Neuropathology of Joubert Syndrome

Abstract

Very little documentation of the neuropathologic changes in Joubert syndrome exists. This paper presents a detailed postmortem neuropathologic study of a clinically and radiographically well-documented case of Joubert syndrome. In addition to aplasia of the cerebellar vermis and fragmentation of the dentate nuclei, there was marked dysplasia of structures at the pontomesencephalic junction and caudal medulla. There was abnormal decussation of the superior cerebellar peduncles and an enlarged iter (rostral 4th ventricle) with elongated tegmental nuclei (including the locus coeruleus). Neurons of the basis pontis and reticular formation appeared reduced. Extensive malformations of the medulla included hypoplasia of the inferior olivary nuclei, solitary nuclei and tracts, and the nucleus and spinal tracts of trigeminal nerve (cranial nerve V). Even more striking was dysplasia of the caudal medulla at the cervicomedullary junction, which was characterized by the absence of a posterior median sulcus, neuronal swelling and axonal spheroids in the region of malformed nuclei gracilis and cuneatus, and absence of pyramidal decussation. This study suggests that, in addition to vermal agenesis, Joubert syndrome is characterized by malformation of multiple brainstem structures. The latter could explain certain clinical features of the syndrome, including episodic hyperpnea and oculomotor apraxia. (J Child Neurol 1999;14:655-659).