Holoprosencephaly and agenesis of the corpus callosum: frequency of associated malformations.

Abstract

Review of 28 autopsy cases of holoprosencephaly (HPE) and 50 cases of agenesis of corpus callosum (ACC) (16 complete and 34 partial) revealed a high incidence of associated abnormalities in both the CNS and other organs. Craniofacial dysplasias were present in 92.8% of the HPE and in 37.8% of the cases with ACC; most frequent were microcephaly, hypotelorism, hypertelorism, and cleft formations. Associated CNS malformations were present in 93% of the cases of HPE and in 88% of those with ACC. In HPE except for constant defects of the forebrain commissures, the most frequent anomalies are migration disorders (95%), displaced hippocampus (85%) and fusion of the basal ganglia (65%) not seen in “arhinencephaly” (olfactory aplasia without failure of prosencephalic cleavage) except for occasional synthalamus. Less frequent were hydrocephalus (61%), lobar hypoplasia, porencephaly, arachnoid cysts, vascular malformations, and dysraphic lesions. Associated anomalies in ACC are Probst's longitudinal bundle (64%), hydrocephalus (44%), microcephaly and dysgyrias (38% each), rhinencephalic defects (32%), absence of forebrain commissures and other dysraphic changes, lobar hypoplasias and arachnoid cysts (12% each), and rare instances of cerebellar and brainstem dysplasia, optic nerve and tract anomalies, encephalocele and choroid plexus lesions. Non-nervous system malformations include a wide variety of musculoskeletal defects (35.8 and 25%), genitourinary (32.1 and 22.7%), cardiovascular (28.5 and 20.5%), gastrointestinal (39.5 and 9.5%), and other organ abnormalities. Comparison of these observations with the data from the literature emphasize the heterogeneity of associated malformations in telencephalic midline defects which show no consistent pattern except for craniofacial anomalies, microcephaly, hydrocephalus, and frequent migration disorders of the CBS.