Genetic causes and clinical management of pediatric interstitial lung diseases
Nadia Nathan1,2, Keren Borensztajn2, Annick Clement1,2
1Service de pneumologie pédiatrique, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris (AP-HP), Centre national de référence des maladies respiratoires rares RespiRare.
Insights
Genetic factors significantly contribute to pediatric interstitial lung disease (chILD). Identifying molecular defects and genetic markers will improve disease prediction and personalized treatment strategies for chILD.
Area of Science:
- Pediatric Pulmonology
- Genetics
- Rare Diseases
Background:
- Pediatric interstitial lung disease (chILD) encompasses rare, chronic respiratory disorders with high morbidity and mortality.
- The pathogenesis of chILD is complex and involves significant genetic contributions.
- Current management strategies for chILD are largely empirical, often relying on corticosteroids.
Purpose of the Study:
- To provide updated information on molecular defects associated with the development of chILD.
- To review the genetic landscape of chILD and its implications for future therapies.
Main Methods:
- Literature review of genetic factors in chILD.
- Analysis of identified gene mutations and associated disorders.
- Discussion of emerging technologies in genetic research for chILD.
Main Results:
- Key mutations identified in surfactant genes (SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, NKX2-1).
- Mutations in CSF2RA, CSF2RB, MARS linked to pulmonary alveolar proteinosis.
- STING and COPA disorders implicated in specific auto-inflammatory forms of chILD.
- Genotype-phenotype correlations remain poorly understood.
Conclusions:
- Genetic factors are crucial in chILD pathogenesis.
- Advancements in technology will expand the understanding of chILD genetics.
- Newly identified molecular defects and markers are expected to aid in disease prediction and personalized therapy development.
Purpose Of Review:
Interstitial lung disease (ILD) in children (chILD) is an umbrella term for a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and implicates genetic contributors. The purpose of this review is to provide updated information on the molecular defects associated with the development of chILD.
Recent Findings:
Currently, the main mutations are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, and NKX2-1. In addition, pulmonary alveolar proteinosis is associated with mutations in CSF2RA, CSF2RB, and MARS, and specific auto-inflammatory forms of chILD implicate STING and COPA disorders. The relationships between the genetic defects and the disease expression remain poorly understood, with no genotype-phenotype correlations identified so far. Although targeted therapies are emerging, the management strategies are still largely empirical, relying mostly on corticosteroids.
Summary:
Genetic factors play an important role in chILD, and the ongoing development of novel technologies will rapidly broaden the genetic landscape of chILD. Therefore, in the coming years, it is expected that newly identified molecular defects and markers will help predicting disease courses and tailoring individual therapies.
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