Brain-Thyroid-Lung syndrome: a patient with a severe multi-system disorder due to a de novo mutation in the thyroid transcription factor 1 gene.
A 23-year-old man was diagnosed with pulmonary alveolar proteinosis at the age of 11 months, and primary hypothyroidism gradually developed during infancy. He had delayed developmental milestones and severe hypotonia that evolved into non-progressive chorea during childhood. He died from large cell lung carcinoma at the age of 23 years. A de novo heterozygous insertion mutation 859-860insC in the TITF-1 gene was demonstrated.


CONCLUSIONS
TITF-1 gene mutations should be considered in paediatric and adult patients with unexplained (combinations of) chorea, mental retardation, primary hypothyroidism, and chronic lung disease. Introduction of a name for the disorder, e.g. Brain-Thyroid-Lung syndrome, would probably facilitate further recognition. Whether the TITF-1 gene mutation in this patient predisposed to the development of lung cancer remains speculative.
Willemsen
Michel A A P
MA
Department of Paediatric Neurology, University Medical Center Nijmegen, 9101, 6500 HB, Nijmegen, The Netherlands. m.willemsen@cukz.umcn.nl
Breedveld
Guido J
GJ
Wouda
Siep
S
Otten
Barto J
BJ
Yntema
Jan L
JL
Lammens
Martin
M
de Vries
Bert B A
BB
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D017809:Fatal Outcome; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics; D013577:Syndrome; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors