Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, 
respiratory distress syndrome, and benign hereditary chorea is caused by thyroid 
transcription factor 1 (NKX2-1/TTF1) mutations. We report the clinical and 
molecular characteristics of four cases presenting with primary hypothyroidism, 
respiratory distress, and neurological disorder. Two of the four patients 
presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 
[c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without 
any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this 
raises the possibility of mitochondrial mutations contributing to thyroid 
dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, 
and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for 
NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities 
will enable a unifying diagnosis and genetic counseling for the affected 
families. In addition, identification of an NKX2-1 defect would be helpful in 
allaying the concerns about inadequate thyroxine supplementation as the cause of 
neurological defects observed in some children with congenital hypothyroidism.