Isolated Agenesis of the Splenium of the Corpus Callosum Associated With Autism Spectrum Disorder: A Rare and Clinically Relevant Association.

The corpus callosum (CC) is the largest structure of white matter, connecting the two cerebral hemispheres. Agenesis of the corpus callosum (AgCC) is a rare but well-recognized neurodevelopmental malformation. It can be caused by genetic and chromosomal anomalies, metabolic and toxic causes, intrauterine developmental disorders, hypoxic-ischemic insults, infections, and other causes. While attention deficit hyperactivity disorder (ADHD) is frequently associated with AgCC, there is also a significant and disproportionate prevalence of autism spectrum disorder (ASD) in these individuals compared to the general population. We report a rare case with isolated agenesis of the splenium of the corpus callosum associated with autism spectrum disorder in a high-functioning 21-year-old man, who was brought to the neurology clinic by his stepmother with severe sleep dysregulation, excessive daytime sleepiness, and progressively aggressive behavioral issues. It is noteworthy that his biological mother was diagnosed with ADHD and has a cocaine addiction. Laboratory findings were within normal limits, and non-contrast brain MRI showed CSF collection posterior to the third ventricle and congenital absence of the splenium of the corpus callosum, and polysomnography showed obstructive sleep apnea. The patient was treated with lisdexamfetamine and clonidine, showing improvement over time. Continuous positive airway pressure (CPAP) therapy led to marked improvement in sleep quality and daytime symptoms. This case highlights the potential mechanistic role of altered interhemispheric connectivity in ASD, a relatively underexplored area of the literature. Furthermore, it emphasizes the importance of individualized treatment as well as neuroimaging in atypical behavioral presentations. Further research is needed into the role of focal corpus callosum abnormalities in autism spectrum disorder (ASD).