Developmental and behavioral characteristics of children with Dup15q syndrome (P1.6-041)
Objective: To systematically assess developmental and behavioral characteristics in a large cohort of children with dup15q syndrome to identify clinical endpoints for future clinical trials.
Background: Duplication of 15q11.2–q13.1 (dup15q syndrome) is one of the most common copy number variations associated with autism and intellectual disability. As with many neurogenetic conditions, gathering accurate developmental and behavioral assessments is challenging. Large–scale phenotyping studies are necessary in order to inform participant selection and clinical endpoints for future clinical trials.
Design/Methods: Participants included 60 children with dup15q syndrome ages 30 months – 18 years, recruited from the national Dup15q Alliance, family meetings, and the UCLA Dup15q clinic. We evaluated multiple domains of development through both direct assessment and parent report, and we examined overall group phenotype as well as profiles based on duplication type and epilepsy status
Results: Children with isodicentric 15q duplication (idic15) and epilepsy showed the greatest level of impairment, while children with interstitial duplications (int15) showed the least. Three participants had developmental scores in the average range, while the remaining participants scored in the mild to severely impaired range. Adaptive behavior scores were significantly different across domains (F=14.69, p<.001). Communication domain scores were significantly lower than socialization (t=4.69, p<.001) and motor domains (t=3.18, p=.003), while daily living skills domain scores were significantly lower than socialization (t=3.19, p=.002) and motor domains (t=2.32, p=.03). Although adaptive behavior was strongly associated with cognitive ability, adaptive scores were higher on average than cognitive scores (t=11.73, p<.001). Measures of social communication were highly associated with developmental level.
Conclusions: Findings confirmed that both duplication type and epilepsy contribute to the level of impairment observed, although there is still substantial heterogeneity across individuals. Clinical trials in intellectual disability syndromes should employ a flexible set of assessments that allow each participant to receive the assessment that is the best fit for their skills
Disclosure: Dr. Distefano has nothing to disclose. Dr. Wilson has nothing to disclose. Dr. Jeste has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche Pharmaceuticals.