Lack of Familial Aggregation of the “Essential Tremor-Plus” Phenotype in Familial Essential Tremor

Abstract

<b><i>Background:</i></b> Essential tremor (ET) is a highly prevalent neurological disease that frequently runs in families. A recent and controversial proposal is to separate ET patients into two distinct groups – ET versus ET-plus. If this were a valid construct, one would expect in familial aggregation studies to observe that ET-plus would cluster in some families yet be absent in others, rather than being randomly distributed across families. We examined whether there is evidence of familial aggregation of ET-plus. <b><i>Methods:</i></b> Probands (<i>n</i> = 84 [56 ET-plus and 28 ET]) and their first- and second-degree relatives (<i>n</i> = 182 and 48) enrolled in a genetics study. χ² and generalized estimating equations (GEE) tested associations between probands’ ET-plus status and the ET-plus status of their relatives. <b><i>Results:</i></b> χ² analyses revealed that ET-plus was no more prevalent in relatives of probands diagnosed with ET-plus than in relatives of probands diagnosed with ET, <i>p</i> &#x3e; 0.05. Restricting relatives to first-degree relatives similarly did not detect a significant association (<i>p</i> = 0.88). GEE yielded similar results (respective <i>p</i>’s = 0.39 and 0.81). <b><i>Conclusion:</i></b> The data demonstrate that ET-plus does not seem to aggregate in families. As such, they do not lend support to the notion that ET-plus is a valid biological construct.