Background Angelman syndrome (AS) is a rare, neurodevelopmental disorder which presents itself with severe cognitive and physical developmental delay. AS is characterized by frequent laughing and...Show moreBackground Angelman syndrome (AS) is a rare, neurodevelopmental disorder which presents itself with severe cognitive and physical developmental delay. AS is characterized by frequent laughing and smiling, but recent evidence suggests that individuals with AS, especially those with non-deletion genotypes, may experience high levels of anxiety. The aim of the current study was to examine the influence of genotype on anxiety and emotional/behavioral problems in general in Angelman syndrome (AS), and to test whether relationships between genotype and anxiety or emotional/behavioral problems were mediated by cognitive developmental level. Methods For this purpose, 79 children with AS were included from a Dutch clinical record study. The children were separated into two groups according to genotype, namely the deletion and non-deletion group (predictor). The Bayley Scales of Infant Development-III NL cognition subscale was used to measure cognitive developmental levels (mediator) and the Child Behavior Checklist (CBCL) was used to measure anxiety and emotional/behavioral problems in general (outcome). The study is cross-sectional in nature. A mediation analysis was performed, including four linear regression analyses. Results Genotype did not significantly predict anxiety levels (π½ = .18, p = .117) or emotional/behavioral problems (π½ = .06, p = .589). Genotype significantly predicted cognitive developmental level (π½ = .63, p < .001), as children with a non-deletion had a higher cognitive developmental level than children with a deletion. Cognitive developmental level neither predicted anxiety (π½ = .16, p = .155) nor emotional/behavioral problems in general significantly (π½ = .07, p = .554). Genotype did not significantly predict anxiety (π½ = .13, p = .387) or emotional/behavioral problems (π½ = .05, p = .746) with cognitive developmental level taken into account. This indicates that cognitive developmental level does not mediate the relationship between genotype and anxiety or emotional/behavioral problems. Key conclusions In conclusion, the findings of the current study suggest that emotional/behavioral problems, and specifically anxiety, are not affected by genotype or cognitive developmental level in children with AS. Therefore, the mediation model was not found to be significant. These findings may be taken to indicate that attention should be given to children of both genotype subgroups in clinical practice.Show less
Angelman syndrome (AS) is a rare neurogenetic disorder characterized by, severe developmental delays, little to no speech development, seizures, gross and fine motor deficits, stereotypical...Show moreAngelman syndrome (AS) is a rare neurogenetic disorder characterized by, severe developmental delays, little to no speech development, seizures, gross and fine motor deficits, stereotypical behavior, and anxiety. There are four genetic subtypes of AS: deletion, UBE3A mutation, Paternal Uniparental Disomy (UPD), and Imprinting Defect (ID). Former research showed that there is a high comorbidity between AS and autism spectrum disorder (ASD). However, little is known about how autism symptoms develop over time in AS. This study aimed to investigate how the severity of autism symptoms develop over time for the total group of AS children, per genetic subtype, and per gender. The sample consists of 41 children with AS who were tested two to four times at the center of expertise in Rotterdam. The ages ranged between 2.7 and 18.6 years, and the average time between the first and last test date was 4.2 years. The severity of autism symptoms was measured with the Autism Diagnostic Observation Scale (ADOS). The course of autism symptoms over time was analyzed with a linear mixed effects model in R. Results indicated that the severity of symptoms does not change over time (p = .220). In addition, it was found that children with a deletion presented with more autism symptoms on baseline compared to the other genetic subtypes (for all comparisons the p-value was < .001). Longitudinally, we found that children with a deletion develop differently from children with UPD regarding the severity of autism symptoms (p = .012). Children with a deletion stay stable in the severity of autism symptoms over time whereas children with UPD decrease in the severity of autism symptoms. For gender, we found that boys present with more autism symptoms at baseline than girls (p = .046). Longitudinally, no differences were found in how boys and girls develop regarding the severity of autism symptoms (p = .356). This study was the very first to investigate how autism symptoms per genetic subtype and per gender develop over time in children with AS. The results will help to inform the clinicians and caregivers about the prognosis of autism symptoms in Angelman Syndrome.Show less
