Brainstem tegmental necrosis and olivary hypoplasia: a lethal entity associated with congenital apnea

Previously, we reported an isolated case of a newborn with central apnea at birth, ventilator-dependence, and combined malformative and destructive brainstem lesions (1). We now report 2 additional cases with similar clinicopathologic features. All 3 patients were male (XY karyotype) and required immediate ventilatory support in the delivery room. Perinatal complications included polyhydramnios and breech presentation. Variable cranial nerve palsies and orofacial and limb anomalies were present. The patients dies within minutes of withdrawal of ventilatory support at 2 to 11 weeks after birth. Significant neuropathologic findings were localized to the caudal pons and medulla, and included tegmental necrosis (neuronal loss, gliosis, mineralization) with involvement of respiratory-related nuclei, and anomalies of rhombic lip derivatives (olivary hypoplasia, arcuate nucleus hyperplasia). Three-dimensional computer reconstructions facilitated clinicoanatomic correlations, and underscored the restriction of the lesions to pontine and medullary rhombomeres and rhombic lip. The histopathology of these cases suggests a malformative process occurring at the end of the first trimester (time of rhombic lip migrations), and a superimposed destructive process (tegmental necrosis) in the second half of gestation. Although the etiology is unknown, the segmental nature of the lesions suggests the possibility of an abnormality in homeobox gene regulation. These cases likely represent a distinct clinicopathologic entity that should be considered in the differential diagnosis of Moebius syndrome and failure to breathe at birth.