Katharina Schutz, Axel Schmidt, Nicolaus Schwerk, Diane Miriam Renz, Benedicte Gerard, Elise Schaefer, Maria Cristina Antal, Sophia Peters, Matthias Griese, Christina K. Rapp, Hartmut Engels, Kristen Cremer, Anke Katharina Bergmann, Gunnar Schmidt, Bernd Auber, Jan C. Kamp, Florian Laenger, Sandra von Hardenberg
Hannover Medical School. School of Medicine, University Hospital Bonn and University of Bonn. German Center for Lung Research. Unité de génétique moléculaire, Nouvel Hôpital Civil and Hôpitaux Universitaires. Ludwig-Maximilians-University.
Germany and France
Pediatric Pulmonology
Pediatr Pulmonol 2023;
DOI: 10.1002/ppul.26627
Abstract
Introduction: Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands. Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking.
Methods: We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing.
Results: All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6 years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis.
Discussion: Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes