Clinical characteristics of SFTPC gene mutations in children: a single-center experience.

Abstract

Background: In pulmonary surfactants, surfactant protein C (SP-C) plays a critical role in regulating surface tension at the air-liquid interface of alveoli, primarily due to its robust hydrophobic property. Genetic mutations in the SP-C gene can compromise its structural integrity, thereby impairing its functional efficiency in surface tension modulation.

Method: A retrospective analysis was performed on 11 pediatric patients harboring SP-C gene mutations who were admitted to our medical center between June 2014 and June 2024.

Results: 11 pediatric patients with heterozygous SFTPC gene mutations were identified at our center. The age of onset spanned from birth to 5 years 2 months. Genetic analysis revealed that 9 patients carried the same SFTPC gene mutation at c.218T > C (p.Ile73Thr). 1 case previously reported, had compound mutations in both NKX2-1 and SFTPC genes. 1 case was newly identified splicing variant (c.612 + 1G > T). Predominant clinical manifestations included dyspnea and respiratory failure. Chest imaging predominantly demonstrates interstitial lung diseases (ILDs). In treatment, besides oxygen support, 3 patients received hydroxychloroquine (Hch) and 7 cases were administered azithromycin for infection prophylaxis. All patients received low-dose methylprednisolone (1-2 mg/kg/day) during the course. Bronchoalveolar lavage (BAL) was performed in 3 cases with pulmonary alveolar proteinosis and one cases with pulmonary atelectasis. Long-term follow-up through the present time revealed 4 deaths and 7 survivors among the cohort.

Conclusion: The c.218T > C (p.Ile73Thr) variant represents a hotspot mutation in the SFTPC gene, clinically manifesting as ILDs. The therapeutic efficacy of Hch in managing ILDs has been increasingly recognized in clinical practice. BAL is assuming a growing role in both the diagnosis and treatment of SFTPC-related pediatric ILD. Given the heterogeneity of mutation sites, the pathogenic mechanisms underlying lung injury may vary among patients, underscoring the need for personalized diagnostic and therapeutic strategies tailored to specific genetic profiles.