Health Conditions Related to Genetic Changes
Brain-lung-thyroid syndrome
At least 100 mutations in the NKX2-1 gene have been found to cause brain-lung-thyroid syndrome, which encompasses a group of conditions that affect the brain, lungs, and thyroid gland. About half of affected individuals have problems with all three organs, while others have problems with one or two of them. The most common features of this syndrome are benign hereditary chorea, which involves involuntary jerking movements (chorea) of the face, torso, and limbs and other uncontrolled movements; severe breathing difficulty (respiratory distress syndrome); and reduced thyroid gland function (hypothyroidism).
Many of the NKX2-1 gene mutations involved in brain-lung-thyroid syndrome result in an abnormally short homeobox protein Nkx-2.1 that cannot function normally. Other mutations change single protein building blocks (amino acids) in the protein, impairing its ability to attach to DNA. Still others delete the whole NKX2-1 gene. A shortage of functional homeobox protein Nkx-2.1 alters the expression of genes important for the normal development and functioning of the brain, lungs, and thyroid. The production of surfactant proteins is reduced, leading to breathing difficulty; expression of genes involved in the production of thyroid hormones is impaired, accounting for hypothyroidism; and brain development is impaired, likely due to improper interneuron formation or migration, which may underlie the movement abnormalities characteristic of brain-lung-thyroid syndrome.
More About This Health ConditionOther Names for This Gene
- BCH
- BHC
- homeobox protein NK-2 homolog A
- homeobox protein Nkx-2.1 isoform 1
- homeobox protein Nkx-2.1 isoform 2
- NK-2
- NK-2 homolog A
- NKX2.1
- NKX2A
- NMTC1
- T/EBP
- TEBP
- thyroid nuclear factor 1
- thyroid transcription factor 1
- thyroid-specific enhancer-binding protein
- TITF1
- TTF-1
- TTF1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Butt SJ, Sousa VH, Fuccillo MV, Hjerling-Leffler J, Miyoshi G, Kimura S, Fishell G. The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron. 2008 Sep 11;59(5):722-32. doi: 10.1016/j.neuron.2008.07.031. Citation on PubMed or Free article on PubMed Central
- Carre A, Szinnai G, Castanet M, Sura-Trueba S, Tron E, Broutin-L'Hermite I, Barat P, Goizet C, Lacombe D, Moutard ML, Raybaud C, Raynaud-Ravni C, Romana S, Ythier H, Leger J, Polak M. Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Hum Mol Genet. 2009 Jun 15;18(12):2266-76. doi: 10.1093/hmg/ddp162. Epub 2009 Mar 31. Citation on PubMed
- Guillot L, Carre A, Szinnai G, Castanet M, Tron E, Jaubert F, Broutin I, Counil F, Feldmann D, Clement A, Polak M, Epaud R. NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in "Brain-Lung-Thyroid Syndrome". Hum Mutat. 2010 Feb;31(2):E1146-62. doi: 10.1002/humu.21183. Citation on PubMed
- Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, Tonnies H, Weise D, Lafferty A, Schwarz S, DeFelice M, von Deimling A, van Landeghem F, DiLauro R, Gruters A. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J Clin Invest. 2002 Feb;109(4):475-80. doi: 10.1172/JCI14341. Citation on PubMed or Free article on PubMed Central
- Nettore IC, Mirra P, Ferrara AM, Sibilio A, Pagliara V, Kay CS, Lorenzoni PJ, Werneck LC, Bruck I, Dos Santos LH, Beguinot F, Salvatore D, Ungaro P, Fenzi G, Scola RH, Macchia PE. Identification and functional characterization of a novel mutation in the NKX2-1 gene: comparison with the data in the literature. Thyroid. 2013 Jun;23(6):675-82. doi: 10.1089/thy.2012.0267. Citation on PubMed
- Nobrega-Pereira S, Kessaris N, Du T, Kimura S, Anderson SA, Marin O. Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors. Neuron. 2008 Sep 11;59(5):733-45. doi: 10.1016/j.neuron.2008.07.024. Citation on PubMed or Free article on PubMed Central
- Shetty VB, Kiraly-Borri C, Lamont P, Bikker H, Choong CS. NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients. J Pediatr Endocrinol Metab. 2014 Mar;27(3-4):373-8. doi: 10.1515/jpem-2013-0109. Citation on PubMed
- Williamson S, Kirkpatrick M, Greene S, Goudie D. A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome. J Child Neurol. 2014 May;29(5):666-9. doi: 10.1177/0883073813518243. Epub 2014 Jan 21. Citation on PubMed
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