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

Abstract

Background: 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 vs. 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. Methods: Probands (n=84 [56 ET-plus and 28 ET]) and their first- and second-degree relatives (n=182 and 48) enrolled in a genetics study. Chi-squares and generalized estimating equations (GEE) tested associations between probands’ ET-plus status and the ET-plus status of their relatives. Results: Chi-squares 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, p>0.05. Restricting relatives to first-degree relatives similarly did not detect a significant association (p = 0.88). GEE yielded similar results (respective p’s = 0.39 and 0.81). Conclusion: 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.

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China

“…A recent neuropathological study indicated that there were no pathological differences in the cerebellar cortex between ET plus and ET patients [7,17]. Several studies have also supported the hypothesis that ET plus and ET may not represent distinct clinicopathological entities [17,[44][45][46]. Neurological soft signs observed in some ET plus patients could be the physiological effects of aging superimposed on a pure ET.…”

Global Epidemiology of Movement Disorders: Rare or Underdiagnosed?

“…85 Furthermore, there has been no observed familial aggregation of the ET versus ET-plus phenotype. 86 Additional studies will likely be needed to better understand whether such diagnostic separation is warranted.…”