Genetic testing for inherited respiratory conditions in the newborns

15 Oct 2022 11:40 12:10

Introduction: Respiratory distress is common in term newborn infants. Persistence of hypoxia or respiratory distress by two weeks should make one consider the possible diagnosis of Children’s Interstitial Lung Disease (chILD). 

Objectives: To discuss the “when, why and what” of genetic testing in infants suspected of chILD through clinical vignettes. 

Discussion: a) Baby J was intubated for respiratory distress from day 2 of life. Childhood ILD was considered at day 26 of life when transferred to our care. Whole Exome Sequencing (WES) revealed that he had compound heterozygote variants of ABCA3 mutation. Although he was extubated at day 83 of life, he required high non-invasive respiratory support that was finally withdrawn at 11 months old. b) Baby N presented with respiratory distress from birth and was invasively ventilated from day 10 till day 35 of life. She also had congenital hypothyroidism. Initial genetic investigation (INVITAE) detected a pathogenic variant in the NKX2-1 gene. However, it also detected multiple other variants of unknown significance, including for CF and PCD. Finally, WES confirmed the diagnosis of TTF-1. This patient defaulted to treatment and eventually succumbed to her illness at one year of life. C) This is an infant who presented at 2 months old with chronic diarrhoea, severe failure-to-thrive and recurrent respiratory infections. Bronchoscopic alveolar lavage showed evidence of lipid-laden macrophage and periodic-acid Schiff positive. Lung biopsy showed a possible acquired form of pulmonary alveolar proteinosis possibly secondary to aspiration or macrophage dysfunction and suggested genetic testing. Unfortunately, genetic testing was not able to detect any abnormality. The patient finally succumbed to her illness at 1yr 8 mths old.

Conclusion: Genetic testing is essential in a child suspected of chILD. Although results may not be timely or positive, it is essential for both the clinician and parent.