Clinical Classification of Borderline Cases in the Family Study of Essential Tremor: An Analysis of Phenotypic Features

BACKGROUND: In genetic research on essential tremor (ET), certain individuals may be particularly challenging to categorize diagnostically. METHODS: In the Family Study of Essential Tremor (>200 enrollees), 28 participants with borderline clinical findings who did not meet strict criteria for ET were assigned final diagnoses of ET. We scrutinized the clinical features of these cases and the sensitivity/specificity of certain features that best separated them from 19 unaffected individuals. RESULTS: Borderline ET cases differed from unaffected individuals in eight features: total tremor score, at least one kinetic tremor rating ≥1.5, at least one kinetic tremor rating ≥1.5 in the dominant arm, tremor rating during spiral drawing ≥1.5, higher spiral axis score, head tremor, complaint of tremor, and comment on tremor by others. The combination of at least one kinetic tremor rating ≥1.5 in the dominant arm and the presence of at least three of the remaining seven features predicted the clinician-assigned diagnosis in 88.6% of borderline ET vs. unaffected individuals (sensitivity 84.6%, specificity 94.4%). DISCUSSION: In a family study, a small number of clinical features characterized borderline ET, and a particular combination of these separated the majority of these borderline cases from normals. These analyses may help researchers minimize diagnostic misclassification.