BACKGROUND: Angelman syndrome (AS) is a neurogenetic disorder characterized by severe intellectual disability, lack of speech, and low threshold for laughter; it is considered a 'syndromic' form of autism spectrum disorder (ASD). Previous studies have indicated overlap of ASD and AS, primarily in individuals with larger (∼6 Mb) Class I deletions of chromosome 15q11-13. Questions remain regarding whether intellectual disability solely contributes to ASD features in AS and how ASD features in AS change over time. In this study, we used a dimensional approach to examine ASD symptom severity in individuals with AS Class I versus Class II deletions within the context of cognitive development over time. METHODS: A total of 17 participants with a larger, Class I deletion and 25 participants with a smaller Class II deletion (∼5 Mb) were enrolled (age range = 2-25 years; 5 years 5 months). Standardized measures of cognition, language, motor skills, adaptive skills, maladaptive behavior, autism, and sensory-seeking behaviors/aversions were given at baseline and after 12 months. RESULTS: Despite equivalent cognition and adaptive behavior, the results of repeated measures analyses of variance indicate that participants with Class I deletions have greater impairment in social affect (F = 8.65; p = .006) and more repetitive behaviors (F = 7.92; p = .008) compared to participants with Class II deletions. Although both groups improve in cognition over time, differences in ASD behaviors persist. CONCLUSIONS: Despite a lack of differences in cognition or adaptive behavior, individuals with Class I deletions have greater severity in ASD features and sensory aversions that remain over time. There are four genes (NIPA 1, NIPA 2, CYFIP1, and GCP5) missing in Class I and present in Class Il deletions, one or more of which may have a role in modifying the severity of social affect impairment, and level of restricted/repetitive behaviors in AS. Our results also suggest the utility of a dimensional, longitudinal approach to the assessment of ASD features in populations of individuals who are low functioning.
BACKGROUND:Angelman syndrome (AS) is a neurogenetic disorder characterized by severe intellectual disability, lack of speech, and low threshold for laughter; it is considered a 'syndromic' form of autism spectrum disorder (ASD). Previous studies have indicated overlap of ASD and AS, primarily in individuals with larger (∼6 Mb) Class I deletions of chromosome 15q11-13. Questions remain regarding whether intellectual disability solely contributes to ASD features in AS and how ASD features in AS change over time. In this study, we used a dimensional approach to examine ASD symptom severity in individuals with AS Class I versus Class II deletions within the context of cognitive development over time. METHODS: A total of 17 participants with a larger, Class I deletion and 25 participants with a smaller Class II deletion (∼5 Mb) were enrolled (age range = 2-25 years; 5 years 5 months). Standardized measures of cognition, language, motor skills, adaptive skills, maladaptive behavior, autism, and sensory-seeking behaviors/aversions were given at baseline and after 12 months. RESULTS: Despite equivalent cognition and adaptive behavior, the results of repeated measures analyses of variance indicate that participants with Class I deletions have greater impairment in social affect (F = 8.65; p = .006) and more repetitive behaviors (F = 7.92; p = .008) compared to participants with Class II deletions. Although both groups improve in cognition over time, differences in ASD behaviors persist. CONCLUSIONS: Despite a lack of differences in cognition or adaptive behavior, individuals with Class I deletions have greater severity in ASD features and sensory aversions that remain over time. There are four genes (NIPA 1, NIPA 2, CYFIP1, and GCP5) missing in Class I and present in Class Il deletions, one or more of which may have a role in modifying the severity of social affect impairment, and level of restricted/repetitive behaviors in AS. Our results also suggest the utility of a dimensional, longitudinal approach to the assessment of ASD features in populations of individuals who are low functioning.
Authors: Lynne M Bird; Wen-Hann Tan; Carlos A Bacino; Sarika U Peters; Steven A Skinner; Irina Anselm; Rene Barbieri-Welge; Astrid Bauer-Carlin; Jennifer K Gentile; Daniel G Glaze; Lucia T Horowitz; K Naga Mohan; Mark P Nespeca; Trilochan Sahoo; Dean Sarco; Susan E Waisbren; Arthur L Beaudet Journal: Am J Med Genet A Date: 2011-10-14 Impact factor: 2.802
Authors: Michael P Hong; Janna L Guilfoyle; Lindsey N Mooney; Logan K Wink; Ernest V Pedapati; Rebecca C Shaffer; John A Sweeney; Craig A Erickson Journal: Res Dev Disabil Date: 2017-07-24
Authors: Anne C Wheeler; Joanna Mussey; Adrienne Villagomez; Ellen Bishop; Melissa Raspa; Anne Edwards; James Bodfish; Carla Bann; Donald B Bailey Journal: J Autism Dev Disord Date: 2015-03
Authors: Anjali Sadhwani; Anne Wheeler; Lynne M Bird; Wen-Hann Tan; Angela Gwaltney; Sarika U Peters; Rene L Barbieri-Welge; Lucia T Horowitz; Lisa M Noll; Rachel J Hundley Journal: J Autism Dev Disord Date: 2021-01-30