title: Brain-lung-thyroid disease: clinical features of a kindred with a novel thyroid transcription factor 1 mutation.
abstract: Brain-lung-thyroid disease is a rare familial disorder caused by mutations in thyroid transcription factor 1, a gene that regulates neuronal migration. We report the clinical features of ten patients from a single family with a novel gene mutation, including observations regarding treatment. Neurologic features of the kindred included developmental delay, learning difficulties, psychosis, chorea, and dystonia. Three patients had a history of seizure, which has not been previously reported in genetically confirmed cases. Low-dose dopamine-receptor blocking drugs were poorly tolerated in 2 patients who received this therapy, levodopa improved chorea in 3 of 4 children, and diazepam was markedly effective in a single adult patient. Chorea related to brain-lung-thyroid disease appears to respond paradoxically to antidopaminergic drugs. The unusual therapeutic response seen in our patients and others may help elucidate how disease-related migratory deficits affect neural pathways associated with motor control.
authors.affiliation: Division of Movement Disorders, Department of Neurology, University of Louisville, Louisville, Kentucky, USA. ferrara.jay@gmail.com
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ferrara
authors.forename: Octavian R
authors.initials: OR
authors.lastname: Adam
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kirwin
authors.forename: David J
authors.initials: DJ
authors.lastname: Houghton
authors.forename: Casey
authors.initials: C
authors.lastname: Shepherd
authors.forename: Kathy M B
authors.initials: KM
authors.lastname: Vinette
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
mesh_terms: D000293:Adolescent; D000328:Adult; D001927:Brain Diseases / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013959:Thyroid Diseases / Q000150:complications / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors