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Simons VIP: Expanding the Characterization of 16p11.2 Deletion Syndrome

Friday, 3 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
E. Hanson1,2, L. Green-Snyder2, R. P. Goin-Kochel3, F. K. Miller2, J. E. Olson2, K. Porche2, A. V. Snow2 and R. Bernier4, (1)Harvard Medical School, Boston, MA, (2)Developmental Medicine, Boston Children's Hospital, Boston, MA, (3)Pediatrics, Psychology Section, Baylor College of Medicine, Houston, TX, (4)University of Washington, Seattle, WA

Twin and family studies suggest that genetic and/or epigenetic factors are important in the development of ASD, although it is also clear that these influences are complex.  Much past work in this field has been marred by inconsistent diagnostic methodology and poorly defined subject populations, which make it challenging to link particular genes to clinical subtypes. 

The 16p11.2 deletion is the most common genetic disorder associated with ASD.  While the exact incidence of ASD in individuals with 16p11.2 deletion is unknown, ASD and ASD-like features appear to be more prevalent in these individuals than in the general population (Fernandez et al. 2011, Hanson et al. 2010, Bijlsma et al. 2009).  Medical issues also have been reported to be higher than the general population (Shen et al. 2010, Shimojima et al. 2009).  In addition, there have been reports of neurological findings in these individuals (Horev et al. 2011).  The Simons VIP is continuing to build an understanding of the phenotype of this disorder by investigating over 100 individuals with this recurrent genetic disorder. 

Objectives: To expand the characterization of 16p11.2 deletion syndrome.

Methods: Subjects are recruited from across the United States through the Simons VIP Connect website, and travel to the clinical sites for a 2-3 day research visit.  All consenting participants with a documented deletion in 16p11.2 receive a comprehensive diagnostic assessment including an Autism Diagnostic Observation Schedule (ADOS), a Diagnostic Interview Schedule for Children (DISC), cognitive, language, behavioral and adaptive skills assessments.  The Autism Diagnostic Interview – Revised (ADI-R) is administered when appropriate.  Comprehensive medical history information is obtained from participant report, and is also extracted from medical records.

Results: To date, we have enrolled 67 individuals (from 63 families) with a 16p11.2 deletion, all of whom are included in this interim analysis.

Within the deletion sample, 38 probands (56.7%) were male.  Probands ranged in age from 20 months to 16 years, and had a mean IQ of 83.2 (SD = 16.5).  Fourteen (21%) individuals received a research diagnosis of an ASD. There appeared to be an emerging pattern on ADOS scores for some individuals without ASD to have difficulties with communication and stereotyped behaviors, but not with social skills. 

The most common diagnoses were Developmental Coordination Disorder (n = 35), Phonological Disorder (n = 33), Language Disorders (n =32), and ADHD (n = 15). There were also a number of individuals diagnosed with Intellectual Disability (n = 13), Enuresis (n = 13), Borderline Intellectual Functioning (n = 13), and Disruptive Behavior/ODD (n = 9).  Only 1 individual received no diagnosis at all.  Additional analyses will be conducted to look at specific symptom profiles and compare those profiles to individuals in the Simons Simplex Collection. 

Conclusions: Among individuals with a 16p11.2 deletion, co-morbid diagnoses were extremely common, with 66 (98.5%) participants receiving one or more diagnoses in addition to 16p11.2 deletion.  The majority of individuals have a language delay, motor deficits, and attention issues.  ASD diagnosis was significantly higher than in the general population.

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