data suggest that the most significant schizophrenia GWAS variants contribute to risk at least partly by converging on a developmental trajectory sensitive to ELCs and altered placental gene expression. The sexassociated effects on placental transcription suggest that the male preponderance of schizophrenia may arise from gene-environment interactions that influence placental biology. These results highlight placental health as a new public health frontier for primary prevention, particularly in highrisk males.
Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving ge... more Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The chromosome 22 LCRs (LCR22s) are amongst the most complex regions in the genome and their structure remains unresolved. These LCR22s mediate non-allelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS), causing the most frequent genomic disorder. Using fiber FISH optical mapping, we have de novo assembled the LCR22s in 33 cell lines. We observed a high level of variation in LCR22 structures, including 26 different haplotypes of LCR22A with alleles ranging from 250 Kb to over 2,000 Kb. An additional four haplotypes were detected using Bionano mapping. Further, Bionano maps generated from 154 individuals from different populations suggested significantly different LCR22 haplotype frequencies between populations. Furthermore, haplotype analysis in nine 22q11DS patients resulted in the localization of the NAHR site to a 160 Kb paralog between LCR22A and-D in seven patients and to a 31 Kb region in two individuals with a rearrangement between LCR22A and-B.. This 31 Kb region contains a palindromic AT-rich repeat known to be a driver of chromosomal rearrangements. Our study highlights an unprecedented level of polymorphism in the structure of LCR22s, which are likely still evolving. We present the most comprehensive map of LCR22 variation to date, paving the way towards investigating the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability in 22q11DS patients as well as in the general population.
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Papers by Elfi Vergaelen