| Autor: |
Katharina Schuetz, Axel Schmidt, Nicolaus Schwerk, Diane Renz, Benedicte Gerard, Elise Schaefer, Maria Cristina Antal, Sophia Peters, Matthias Griese, Christina Katharina Rapp, Hartmut Engels, Kirsten Cremer, Anke Katharina Bergmann, Gunnar Schmidt, Bernd Auber, Jan C. Kamp, Florian Laenger, Sandra von Hardenberg |
| Rok vydání: |
2023 |
| DOI: |
10.22541/au.168480547.77927589/v1 |
| Popis: |
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 as well as aplasia of lacrimal and salivary glands (ALSG). Previous studies indicate that pathogenic variants in FGF10 can cause lethal human developmental disorders of the lung, but reports on diffuse lung disease caused by pathogenic variants in the FGF10 gene are lacking. We describe four children with postnatal onset of severe diffuse lung disease and heterozygous variants in FGF10, each detected by whole exome or whole genome sequencing. 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 and one patient is alive at age of six years, but still symptomatic. One patient presented signs of severe dental caries suggestive for ALSG or LADD-syndrome. Histopathological analysis of lung biopies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to diffuse developmental disorders of the lung and early onset lung fibrosis. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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