Familial idiopathic normal pressure hydrocephalus

• Familial subgroup of iNPH is introduced and characterized.
• 5% of iNPH-patients had shunt-operated relative(s).
• Risk of dementia may be increased in familial iNPH.

Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE ε4 genotype.This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH.