title: Benign hereditary chorea: an update.
abstract: Benign hereditary chorea (BHC, MIM 118700) is a rare autosomal dominant disorder manifesting with chorea in conjunction with hypothyroidism and respiratory problems, a triad also named "brain-lung-thyroid syndrome". BHC is characterized by childhood onset with minimal or no progression into adult life and normal cognitive function. The genetic basis of BHC has been partially resolved, when mutations in the TTF1 gene on chromosome 14q13 encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1 (also known as TITF1, TEBP or NKX2-1), belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis. Clinical evaluation of TTF1 gene mutations carrier patients exposed the involvement of each of the triad's components characterized by heterogeneity between index cases and even within families. This review highlights the current updates on expanded clinical aspects of BHC, imaging and treatment experience, its genetic markers, proposed molecular mechanisms, animal models and link to cancer.
authors.affiliation: Joseph Sagol Neuroscience Center, Department of Neurology, Sheba Medical Center, 52621 Tel Hashomer, Israel. inzelber@post.tau.ac.il
authors.forename: Rivka
authors.initials: R
authors.lastname: Inzelberg
authors.forename: Moran
authors.initials: M
authors.lastname: Weinberger
authors.forename: Eva
authors.initials: E
authors.lastname: Gak
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002819:Chorea / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D018832:Molecular Chaperones / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D000071876:Prostaglandin-E Synthases; D013961:Thyroid Gland / Q000473:pathology / Q000503:physiopathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C504003:TTF1 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C490849:PTGES3 protein, human; D000071876:Prostaglandin-E Synthases