Chorea due to TITF1/NKX2-1 mutation: phenotypical description and therapeutic response in a family

Introduction. Chorea due to a mutation in the TITF1 gene, which is also known as benign hereditary chorea, is an autosomal dominant disorder that usually begins before the age of 5 years. In most cases, the chorea tends to improve as the child gets older. It may be associated to hypothyroidism and respiratory problems, such as neonatal alveolar respiratory distress syndrome or interstitial disease, since TITF1 is a transcription factor that is essential for the development of the brain, thyroid gland and lung. Case reports. We report on the clinical phenotype of a family with chorea, in which two sisters presented congenital hypothyroidism and one of them also had alveolar respiratory distress syndrome. A mutation was detected in TITF1 (c.825delC) in both of them and clinical improvement was observed in the response to treatment with low doses of levodopa-carbidopa. Conclusions. Chorea due to mutation of TITF1 is an underdiagnosed cause of chorea in children. Since it is possible to conduct a genetic diagnosis, we believe that performing it is always indicated in dominant familial cases, bearing in mind the variable penetrance, as well as in patients who present concomitant involvement of the lungs or hypothyroidism. Occasionally, it may be recommendable in cases of chorea with an unknown causation, which will enable us to avoid other tests, give a non-degenerative prognosis, offer genetic counselling and carry out more guided and effective therapeutic trials. For the time being, levodopa seems to be the preferred symptomatic treatment.