Clinical Characteristics of Children with Dup15q Syndrome and Comorbid ASD

Friday, May 13, 2016: 5:30 PM-7:00 PM
Hall A (Baltimore Convention Center)
C. DiStefano1, C. Kasari2, S. Huberty3 and S. S. Jeste4, (1)Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, (2)University of California Los Angeles, Los Angeles, CA, (3)Psychiatry and Biobehavioral Sciences, UCLA Center for Autism Research and Treatment, Los Angeles, CA, (4)Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA

Duplication 15q syndrome (Dup15q), one of the most common genetic variants associated with Autism Spectrum Disorders (ASD) (Hogart et al., 2010), is characterized by intellectual disability (ID), hypotonia, motor delays, and social communication impairment (Battaglia et al., 2010).  Because most research has consisted of retrospective chart reviews or case studes, we lack in-depth information about clinical profiles of children with Dup15q syndrome, notably in comparison to children with non-syndromic ASD.  Improved characterization of genetic syndromes associated with ID and ASD can inform not only prognosis, but also treatment, leading to the discovery of targeted, mechanism-based interventions that may improve individual outcomes.   


Examine social-communication, adaptive and cognitive skills in children with Dup15q syndrome and compare these domains to chronological and mental age matched children with non-syndromic ASD. 


Participants included 13 children with Dup15q syndrome (22 months – 12 years) and 13 children with non-syndromic ASD, matched on chronological and mental age.  In the Dup15q group, 10 participants had isodicentric duplications and 4 had active epilepsy. Participants were assessed for verbal and non-verbal developmental quotient, ASD characteristics and adaptive behavior.  Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group (by duplication type and epilepsy status).


All Dup15q participants met criteria for ASD, but had significantly lower ASD severity scores (specifically on certain reciprocal social interaction items) than children in the ASD group (t=2.26, p=0.03).  Dup15q participants demonstrated significantly more impaired motor (t=5.9, p<0.001) and daily living skills (t=2.41, p=0.03), and with significantly correlated scores across domains.  In contrast, the ASD group showed scores that were largely independent of each other.  Within the Dup15q group, there were no significant differences by duplication type.  Participants with epilepsy were significantly more impaired than those without across all domains other than ASD severity (p-value range: <.001 - .03).  


All children with Dup15q syndrome met ADOS criteria for ASD, but showed relative strength in social interest with marked impairment in motor and daily living skills.  Research is currently underway using electroencephalography (EEG) to examine neural correlates of social interest and language processing in Dup15q syndome in order to inform our understanding of how these processes interact with ASD symptoms.  In the Dup15q group, motor skills were closely related to abiities across domains.  Although children with ASD often show relative strengths in motor ability compared with other deveopmental domains (Yang et al., 015), recent studies have demonstrated the importance of early motor ability in predicting outcomes in children later diagnosed with ASD (Gernsbacher et al., 2008; Estes et al., 2015).  Dup15q syndrome presents an ideal opportunity to examine developmental relationships between motor impairment and emerging ASD symptoms.  Intervention recommendations for children with Dup15q syndrome include aggressive epilepsy treatment, focus on motor skills, and engagement based therapy building on social interest to further develop social communication abilities.  Longitudinal research from early development is necessary to understand the temporal relationships between developmental domains, and multi-site studies will allow for larger sample sizes to examine subgroups with Dup15q syndrome.