Behavioral characterization of dup15q syndrome: Toward meaningful endpoints for clinical trials.

TitleBehavioral characterization of dup15q syndrome: Toward meaningful endpoints for clinical trials.
Publication TypeJournal Article
Year of Publication2020
AuthorsDistefano C, Wilson RB, Hyde C, Cook EH, Thibert RL, Reiter LT, Vogel-Farley V, Hipp J, Jeste S
JournalAm J Med Genet A
Date Published2020 01
KeywordsAdolescent, Autism Spectrum Disorder, Child, Child, Preschool, Chromosome Aberrations, Chromosome Duplication, Chromosomes, Human, Pair 15, Cohort Studies, DNA Copy Number Variations, Epilepsy, Female, Humans, Intellectual Disability, Male, Pedigree

Duplication of 15q11.2-q13.1 (dup15q syndrome) is one of the most common copy number variations associated with autism spectrum disorders (ASD) and intellectual disability (ID). As with many neurogenetic conditions, accurate behavioral assessment is challenging due to the level of impairment and heterogeneity across individuals. Large-scale phenotyping studies are necessary to inform future clinical trials in this and similar ID syndromes. This study assessed developmental and behavioral characteristics in a large cohort of children with dup15q syndrome, and examined differences based on genetic subtype and epilepsy status. Participants included 62 children (2.5-18 years). Across individuals, there was a wide range of abilities. Although adaptive behavior was strongly associated with cognitive ability, adaptive abilities were higher than cognitive scores. Measures of ASD symptoms were associated with cognitive ability, while parent report of challenging behavior was not. Both genetic subtype and epilepsy were related to degree of impairment across cognitive, language, motor, and adaptive domains. Children with isodicentric duplications and epilepsy showed the greatest impairment, while children with interstitial duplications showed the least. On average, participants with epilepsy experienced seizures over 53% of their lives, and half of children with epilepsy had infantile spasms. Parents of children with isodicentric duplications reported more concerns regarding challenging behaviors. Future trials in ID syndromes should employ a flexible set of assessments, allowing each participant to receive assessments that capture their skills. Multiple sources of information should be considered, and the impact of language and cognitive ability should be taken into consideration when interpreting results.

Alternate JournalAm J Med Genet A
PubMed ID31654560
PubMed Central IDPMC7334030
Grant ListP50 HD055784 / HD / NICHD NIH HHS / United States
U54 HD087101 / HD / NICHD NIH HHS / United States
EPBA2201857 / / F. Hoffmann-La Roche / International
/ / Dup15q Alliance / International