Pulmonary Hemorrhage in a Patient with Brain-Lung-Thyroid Syndrome Caused by a p.T86fs Variant in the NKX2-1 Gene

Abstract

Objective Brain-lung-thyroid syndrome is a rare disorder caused by mutations in the NKX2-1 gene. The syndrome is characterized by neonatal respiratory distress, choreoathetosis and hypothyroidism, but the clinical spectrum and severity of symptoms vary widely. To our knowledge, diffuse pulmonary hemorrhage has not been previously associated with the NKX2-1 gene. Case report We report a patient with brain-lung-thyroid syndrome who suffered from pulmonary hemorrhage in the third hour of life, which led to acute respiratory distress and required urgent endotracheal intubation and mechanical ventilation. In addition, our patient has a phenotype that is typical for brain-lung-thyroid syndrome and carries a de novo heterozygous pathogenic a p.T86fs variant in the NKX2-1 gene. Conclusion Pulmonary hemorrhage in our patient could be a primary manifestation of the brain-lung-thyroid syndrome. This report provides evidence of a wide spectrum of NKX2-1-associated pulmonary phenotypes and underscores the importance of considering NKX2-1-related disorder in the differential diagnosis of pulmonary disease of unknown cause.