Exploring the Relationship Between Essential/Complex Autism Subgroups and Parent Report of ASD Phenotypic Variables

Background: Previous studies examining ASD heterogeneity have identified a subgroup of individuals, termed “Complex” autism.  These individuals, comprising about 20% of the ASD population, have been found to have lower IQs, more seizures, and more abnormalities on EEGs and MRIs, and are defined as being dysmorphic or microcephalic. The remaining 80% have been termed “Essential” autism, which is more heritable with higher sib recurrence rates and a higher male to female ratio.

Objectives: In addition to replicating prior work identifying the differences between Complex and Essential autism, a primary aim of this study is to examine the relationship between parent report of ASD features (i.e., ADI-R) and genotypic subtypes of Essential vs. Complex.

Methods:  A subsample of 389 participants who had completed a dysmorphology examination was selected from the total sample of 1888 children who had participated in the Simons Simplex Collection (SSC). The SSC is a North American multi-site, university-based research study that includes families with only one child with an ASD. Comparisons between the Complex and Essential autism participants were made across a number of demographic and phenotypic variables using chi-square and t-tests. Logistic regression was then used to examine whether specific variables were significantly related to an individual being classified as complex or essential autism.

Results: The majority of the participants were in the Essential group (84%). No overall group differences were found with respect to age, SES, ethnicity, sex ratio, autism severity (i.e., ADOS Calibrated Severity Scale), regressive onset, abnormal EEG or MRI, autism syndrome diagnoses, or parent report of ASD symptoms (i.e., ADI-R subscales). The groups differed significantly with respect to intellectual functioning, with the Complex group having lower overall IQs (FSIQ = 70.9) compared to the Essential group (FSIQ = 86.9). The groups also differed in adaptive skills, with the Complex group being slightly more impacted than the Essential (Vineland 2 ABC = 72.3 vs. 75.4). The Complex group had more than twice as many reported seizures (17.5% vs. 7.6%). Initial logistic regression indicated that FSIQ was the strongest predictor of Essential vs. Complex autism, with higher IQ predicting Essential autism. Autism severity was also significant with greater severity predicting Essential autism. When behavioral predictors alone were examined, FSIQ was again significant, with the addition of core ASD communication symptoms as reported by parents (i.e., ADI-R Communication subscale). When this scale was examined independently, the specific symptoms of pointing, chatting, and stereotyped/echolalic language were most predictive – with greater symptom severity associated with Essential autism.

Conclusions: Results generally supported prior conclusions regarding the differences between Essential and Complex autism subgroups, with the Complex group comprising 16% of the sample, lower IQs, and more seizures. This SSC sample excluded individuals with a family history of ASD, which may account for discrepancies from prior results, such as differences in sex ratios. Further results indicated a relationship between the subgroups and behavioral phenotypic information, suggesting that beyond IQ, ASD symptoms associated with core communication deficits were also significantly associated with Essential or Complex autism.