Genetic Testing for Neonatal Respiratory Disease

Abstract

Genetic mechanisms are now recognized as rare causes of neonatal lung disease. Genes potentially responsible for neonatal lung disease include those encoding proteins important in surfactant function and metabolism, transcription factors important in lung development, proteins involved in ciliary assembly and function, and various other structural and immune regulation genes. The phenotypes of infants with genetic causes of neonatal lung disease may have some features that are difficult to distinguish clinically from more common, reversible causes of lung disease, and from each other. Multigene panels are now available that can allow for a specific diagnosis, providing important information for treatment and prognosis. This review discusses genes in which abnormalities are known to cause neonatal lung disease and their associated phenotypes, and advantages and limitations of genetic testing.

Keywords: interstitial lung disease; persistent pulmonary hypertension of the newborn; primary ciliary dyskinesia; pulmonary surfactant; respiratory distress syndrome.

Figure 1

Analysis of 463 infants with severe, diffuse neonatal lung disease, 1995–2016. Analyses were focused on surfactant-related genes. Complete analyses could not be performed on all subjects as the number of genes to be analyzed included in the consent evolved over time, and retrospective analyses for genes not included in more limited consents were not performed, or insufficient samples remained. A genetic mechanism was identified in 44% of subjects.