Social Communication Skills and Impairments in Children with Dup15q Syndrome: Is There a Distinctive Phenotype That May Inform Intervention Targets?

Background: Duplications on chromosome 15q11.2-13 are highly associated with autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy.  Most studies to date have focused on diagnostic categorization of this cohort rather than performing a deeper characterization of the social communication, cognitive, and language profiles of this high-risk cohort.

Objectives: To determine whether there are distinctive features of the social- communication deficits found in children with Dup15q mutations and, if so, whether these characteristics could guide more targeted interventions for this genetically-based subgroup within the autism spectrum. Our study is driven by the hypothesis that there will be a distinctive developmental phenotype in children with Dup15q syndrome that will vary in severity across mutation size and location, and that this phenotype will be defined by expressive language and motor impairment with relatively preserved non-verbal social abilities. Interventions that capitalize on these strengths may ultimately facilitate gains in social communication function in these children.

Methods: In this ongoing study, children ages 18 months to 10 years with Dup15q syndrome are recruited from the Dup15q Alliance registry as well as the national Dup15q clinics, and they undergo a comprehensive, developmentally informed clinical phenotyping battery. We compare cognition, expressive and receptive language, social communication, play, and motor ability in this cohort (both intersitial and isodicentric cases) to that of an age matched cohort of children with non-syndromic ASD drawn from several existing studies in our UCLA Center for Autism Research and Treatment (CART). Measures include: Autism Diagnostic Observation Schedule (ADOS), Mullen Scales of Early Learning and/or Stanford- Binet Intelligence Scales, Early Social Communication Scale (ESCS), the Vineland Adaptive Behavior Scales, and the Structured Play Assessment (SPA).

Results: 14 children with Dup15q syndrome have been recruited for the study. Age range is 22 to 94 months, 6 males . All have isodicentric 15q [idic(15)], all have global developmental delay and/or intellectual disability. 8 children had developmental levels appropriate for ADOS testing and all of these children (8/8) met criteria for ASD on the ADOS, 1/8 with mild-moderate severity and 7/8 with moderate-high severity. Common, consistent characteristics that distinguished this group from those with non-syndrome ASD included: Expressive language delays greater than receptive language delays, verbal IQ lower than nonverbal IQ, significant gross motor delays (>2 standard deviations from normal), consistent lack of eye contact and inability to initiate joint attention on the ADOS and ESCS, and consistent evidence of responseto joint attention on the ADOS and ESCS.

Conclusions: A distinctive social communication profile is emerging in children with Dup15q syndrome, with impairments in motor function, visual attention, and initiation of engagement that may prevent the development of appropriate language and social communication behaviors. Targets for intervention include expressive language, initiation of joint attention, and overall attention to social cues in the environment.