Simons Variation in Individuals Project: Characterizing the Phenotype of 16p11.2 Deletion Syndrome

Background:  Twin and family studies suggest that genetic 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 making 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 appears to be more prevalent in these individuals than in the general population (Fernandez et al. 2011, Hanson et al. 2010).  The prevalence of medical problems, particularly obesity (Jaquemont et al. 2011) as well as neurological conditions (Horev et al. 2011) are also higher.  We are characterizing the phenotype of this disorder by studying over 100 individuals with this deletion.

Objectives:  To characterize the phenotype of 16p11.2 deletion syndrome.

Methods:  Subjects are recruited from across the United States through the Simons VIP Connect website.  All consenting participants with a documented deletion in 16p11.2 (29,557,497-30,107,356 bp) 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.  Parents are interviewed for medical history. The Autism Diagnostic Interview – Revised (ADI-R) is administered when SRS, SCQ or ADOS scores are elevated or there is a clinician concern for ASD.

Results:  To date, we have enrolled 67 individuals (from 56 families) with a 16p11.2 deletion.  The first 32 children are included in this interim analysis. Of these, 19 individuals (59%) are male.  Participants range in age from 2 to 15 years, and have a mean FSIQ of 79 (SD = 14.9).  Five individuals received a diagnosis of an ASD.  In addition, 14 participants met criteria for ASD on either ADOS or ADI, but not both measures, and so did not meet full study criteria for an ASD.  There appeared to be an emerging pattern on ADOS scores for some individuals to have difficulties with communication and to have stereotyped behaviors, but no limitations in social skills.  Another trend appears to be one of gaining skills with age and no longer meeting ASD diagnostic criteria later in life.  The most common diagnoses were Language Disorders (n = 22), Developmental Coordination Disorder (n = 15), Intellectual Disability (n = 6), and ADHD (n = 16).  Other diagnoses include Phonological Disorder, Anxiety Disorder, Tic Disorder, and behavioral/mood disorders.  Only 1 individual received no neurodevelopmental diagnosis at all.

Conclusions:  Among individuals with a 16p11.2 deletion, co-morbid diagnoses were extremely common, with 19 (59%) participants receiving one or more neurodevelopmental diagnoses.  The majority of individuals have language delay, motor deficits, and attention issues.  These individuals also frequently have a pattern of symptoms similar to but not always reaching threshold for a research diagnosis of ASD.  Further analysis will be conducted to ascertain more fully the phenotype of individuals with a 16p11.2 deletion.