TY - JOUR T1 - Phenotype heterogeneity in a familial “brain lung thyroid syndrome” related to a novel <em>NKX-2.1</em> mutation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA3889 VL - 48 IS - suppl 60 SP - PA3889 AU - Nadia Nathan AU - Raphaël Borie AU - Sophie Jovien AU - Diane Doummar AU - Malek Louha AU - Julie Beucher AU - Mélanie Henriat AU - Estelle Breton AU - Annick Clement Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA3889.abstract N2 - 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&gt;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. ER -