Abstract
Background: The transcriptional factor NKX-2.1, also called TITF-1, has been shown to be involved in idiopathic interstitial pneumonias (IIP) pathophysiology. NKX-2.1 mutations are associated with a “brain-lung-thyroid syndrome”, but patients present with very heterogeneous phenotypes.
Objectives: We report a familial case of NKX-2.1 mutation involving a young infant and his mother.
Methods: The family was recruited through the French national network for rare lung diseases RespiFIL. A signed informed consent was obtained for each patient.
Results: A NKX-2.1mutation (c.373+2T>C, NM_003317.3) was identified in a full term new-born presenting with persistent hypoxia, peripheral hypothyroidism, and hypotonia. He displayed a severe IIP with diffuse ground-glass opacifications on the CT-scan. He was treated with intravenous corticosteroid pulses, oral azithromycin, and thyroid hormone supplements. His mother, aged 26, presented with abnormal moves since the age of 11, and a medical history of lung disease during childhood. So far, many investigations remained negative, and she had no respiratory complain. She was found to carry the same NKX-2.1 de novo mutation. Her respiratory investigations revealed a grade 2 dyspnoea and a lung fibrosis pattern on the CT-scan. She presented no thyroid dysfunction. An oral corticosteroid treatment was started.
Conclusion: A NKX-2.1 heterozygous mutation should be suggested in “brain-lung-thyroid syndrome”, but also in isolated paediatric and young adult cases of IIP, in the absence of documented causes. The familial screening can highlight a large spectrum of phenotypes, and allows patients to beneficiate from an early follow-up and treatment.
- Copyright ©the authors 2016
