Genetic Risk Factors for Essential Tremor: A Review

Abstract

Highlights In the current review, we thoroughly reviewed 74 identified articles regarding genes and genetic loci that confer susceptibility to ET. Over 50 genes/genetic loci have been examined for possible association with ET, but consistent results failed to be reported raising the need for collaborative multiethnic studies. Background: Essential tremor (ET) is a common movement disorder, which is mainly characterized by bilateral tremor (postural and/or kinetic) in the upper limbs, with other parts of the body possibly involved. While the pathophysiology of ET is still unclear, there is accumulating evidence indicating that genetic variability may be heavily involved in ET pathogenesis. This review focuses on the role of genetic risk factors in ET susceptibility. Methods: The PubMed database was searched for articles written in English, for studies with humans with ET, controls without ET, and genetic variants. The terms "essential tremor" and "polymorphism" (as free words) were used during search. We also performed meta-analyses for the most examined genetic variants. Results: Seventy four articles concerning LINGO1,

Essential Tremor

“…Moreover, a homogeneous cohort would be ideal for studies exploring the genetic substrates of ET, which has remained a gray area, although a plethora of clinical and epidemiologic studies have reported autosomal dominant transmission of the disease in half of the patients. 5…”

“…Moreover, a homogeneous cohort would be ideal for studies exploring the genetic substrates of ET, which has remained a gray area, although a plethora of clinical and epidemiologic studies have reported autosomal dominant transmission of the disease in half of the patients. 5 Although the new classification is advantageous from a pure or isolated ET standpoint, the label ET plus has been the point of several scientific debates. 2,6 Because of the marked variability in disease progression and tremor characteristics, and due to the growing evidence for the existence of a repertoire of nonmotor symptoms, ET is now unequivocally recognized as a clinically heterogeneous disease or a family of diseases.…”

Whole-Genome Study of a Multigenerational Family with Essential Tremor

“…8 ET is often inherited in an autosomal dominant mode. 9 However, it remains unclear whether strong familial aggregation of ET is the result of a highly penetrant mutation or the combined action of several low-risk variants. Up to 50 genes/loci have been reported to be associated with ET 9 and some genes have been shown to produce a different phenotype in the same family, such as HTRA2 10 and TNR.…”

“…9 However, it remains unclear whether strong familial aggregation of ET is the result of a highly penetrant mutation or the combined action of several low-risk variants. Up to 50 genes/loci have been reported to be associated with ET 9 and some genes have been shown to produce a different phenotype in the same family, such as HTRA2 10 and TNR. 11,12 Very few studies have identified mutations segregating with ET-affected family members, most of which were not confirmed in other families.…”

“…11,12 Very few studies have identified mutations segregating with ET-affected family members, most of which were not confirmed in other families. 9 Poor replication of ET loci points to the high genetic heterogeneity of ET, and the continued investigation of kindreds with a strong aggregation of ET is important. Hence, we conducted a comprehensive genome-wide analysis of a large Canadian family affected by ET with mainly childhood onset.…”