Age-Related Trajectories of Autistic Traits in Children With Angelman Syndrome

Abstract

Angelman syndrome (AS) is a rare neurogenetic disorder. Previous studies indicate a high prevalence of autism spectrum disorder (ASD) with considerable variability. Little is known regarding the longitudinal trajectory of autistic traits. We aim to investigate autistic traits, the effect of age on these traits, and associated features in AS children. This (partly) longitudinal clinical record study at the ENCORE Expertise Center involved 107 AS children aged 2-18 with one (N = 107), two (N = 49), or three (N = 14) measurements. Autistic traits and sensory processing issues were assessed using various instruments, and DSM classifications were used descriptively. Covariates were genotype, gender, and epilepsy. Results indicate a high prevalence of autistic traits and sensory processing issues. Children with the deletion genotype exhibited more autistic traits. Autism Diagnostic Observation Schedule (ADOS) classifications indicated higher rates of ASD compared to clinician DSM classifications. Autistic traits generally remained stable over time, except that ADOS scores significantly decreased for children with the UBE3A mutation genotype, and in the social affect domain for the entire group. In conclusion, incorporating the assessment of autistic traits and sensory processing into clinical practice for AS is important to inform adaptations of the environment to meet the child's needs. Additionally, clinicians and researchers should be mindful of the potential for overestimating ASD traits in AS when relying on the ADOS. ASD diagnosis in AS should integrate multiple diagnostic instruments, diverse hetero-anamnestic sources, and multidisciplinary expert opinions.

Keywords: Angelman syndrome; Autism Spectrum Disorder; autistic traits; longitudinal; repeated measures; sensory processing.

FIGURE 1

Flow chart of the repeated measurements. The time between the visits is the average of all participants. ADOS = Autism diagnostic observation schedule; SRS = social responsiveness scale; SSP = short sensory profile.

FIGURE 2

Age‐related trajectories of ADOS total raw scores. Panel (A) shows a visual representation of the main effect of age on ADOS total raw score. Panel (B) shows the interaction effect between age and genotype on the ADOS total raw score. The black line in figure A represents the average ADOS total raw score over time (not corrected for covariates), with the gray band showing the 95% confidence interval. Higher scores reflect more autistic traits. All scores above the upper dashed line are classified by the ADOS as “autism,” all scores between the two dashed lines are “ASD,” and all points below the lower dashed line are “non‐spectrum.” These classifications are based on the algorithm for children with “little to no words,” which was used for approximately 90% of participants. ADOS = Autism diagnostic observation schedule; ICD = imprinting center defect; UPD = uniparental paternal disomy.

FIGURE 3

Age‐related trajectories of ADOS domain scores. Panel (A) shows the main effect of age on the ADOS social affect score, while Panel (B) displays the interaction effect between age and genotype on the ADOS social affect score. Panel (C) shows the main effect of age on the ADOS restricted/repetitive behavior score, and Panel (D) depicts the interaction between age and genotype on the ADOS restricted/repetitive behavior score. The black line in Figure A and C represents the mean ADOS scale scores over time (not corrected for covariates), with the gray band showing the 95% confidence interval. Higher scores indicate more autistic traits. ADOS = Autism diagnostic observation schedule; ICD = imprinting center defect; UPD = uniparental paternal disomy.

FIGURE 4

Age‐related trajectories of SRS total raw score. Panel (A) displays the main effect of age on SRS total raw score, Panel (B) shows the interaction between age and genotype on SRS total raw score, and Panel (C) depicts the interaction between age and gender on SRS total raw score. The black line in Figure (A) represents the average SRS total raw score over time (not corrected for covariates), with the gray band showing the 95% confidence interval. Higher scores indicate more autistic traits. ADOS = Autism diagnostic observation schedule; ICD = imprinting center defect; UPD = uniparental paternal disomy.

FIGURE 5

Age‐related trajectories of SSP raw total and subscales scores. The solid black line represents the mean SSP total raw score over time (not corrected for covariates), with the gray band showing the 95% confidence interval. Lower scores indicate more sensory processing problems. All scores below the dashed line are classified as “exceptionally low” in comparison to typically developing children (reference values of the SSP manual), indicating high sensory processing problems. ADOS = Autism diagnostic observation schedule; ICD = imprinting center defect; UPD = uniparental paternal disomy.