Autism Symptomatology In Primary Agenesis of the Corpus Callosum

Background: The corpus callosum (CC) is one of several structures thought to feature abnormal long-range connectivity in autism, as borne out by decreased CC volume and decreased functional coupling between homotopic cortical regions in autism. Agenesis of the corpus callosum (AgCC) is a congenital condition in which the ~190 million callosal fibers that normally connect the cerebral hemispheres fail to develop, even though anterior, posterior, and subcortical commissures are generally intact. Primary AgCC is characterized by minimal additional neuropathology, and intelligence in the normal range. However, individuals with Primary AgCC exhibit localized deficits in non-literal language comprehension, humor, theory of mind, and social reasoning. These findings together with parent reports suggest that behavioral and cognitive impairments in people with AgCC may overlap with the profile of autism spectrum disorders, particularly with respect to impairments in social interaction and communication.

Objectives: To clarify the phenotypic overlap of AgCC and autism spectrum disorders (ASD).  As part of a larger research programme, our initial objective was to assess such overlap with a standardized direct observation measure, the Autism Diagnostic Observation Schedule (ADOS)

Methods: The ADOS (Module 4) was administered to 24 adolescents and adults with Primary AgCC (age range = 16 - 54, mean = 28.54, sd = 11.53).   Mean full-scale IQ was in the average range (range = 78 - 129, mean = 96.32, sd = 15.06), as were VIQ (mean = 99.11; sd =16.60) and PIQ (mean = 93.95; sd =17.08). The group included six individuals with partial AgCC and 10 females;     a total 14 participants were fully right-handed.

Results: 7 out of 24 of AgCC group met ADOS criteria for an autism spectrum disorder.   All of these seven individuals had complete AgCC. Of these seven, four met criteria for autism and three met ASD criteria.

Although the mean FSIQ was lower for AgCC subjects who met ASD criteria (range 77 - 113; mean = 93.60; sd =15.16) than those who did not (range = 78 - 129; mean = 97.80; sd =15.05), the ranges clearly overlapped and the group difference was not statistically significant (p > .5).  The same held true for VIQ & PIQ scores.

Of the 17 AgCC subjects who did not meet ASD criteria on the ADOS, 4 met ASD criteria on either the communication or social interaction domains, documenting social and/or communication difficulties even though they did not meet criteria for an ASD.

Conclusions: Our findings from the ADOS strongly suggest that a significant subset of individuals with Primary AgCC will exhibit behavioral symptoms consistent with an ASD. Of those who met ASD criteria on the ADOS, all had complete callosal agenesis.  Discussion will explore clinical implications of these findings and their support for the connectivity hypothesis of social deficits in autism.