Lack of Familial Aggregation of the "Essential Tremor-Plus" Phenotype in Familial Essential Tremor

Diane S. Berry, Nora Hernandez, Lorraine N. Clark, Elan D. Louis

Research output: Contribution to journalArticlepeer-review


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 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. 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. χ2 and generalized estimating equations (GEE) tested associations between probands' ET-plus status and the ET-plus status of their relatives. Results: 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, 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.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
Issue number5
StatePublished - Nov 1 2022
Externally publishedYes


  • Clinical
  • Epidemiology
  • Essential tremor
  • Essential tremor-plus
  • Familial aggregation
  • Genetic epidemiology

ASJC Scopus subject areas

  • Epidemiology
  • Clinical Neurology


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