Psychosis, short stature in benign hereditary chorea: a novel thyroid transcription factor-1 mutation

Benign hereditary chorea (BHC) is a rare autosomal dominant nonprogressive movement disorder. In some cases the phenotype includes, besides choreoathetosis, thyroid dysfunction and pulmonary infections in infancy, as expressed by the name "Brain-Thyroid-Lung syndrome". Mutations in the thyroid transcription factor-1 (TITF-1) gene have been identified in some BHC families. We present the phenotypic features of a family with chorea, hypothyroidism, and lung dysfunction. All affected individuals suffered from a nonprogressive chorea with infancy onset. All showed short stature and some webbed neck. One patient suffered from psychosis at the age of 27 years another from lung carcinoma. In all affected individuals, a novel mutation consisting of heterozygous C to A substitution at position 650 of the coding sequence of the TITF-1 gene, exon 3 was detected, leading to a premature stop at codon 217 (S217X). We describe the unique phenotypic features and intrafamilial variability expressing this novel mutation.