Familial aggregation of idiopathic normal pressure hydrocephalus: novel familial case and a family study of the NPH triad in an iNPH patient cohort

Abstract

Objective: Idiopathic normal pressure hydrocephalus (iNPH) is considered sporadic, yet familial cases involving single pedigrees are being increasingly recognized. As current evidence does not extend beyond isolated pedigrees, we aimed to determine the putative heritability of iNPH by examining the prevalence of the iNPH triad among the family members of iNPH probands.

Method: We present a case-control family study of the iNPH symptom triad among the relatives of iNPH patients (n=20) identified from a cohort of patients undergoing CSF diversion and matched comparison subjects (n=21). A total of 291 first-degree relatives from 41 families were characterized using semi-structured family history interviews. Independent from the family study, we present a novel well-characterized familial case of iNPH.

Results: ≥ 2 insidious, progressive and idiopathic iNPH symptoms were identified among first degree relatives in 6 iNPH pedigrees (2 multiply affected) and 1 control pedigree, with an incidence of 7.1% among iNPH relatives and 0.7% among control relatives (OR=11.53). Gait disturbance and memory impairment began at a younger age among the relatives of iNPH probands. Independent of our family study, we present a novel case report of a large iNPH pedigree with multiple affected relatives.

Interpretation: Our family study and novel familial case suggest familial aggregation of iNPH. A larger family study with full characterization of affected and unaffected relatives is warranted. Confirmation of heritability may allow identification of individuals at high-risk for iNPH, early intervention, and improved aetiological elucidation.