Heritable essential tremor-idiopathic normal pressure hydrocephalus (ETINPH).

摘要

In this report, we identified a large five-generation distinctive kindred with essential tremor (ET) presenting during the teen years and the consequent appearance of idiopathic normal pressure hydrocephalus (iNPH) when elderly (>65 years), in an autosomal dominant fashion. Through clinical and genetic analysis, we defined this kindred as a new essential tremor-idiopathic normal pressure hydrocephalus (ETINPH) disorder. One of the most common neurological disorders, ET comprises uncontrollable tremor, most commonly the upper limbs. Molecular genetic studies in hereditary ET have been initiated, but only with negative results so far. iNPH is an adult-onset hydrocephalus characterized by ventricular enlargement in the absence of significant elevations of intracranial pressure. iNPH patients usually have a triad of clinical symptoms: gait impairment, incontinence, and dementia, which is among the most common medical problems in the older population. The genetic etiology of iNPH is totally unknown. We hypothesize that ET is the consequence of the abnormal function of a specific neuronal gene, and that the same gene causes tremor at an early age eventually leading to the development of iNPH later in life. An understanding of the genetic components of this disorder may offer us significant insights into the molecular pathogenesis of ET, iNPH, and other related neurological conditions. In our genetic analysis of this family, array-based comparative genomic hybridization (aCGH) was carried out, and we could not identify any possible copy number changes of the genomic fragment along the whole-genome in ETINPH patient. Candidate gene linkage analysis was also performed, and we excluded this disorder from several established loci associated with tremor. We conclude that the pedigree reported here is a new autosomal dominant genetic disorder ETINPH. The characterization of the gene that causes ETINPH will certainly enhance our understanding of motor diseases in general.