Anatomical Clue to The Etiology of Epilepsy at Autopsy-Corpus Callosum Agenesis Associated with Willis Polygon Anomaly, Holoprosencephaly

In cases of infant deaths, distinguishing whether the death was due to natural causes is of paramount importance in forensic medicine. However, the inability to obtain medical records, insufficient information regarding the circumstances of death, and inadequacies in the scene investigation make this distinction challenging (6). This distinction is particularly crucial in cases of child deaths with a history of epilepsy. Given that mortality rates are found to be 2-5 times higher compared to the general population, forensic pathologists are likely to encounter early childhood death cases associated with epilepsy (7). Due to these challenges, evaluating the etiology of this disorder becomes difficult.

In cases of child deaths, physical abuse should always be suspected and ruled out. In cases of infant deaths, primary caregivers often cannot provide reliable information due to their emotional state, or no information can be obtained at all. In such situations, every finding in the postmortem examination and classical autopsy serves as an important clue. In our case, classical autopsy revealed that the anterior communicating artery was very thin, the posterior communicating artery was absent at the brain's base, and sections of the brain showed intermittent discontinuity of the corpus callosum.

In the literature, there are cases reporting that anomalies of the circle of Willis can be associated with holoprosencephaly (8, 9). Additionally, studies have documented the coexistence of cerebral artery anomalies identified through radiological examinations with agenesis of the corpus callosum (10). One case has reported that unilateral anterior cerebral artery anomalies were observed in conjunction with agenesis of the corpus callosum and epilepsy using radiological imaging (11). In our case, the combination of epilepsy and a history of seizures in the infant, along with anomalies of the circle of Willis and the corpus callosum, was directly observed through macroscopic examination in the classical autopsy.

Agenesis of the corpus callosum is reported as a rare congenital anomaly, typically inherited in an autosomal recessive, autosomal dominant, or X-linked manner. It is thought to result from an infection during pregnancy or from metabolic or mechanical effects during the second trimester that disrupt fetal brain development (12). Additionally, it has been noted that agenesis of the corpus callosum can occur in conjunction with holoprosencephaly (13-15). In our case, where agenesis of the corpus callosum and holoprosencephaly were observed together, it was found that the infant was the only child of the family, there was no known history of hereditary diseases among other individuals, including second and third-degree relatives, and no chromosomal anomalies were detected in the infant’s cytogenetic analysis.