Brain-lung-thyroid syndrome

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Classification according to ICD-10
E03.1 Congenital hypothyroidism without goiter
ICD-10 online (WHO version 2019)

The brain-lung-thyroid syndrome is a very rare congenital disease with the main characteristics congenital hypothyroidism , respiratory distress syndrome of the newborn and benign hereditary chorea .

Synonyms are: choreoathetosis-hypothyroidism-neonatal dyspnoea syndrome; English Brain-lung-thyroid syndrome; BLT syndrome; CAHTP; choreoathetosis, hypothyroidism, and neonatal respiratory distress; chreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction

The first description comes from the year 2002 by the neuropediatrist Heiko Kruge and coworkers and at the same time by Joachim Polenz and coworkers.

distribution

The frequency is given as less than 1 in 1,000,000, so far about 50 people have been reported. The inheritance is autosomal dominant .

root cause

The disease are mutations in NKX2-1 - gene on chromosome 14 locus q13.3 basis that the thyroidal transcription factor 1 coded.

Mutations in this gene are also held responsible for benign hereditary chorea and non- medullary thyroid cancer (NMTC).

Clinical manifestations

The clinical picture is very variable:

The full picture is found in around 50%, the lungs are not affected in 30%, and only 13% have benign hereditary chorea.

Changes in the thyroid gland manifest immediately after birth , albeit often only as a latent (subclinical) hypothyroidism. The lungs are also usually noticed as a respiratory distress syndrome. Neurological changes develop during the first year of life.

If there are large deletions on chromosome 14, further changes such as hypo- or oligodontia , microcephaly , failure to thrive , hypoparathyroidism can occur.

diagnosis

Often the newborn screening gives an initial indication. If there are additional neurological or pulmonary changes, an NKX2-1 defect must be considered. The detection of the mutation by human genetic testing ensures the diagnosis. By means of magnetic resonance imaging % abnormalities can be detected in the brain at about 20 microns.

Differential diagnosis

Other forms of congenital hypothyroidism, newborn respiratory distress syndrome and chorea must be differentiated.

therapy

Treatment consists of replacement therapy with thyroxine as early as possible.

Individual evidence

  1. ↑ a b c d e Brain-lung-thyroid syndrome. In: Orphanet (Rare Disease Database).
  2. ^ H. Krude, B. Schütz, H. Biebermann, A. von Moers, D. Schnabel, H. Neitzel, H. Tönnies, D. Weise, A. Lafferty, S. Schwarz, M. DeFelice, A. von Deimling , F. van Landeghem, R. DiLauro, A. Grüters: Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. In: The Journal of clinical investigation. Volume 109, number 4, February 2002, pp. 475-480, doi: 10.1172 / JCI14341 , PMID 11854319 , PMC 150790 (free full text).
  3. ↑ J. Pohlenz, A. Dumitrescu, D. Zundel, U. Martiné, W. Schönberger, E. Koo, RE Weiss, RN Cohen, S. Kimura, S. Refetoff: Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. In: The Journal of clinical investigation. Volume 109, number 4, February 2002, pp. 469-473, doi: 10.1172 / JCI14192 , PMID 11854318 , PMC 150877 (free full text).
  4. ↑ A. Carré, G. Szinnai, M. Castanet, p-Sura Trueba, E. Tron, I. Broutin-l'hermite, P. Barat, C. Goizet, D. Lacombe, ML Moutard, C. Raybaud, C. Raynaud-Ravni, S. Romana, H. Ythier, J. Léger, M. Polak: Five new TTF1 / NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. In: Human Molecular Genetics . Volume 18, Number 12, June 2009, pp. 2266-2276, doi: 10.1093 / hmg / ddp162 , PMID 19336474 .
  5. ↑ Choreoathetosis, hypothyroidism, and neonatal respiratory distress.  In: Online Mendelian Inheritance in Man . (English)
  6. ^ NK2 Homeobox 1.  In: Online Mendelian Inheritance in Man . (English)

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