Interstitial lung diseases in children of genetic origin

Interstitial lung diseases in children of genetic origin. Interstitial lung disease (ILD) in children (chILD) encompasses a heterogeneous group of rare respiratory disorders, most of which are chronic and severe. In more and more of these cases, a genetic cause has been identified. As of now, the main mutations have been localized in the genes encoding the surfactant proteins (SP)-C (SFTPC), SP-B (SFTPB), their transporter ATP-binding cassette, family 1, member 3 (ABCA3), transcription factor NK2 homeobox 1 (NKX2-1) and, more rarely, SP-A1 (SFTPA1) or SP-A2 (SFTPA2). Pediatric pulmonary alveolar proteinosis (PAP) is associated with mutations in CSF2RA, CSF2RB, and MARS; more recently, mutations in STING1 and COPA have been associated with specific auto-inflammatory disorders including ILD manifestations. The relationships between the molecular abnormalities and the phenotypic expressions generally remain poorly understood. In the coming years, it is expected that newly identified molecular defects will help to more accurately predict disease courses and to produce individualized targeted therapies.