De novo TITF1 gene mutation causing Benign Hereditary Chorea with Hypothyroidism and Pituitary Mass

Benign hereditary chorea (BHC) is an autosomal dominant disorder of early onset characterised by non progressive choreic movements with normal cognitive function occasionally associated with hypothyroidism and respiratory problems. This condition is caused by mutations in TITF-1 gene (also known as NKX2.1), encoding the Thyroid Transcription Factor-1 The proband of the described family, affected with BHC, presented in infancy with delayed walking and ataxic features, then chorea and developed hypothyroidism at the age of 33. She never experienced any respiratory symptoms, and on imaging she was found to have a large cystic pituitary mass. Genetic testing showed that the proband carries a novel TITF-1 nonsense mutation. This mutation was transmitted to her affected child, which presented in infancy with delayed walking and mild non-progressive chorea. The genetic analysis of the whole family confirmed that the mutation arose de-novo in the proband. We discuss the effect of this new mutation and the phenotype heterogeneity of the disease