Social-Communication and Restricted and Repetitive Behavior (RRB) Profiles in Children with Phelan-Mcdermid Syndrome Compared to Non-Syndromic Autism Spectrum Disorder (ASD)

Thursday, May 14, 2015: 5:30 PM-7:00 PM
Imperial Ballroom (Grand America Hotel)
L. V. Soorya1, C. Farmer2, L. Bush3, S. Youngkin1, A. Kolevzon4 and A. Thurm5, (1)Psychiatry, Rush University Medical Center, Chicago, IL, (2)NIH, Bethesda, MD, (3)Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, (4)Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, (5)Pediatrics & Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD
Background: Phelan-McDermid syndrome (PMS) is a genetic syndrome caused by mostly de novo chromosomal abnormalities in the terminal end of 22q that  includes the SHANK3 gene. Loss of SHANK3, either through deletion or mutation, results in a phenotype characterized by significant intellectual disability, severe speech delay, hypotonia, minor dysmorphic features, and autistic-like behaviors. PMS is described as a common genetic form of ASD, accounting for up to 1% of ASD cases, with features including poor eye contact, self-stimulation, and repetitive mannerisms. However, the specificity, type, and degree of ASD symptoms in PMS remain unclear.

Objectives: The purpose of this investigation is to examine overlap and differences in ASD phenotype between PMS and non-syndromic ASD and to inform measurement targets for intervention research in PMS and  ASD. 

Methods: We analyzed ASD symptom profiles in a prospectively recruited sample of (n=24) of children with PMS (age 1.7 to 8.4 years) and a convenience sample of non-syndromic children with ASD, intellectual disability (ID), and language delay (n=38, age 2.1-8.2 years). The comparison group was a subsample of a larger community-based study of autism, selected on chronological age and developmental quotient scores <45. Measures included the ADOSG/ADOS2, ADI-R, and developmental/behavioral assessments. Non-parametric tests (Mann-Whitney U) were conducted on demographic and domain scores on the ADOS and ADI-R. 

Results: Mean ADOS2 and ADI-R domain scores were in the ASD range for the PMS sample. Children with PMS did not differ on mean social-communication (or social affect) domain scores on the ADOS2 or ADI-R. However, subdomain analyses showed more severe communication impairments in PMS relative to non-syndromic ASD (ADOSG, communication domain).  Peer relationships were less impaired in PMS relative to non-syndromic ASD (ADI-R, A2). The RRB domain also differed significantly between groups with lower scores in PMS relative to non-syndromic ASD on the ADOS2. Domain analysis of ADI-R scores indicate the PMS group had significantly fewer lower-order repetitive behaviors (ADI-R, C3 & C4) and higher scores on encompassing preoccupations/circumscribed interests (ADI-R, C1).  

Conclusions: Results from our study are the first to characterize ASD features in PMS relative to non-syndromic ASD.  Findings are consistent with a growing body of literature indicating the overlap between ASD and the clinical features of PMS. Our findings suggest potential for a distinct RRB profile in PMS relative to non-syndromic ASD with ID.  Investigations of neurobehavioral profiles in PMS are needed to understand the unique behavioral phenotype associated with SHANK3 deficiency.

See more of: Genetics
See more of: Genetics