Background: Since its localization to the NKX2-1 gene in 2002, the phenotype of the disorder historically called "benign hereditary chorea" has been expanding beyond chorea.
Methods: The phenomenology of movement disorders and other symptomatology associated with mutations in NKX2-1 were characterized after a detailed evaluation of consecutive patients evaluated in our clinic over the past 3 years.
Results: We studied 5 patients (3 females), ages 2 to 31 years, with confirmed pathogenic variants in NKX2-1. All patients exhibited chorea, gross motor delay, and gait impairment. Other symptoms included neonatal respiratory failure (n = 4), cognitive deficits (n = 3), hypothyroidism (n = 4), joint laxity (n = 2), myoclonus (n = 1), hypotonia (n = 3), and seizures (n = 1). Chorea often proved refractory to medical therapies.
Conclusions: The phenotype associated with pathogenic variants in NKX2-1 frequently includes disabling and often medically refractory neurological and non-neurological abnormalities. We therefore suggest that the term benign hereditary chorea be abandoned in favor of its genetic designation as NKX2-1-related disorder.
Keywords: NKX2‐1; TTF‐1; benign hereditary chorea; brain‐lung‐thyroid disorder; brain‐lung‐thyroid syndrome.