NKX2.1 encodes TTF-1, which is expressed in the thyroid gland, brain, and lung, and haploinsufficiency for NKX2.1 results in “brain-thyroid-lung” syndrome (MIM no. 610978) and benign familial chorea (MIM no. 118700).27‐29 Affected individuals have variable degrees of pulmonary disease, thyroid dysfunction, and neurologic abnormalities.20,29‐33 None of the affected individuals in this family had a history of thyroid disease or chorea. TTF-1 is a critical regulator of early lung development and cellular differentiation, and specifically regulates the expression of SP-B, SP-C, and ABCA3 as well as many other genes.15,16,34‐36 A spectrum of pulmonary phenotypes has been described due to NKX2.1 mutations and deletions, with presentations ranging from severe neonatal respiratory distress syndrome, ILD in older children and adults, and recurrent pulmonary infections.20 Lung pathology findings have included deficient lung alveolarization and changes consistent with surfactant dysfunction, and alterations in surfactant protein expression have been observed when suitable samples were available for analysis.20,31,32,37 NEHI, thus, represents a novel clinical and histologic phenotype not previously described in association with NKX2.1 mutations. However, the absence of NKX2.1 mutations in eight other individuals with NEHI suggests that NKX2.1 mutations are probably not the mechanism underlying most NEHI cases. We speculate that, instead, the gene or genes primarily responsible for NEHI are regulated by TTF-1.