Pontocerebellar hypoplasia: review of classification and genetics, and exclusion of several genes known to be important for cerebellar development

Abstract

The pontocerebellar hypoplasias are a heterogeneous group of rare and devastating conditions characterized by multiple structural abnormalities of the ventral pons, inferior olive, and cerebellum. Here, we briefly review these conditions and discuss genes recently discovered to be involved in pontocerebellar hypoplasia pathogenesis. We then present data that exclude several genes important for cerebellar development as causes of pontocerebellar hypoplasia-4 and pontocerebellar hypoplasia-5, and we demonstrate that not all cases of clinically defined pontocerebellar hypoplasia-4 result from mutations in TSEN54. We conclude that classification based on clinical, imaging, and neuropathological findings does not differentiate between pontocerebellar hypoplasia subtypes with different genetic causes.