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. 2018 Nov 9;6(1):34-39.
doi: 10.1002/mdc3.12690. eCollection 2019 Jan.

Is Benign Hereditary Chorea Really Benign? Brain-Lung-Thyroid Syndrome Caused by NKX2-1 Mutations

Mered Parnes  1   2 , Hassaan Bashir  2 , Joseph Jankovic  2
Affiliations

Is Benign Hereditary Chorea Really Benign? Brain-Lung-Thyroid Syndrome Caused by NKX2-1 Mutations

Mered Parnes et al. Mov Disord Clin Pract. .

Abstract

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.

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