Heritable essential tremor-idiopathic normal pressure hydrocephalus (ETINPH)

Area of Science:

• Neurogenetics
• Neurology
• Human Genetics

Background:

• Essential tremor (ET) is a common neurological disorder causing uncontrollable tremors, often in the upper limbs.
• Idiopathic normal pressure hydrocephalus (iNPH) is an adult-onset condition characterized by enlarged ventricles and a triad of gait impairment, incontinence, and dementia.
• The genetic basis for both ET and iNPH remains largely unknown.

Observation:

• A large, five-generation family exhibited an autosomal dominant inheritance pattern of early-onset essential tremor progressing to late-onset idiopathic normal pressure hydrocephalus.
• Clinical and genetic analyses were performed on affected individuals within the kindred.
• Genetic investigations, including array-based comparative genomic hybridization (aCGH) and candidate gene linkage analysis, did not reveal copy number changes or linkage to known tremor loci.

Findings:

• A novel autosomal dominant disorder, termed essential tremor-idiopathic normal pressure hydrocephalus (ETINPH), has been defined.
• The study excluded known genetic loci associated with tremor, suggesting a new genetic etiology.
• The identified kindred represents a unique model for studying the link between ET and iNPH.

Implications:

• Understanding the genetic underpinnings of ETINPH may provide crucial insights into the molecular pathogenesis of both essential tremor and idiopathic normal pressure hydrocephalus.
• This discovery could advance our comprehension of motor disorders and age-related neurological conditions.
• Further characterization of the causative gene for ETINPH is essential for elucidating its role in neurological disease.