Which disease features run in essential tremor families? A systematic review

Essential tremor is a common and highly heritable movement disorder. It is largely unknown, however, to what extent family members share overlapping symptoms. Such knowledge would be useful, as it may lead to the definition of familial essential tremor phenotypes, which will aid the ongoing search for genotypes. Also, this information can be used by clinicians in patient counselling. Therefore, we conducted a systematic review to provide an overview of the evidence on which essential tremor features run in families, to assess the literature's strengths and weaknesses, and to provide recommendations for future studies. PubMed was searched resulting in 460 titles: sixteen articles ultimately proved fit for inclusion. The results are represented in line with the Axis 1 classification of tremor as published in the latest Consensus Statement. In summary, we found varying levels of positive evidence for familial aggregation of age at onset, disease progression, alcohol responsiveness, parkinsonism and dystonia. Evidence on midline tremor was conflicting. The evidence on familial clustering was negative for cerebellar signs and action tremor asymmetry. Although the level of evidence is modest, it seems that some disease features are indeed familial, while other features are not. We discuss complicating factors, such as state-vs-trait dependency of characteristics, the place of familial dystonia, and the development of diagnostic criteria for essential tremor over time. In the future, comprehensive replication studies are needed, with the addition of several characteristics that have not been investigated so far, as the next step towards discovery of essential tremor phenotypes.