The Pathophysiology of Lethality in Iniencephaly

Abstract

Iniencephaly is a rare and severe neural tube defect characterized by extreme retroflexion of the cervical spine and complex craniovertebral malformations. It is frequently considered a lethal condition due to its profound impact on central nervous system structures and the multiple associated anomalies. This article aims to review the pathophysiological mechanisms that explain the high mortality rate associated with iniencephaly and its prognosis.

The malformation originates during early embryogenesis, generally around the fourth week of gestation, due to failure of neural tube closure and abnormal development of the occipital bone and cervical vertebrae. The resulting craniovertebral malformation leads to severe distortion of the brainstem and upper cervical spinal cord, compromising essential neurorespiratory centers. In addition, thoracic deformities and restricted pulmonary development frequently result in pulmonary hypoplasia.

Neuropathological findings include abnormal curvature of the spinal cord, segmental compression, disorganization of neural tissue, and malformations of the bulbomedullary junction. Dysfunction of the brainstem and upper cervical spinal cord impairs respiratory control, particularly through involvement of the phrenic nerve (C3–C5), leading to respiratory failure and neonatal death. Although rare cases of prolonged survival have been reported, the prognosis remains extremely poor and depends mainly on the functional integrity of the brainstem and respiratory pathways.