Restless Legs Syndrome in NKX2-1-related chorea: An expansion of the disease spectrum

Abstract Background Molecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1 -related chorea, the clinical phenotype and sleep related disorders have been only partially characterized. Methods We propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires. Results In patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa. Conclusions Patients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.