NKX2-1 Associated Phenotypes in Six Pediatric Patients

Background: The gene NKX2-1 encodes the thyroid transcription factor 1 (TTF1) which is essential in early embryonic development of thyroid gland, lung, basal ganglia and hypothalamus. Mutations in NKX2-1 cause (1) Brain-Lung-Thyroid-Syndrome [OMIM #610978] and (2) Benign Hereditary Chorea [OMIM #118700]. About 100 cases of mutations in NKX2-1 are reported to date. .

Methods: Identification of patients with mutations in NKX2-1, which were under physician’s care at the Centre of Paediatrics and Adolescent Medicine at the Freiburg University Medical Centre over a 10 year period via chart review.

Results: From 2009 to 2019 mutations in NKX2-1 were diagnosed in 6 children (Sanger-sequencing in n = 5; genetic panel diagnostics in n = 1). Genetic work-up was initiated in all children because of a present movement disorder (dystonic n = 1; atactic n = 2; atactic-choreiform n = 3). An isolated benign hereditary chorea was diagnosed in 2 patients. Thyroid disease was present in the other 4 patients, whereas 2 of those had an additional pulmonary phenotype (Brain-Lung-Thyroid-Syndrome). The movement disorder shows a stable course in the adolescent patients.

Conclusions: NKX2-1 associated phenotypes should be considered in the diagnostic workup of isolated movement disorders. The determination of TSH-levels is a cheap and easily available instrument for identification of NKX2-1 associated phenotypes with involvement of thyroid gland. Early detection is essential for monitoring of possible associated complications, such as malignoma of thyroid gland or lung, or interstitial lung disease, which can occur already in young adult age.

No conflict of interest has been declared by the author(s).