Neuropsychological Correlates of Cortical Miswiring: A Case Series in Corpus Callosum Dysgenesis

Abstract

Background: Corpus callosum dysgenesis (CCD) is a neurodevelopmental disorder characterised by the absence or incomplete development of the corpus callosum, the largest white matter tract connecting the two cerebral hemispheres. CCD can occur in isolation or in association with other abnormalities or clinical syndromes. The disorder has been associated with a continuum of developmental outcomes, from relatively asymptomatic to severe disability. Anecdotal reports of impaired social skills are a primary concern within this population and there is a high incidence of autism spectrum disorders. Individuals with CCD commonly have difficulty with tasks reliant on higher-order ‘executive’ skills associated with frontal lobe functions. Relatively little research has investigated the possible contribution of higher order cognitive and language processes to reported social dysfunction. Mutations in DCC may result in CCD and can present with or without mirror movement disorder, characterised by involuntary movements on one side of the body that mimic voluntary movements on the other. The neuropsychological outcomes of mutations in DCC are yet to be described.Aims: Study 1 aims to characterise cognitive and behavioural functioning in a case series of adults with CCD. Specifically, it aims to investigate the executive processes in cognition and language that may contribute to anecdotal reports of social dysfunction. Further, it examines the utility of an external prompt as a potential support mechanism in this population. Finally, Study 2 provides in depth cognitive and behavioural phenotyping of a family presenting with a rare DCC mutation resulting in congenital mirror movement disorder and/ or CCD.Method: In Study 1, 13 participants with CCD (7 male and 6 female, mean age = 37.15, age range 20-72 years) completed a battery of standardised and experimental neuropsychological measures. Results were compared to available published normative data or healthy age- and gender-matched control participants. CCD and control participants were also compared at the group level. In Study 2, a family comprised of a mother (aged 44 years), daughter (aged 12 years) and son (aged 10 years) presented with DCC mutations causing mirror movement disorder. In addition, the son had partial CCD. The family completed a similar battery of neuropsychological measures, with results compared to published normative data.Results: In Study 1, CCD participants’ cognitive profiles ranged from superior to severely impaired. Visual memory, praxic functioning, and executive functioning were most commonly compromised. To a lesser degree, attention, verbal memory, speed of processing, and social cognition were impacted. High levels of emotional symptomology were reported in the CCD sample. The CCD participants were reduced on all measures of generative fluency, across verbal and non-verbal domains, and spontaneous speech. The CCD group showed benefit from a goal, but only on the phonemic verbal fluency condition. With regards to the DCC family (Study 2), the son was found to be intellectually impaired, with deficits across multiple cognitive domains. His two family members generally performed satisfactorily, although they demonstrated select areas of weakness. All three family members had significantly reduced spontaneous speech. Conclusions: In Study 1, the neuropsychological profiles of a group of CCD participants indicates variable outcomes of this disorder. Individuals with CCD frequently demonstrate impairments in areas associated with higher-order executive skills, consistent with prior research in this population. Additionally, they present with reductions in idea generation across verbal and non-verbal modalities, with severity ranging from mild to profound. In the context of generally sound core language skills, the pattern of reductions in idea generation across modalities is suggestive of a subclinical form of frontal dynamic aphasia in those with CCD. These reductions may contribute to the social difficulties commonly reported in this population. The provision of external prompts shows modest promise as a supportive mechanism. In Study 2, the case study describes a family including an individual with quite severe consequences of a DCC mutation. The results indicate the presence of CCD is likely to be associated with more detrimental developmental outcomes.