Genetic Testing Utilization in the U.S. Registry for Childhood Interstitial and Diffuse Lung Diseases

• Published in: Pediatric pulmonology Vol. 60; no. 4; pp. e71073 - n/a
• Main Authors: Voss, Laura A., Nevel, Rebekah J., Wambach, Jennifer A., Nogee, Lawrence M., Deterding, Robin R., Casey, Alicia M., O'Connor, Michael G., Craven, Daniel I., Taylor, Jane B., Deutsch, Gail H., Tam‐Williams, Jade B., Steffes, Lea C., Brennan, Steven K., Santiago, Maria T., Sadreameli, Sara C., Heras, Andrea F., Powers, Michael R., Popova, Antonia P., Bansal, Manvi, Hamvas, Aaron, Gower, William A., Urrego, Fernando, Young, Lisa R.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2025; John Wiley and Sons Inc
• Subjects: Adolescent; Child; Child, Preschool; childhood interstitial lung disease (chILD); Children & youth; Exome Sequencing - statistics & numerical data; Female; Genetic testing; Genetic Testing - statistics & numerical data; Humans; Infant; Lung diseases; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - genetics; Male; Original; rare lung diseases; Registries; United States; Whole genome sequencing; United States; United States > US; rare lung diseases; childhood interstitial lung disease (chILD); genetic testing
• ISSN: 8755-6863; 1099-0496; 1099-0496
• DOI: 10.1002/ppul.71073

ABSTRACT Introduction Childhood interstitial and diffuse lung diseases (chILD) comprise a diverse group of rare disorders. Identifying the underlying cause is crucial for treatment, prognosis, and estimating recurrence risk. The objective of this study was to assess the utilization of genetic testing for subjects enrolled in the United States National Registry for ChILD, a multicenter observational study. Methods Genetic data from participating sites were reviewed and analyzed in relationship to clinical characteristics. Results Of 609 children enrolled from 22 centers, genetic testing was performed for 55.5% (n = 338). Genetic testing results were positive (diagnostic) for 22.8% (n = 77), negative for 60.7% (n = 205), and uncertain for 16.6% (n = 56). Most testing was performed through gene panels (55.9%), followed by exome sequencing (ES) or whole genome sequencing (WGS) (26.9%), single gene testing (24.6%), and/or chromosomal microarray (11.8%). For participants with positive (diagnostic) genetic testing results, the majority were diagnosed through gene panel (33.8%; n = 26) or single gene testing (32.5%; n = 25). The most common diagnosis confirmed by genetic testing was SFTPC‐associated surfactant metabolism dysfunction. Of the 59 subjects with unclassified ILD, only 22% (n = 13) had undergone ES or WGS, 61% (n = 36) had received panel testing, and 27% (n = 16) did not have any genetic testing reported. Conclusion The utilization of genetic testing has been variable in infants and children enrolled in the ChILD Registry. Additional efforts are needed to develop genetic testing recommendations for children with suspected ILD. Furthermore, there is opportunity for broader utilization of ES/WGS and genetic discovery for children with lung disease of unclear etiology.