Brain dysgenesis in Cornelia de Lange syndrome.

The neuropathological findings in a neonatal case of Cornelia de Lange syndrome (CDLS) were described. Two different types of lesions were revealed in the affected brain. The first type was classified as perinatal hypoxic-ischemic brain damage, associated with cyanotic congenital heart anomalies: subarachnoideal, intraventricular, and parenchymal hemorrhage, and multiple necrosis in the cerebral white matter, basal ganglia, internal capsule, thalamus, mammillary bodies and dentate nucleus. This type may be non-specific and common in premature babies dying soon after birth. On the other hand, the second type was classified as congenital dysgenesis of the brain: microbrachycephaly, immature or simple convolution pattern of the cerebral gyri, thickened leptomeninges, persistent subpial granule cells, hypoplasia of the anterior thalamic nuclei, neurohypophysis, lateral geniculate body, cerebral peduncle, ventral pons and cerebellar internal granular layer, and heterotopic cell nests in the cerebellar white matter. This type may indicate that the maturation of the brain can be disturbed in the fetal period, particularly in the mid-gestational period. In conclusion, pathognomonic or specific changes of CDLS might be absent in the brain. However, congenital dysgenesis of the brain, especially that found in the diencephalon and the cortico-ponto-cerebellar system, may constitute morphologic evidence explaining the severe growth retardation and neurological abnormalities in CDLS.