Ciliogenesis Defect of Multiple Motile Cilia Causes Hydrocephalus

Hydrocephalus refers to a congenital or acquired accumulation of cerebrospinal fluid in the brain ventricles and affects approximately 1 in 1,000 newborn children. While some genetic causes have been elucidated during the last few years, there are many causes with unknown pathophysiological etiology.

Cilia are hairlike organelles protruding from the cell surface with different functions. While immotile primary cilia have mechanosensory functions, multiple motile cilia, covering specialized epithelia such as ependyma, respiratory tract, and fallopian tube, are beating vigorously to propel fluids along their surface.

Analysis of a cohort of individuals with mutations in the ciliogenesis of multiple motile cilia–associated gene MCIDAS revealed that seven of eight individuals (88%) present with known hydrocephalus.

Our analysis revealed MCIDAS as a new genetic cause for congenital hydrocephalus. While case reports had proposed a relationship between motile ciliary defects, we here for the first time show a clear association between hydrocephalus and a defect of multiple motile cilia.