iNPH—the mystery resolving

• Main Authors: Ville Leinonen, Teemu Kuulasmaa, Mikko Hiltunen
• Format: Article
• Language: English
• Published: Wiley 2021-03-01
• Series: EMBO Molecular Medicine
• Online Access: https://doi.org/10.15252/emmm.202013720

Idiopathic normal pressure hydrocephalus (iNPH) is characterized clinically by degradation of gait, cognition, and urinary continence. INPH is progressive (Andrén et al, 2014), still probably underdiagnosed (Williams et al, 2019) but potentially treatable by CSF diversion (Kazui et al, 2015). Familial aggregation is a strong indicator of genetic regulation in the disease process iNPH (Fig 1). Enlargement of brain ventricles is associated with failed cerebrospinal (CSF) homeostasis by so far mostly unknown mechanisms. A mutation of the cilia gene CFAP43 in iNPH family, confirmed by a knocked‐out mouse model (Morimoto et al, 2019), allelic variation of NME8 (Huovinen et al, 2017), a segmental copy number loss in SFMBT1 in selected iNPH patients (Sato et al, 2016), and current results by Yang et al (2021) indicate that cilia dysfunction is one of the key mechanisms behind iNPH.