Chapter 12 - Benign hereditary chorea

Abstract

Benign hereditary chorea (BHC) is a hyperkinetic movement disorder that historically has been characterized as a nonprogressive, dominantly inherited, childhood-onset chorea with normal intelligence. However, in some cases, atypical features were described such that controversy arose regarding whether BHC was a single syndrome. In 2002, a candidate gene, thyroid transcription factor (TITF-1), was identified to cause at least some cases of BHC. Since that time, the classical phenotype has expanded further to include "brain-thyroid-lung syndrome," which, in addition to the neurological symptoms, also manifests variable degrees of thyroid and lung abnormalities. Pathophysiologic mechanisms by which symptoms can occur are postulated to include haploinsufficiency (loss of function) and/or dominant negative effect on wild-type protein. However, genotype-phenotype correlations are complex and there is no clear relationship between mutation size, location or type of mutation, and severity of phenotype. Gross and microscopic pathology has been unremarkable, though immunohistochemistry suggests that BHC may manifest as a result of a reduced complement of migratory interneurons to the striatum and cortex. This chapter reviews the historical literature and current understanding regarding this familial, developmental disorder.