Abstract: AbstractObjective: To summarize the clinical and genotypic features of 3 childhood interstitial lung disease（chILD）caused by SFTPC mutations with reduced penetrance. Methods: The clinical and genetic data of the 3 chILD patients caused by SFTPC mutations with reduced penetrance were analyzed. Literature on genotypes and phenotypes of chILD caused by SFTPC mutations were reviewed. Results: The three cases were full-term newborns with uneventfully delivery. They developed cough, tachypnea, cyanosis and continuous oxygen dependence during 2-15 months of age. One patient's brother has chILD consistent with SP-C (surfactant protein C) dysfunction. Pathogenic heterozygous missense mutations in SFTPC were detected in all 3 causes (c.218T>C, p.I73T, the most common SFTPC mutation reported, in 2 girls; c.314A>G, p.D105G, in a boy). There are healthy carriers in all 3 families which were found by pedigree validation. They are treated with mechanical ventilation, exogenous surfactant, steroid, and hydroxychloroquine. Conditions of 2 cases improved and 1 died respectively. There are 10 cases caused by SFTPC mutations with reduced penetrance reported in 7 literature with complete details. Altogether with the 3 cases in this study, chest CT of all 13 cases showed diffuse ground-glass changes and the onset ranged from birth to 11 years old. As for the outcomes, 2 cases died, 11 survived with chILD, and conditions of 9 improved. Conclusion: Reduced penetrance of chILD caused by SFTPC mutations also exists in Chinese Han population. Understanding of the clinical characteristics and genotypes of chILD contributes to early diagnosis, intervention, prognosis evaluation and genetic counseling.