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.
While the exact incidence of ASD in individuals with 16p11.2 duplication is unknown, ASD and ASD-like features appear to be more prevalent in these individuals than in the general population. Increased incidence of ADHD has been reported in individuals with 16p11.2 duplication (Shinawi et al. 2009). There are also reports of increased incidence of psychiatric disorders, particularly schizophrenia (McCarthy et al. 2009, Levinson et al. 2011). In addition, there have been reports of specific neurological findings in these individuals (Horev et al. 2011, Bedoyan et al. 2010). The Simons VIP is continuing to define the 16p11.2 duplication phenotype by investigating over 100 individuals with this recurrent genetic disorder
Objectives: To expand the characterization of the 16p11.2 duplication 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 duplication in 16p11.2 receive a comprehensive diagnostic assessment including an Autism Diagnostic Observation Schedule (ADOS), a DISC (Diagnostic Interview Schedule for Children), 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 37 individuals (from 29 families) with a 16p11.2 duplication, all Pf whom are included in this interim analysis.
Within the duplication sample, 19 participants were male (51.4%). Probands ranged in age from 7 months to 15 years, and had a mean IQ of 74.0 (SD = 22.3). Four (11%) individuals received a diagnosis of an ASD.
The most common diagnoses were Developmental Coordination Disorder (n = 15), Language Disorders (n = 11), Phonological Disorder (n = 7) and Borderline Intellectual Functioning (n = 7). Other common diagnoses included Intellectual Disability (n = 7), and ADHD (n = 8). Only five individuals received no co-morbid diagnoses. 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 duplication, co-morbid diagnoses were extremely common, with 32 (86.5%) participants receiving one or more diagnoses in addition to 16p11.2 duplication. Several individuals had motor and/or language delays.