Genetic Dysfunctions of the Surfactant System in Children: Results of a Multicenter Study
Authors:   Peoples’ Friendship University of Russia, Morozovskaya Children Clinical Hospital of Moscow Department of Public Health, Ovsyannikov D.Yu. ,   Moscow, Russian Federation, Zhestkova M.A. ,   Peoples’ Friendship University of Russia; Moscow, Russian Federation, Strelnikova V.A. ,   Peoples’ Friendship University of Russia; Moscow, Russian Federation, Averin A.P. ,   Children's City Clinical Hospital No. 8; Chelyabinsk, Russian Federation, Atipaeva M.A. ,   Children's City Clinical Hospital No. 8; Chelyabinsk, Russian Federation, Brunova O.Yu. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Buyanova G.V. ,   Chelyabinsk Regional Children's Clinical Hospital; Chelyabinsk, Russian Federation, Weinstein N.P. ,   N.I. Pirogov Russian National Research Medical University, G.N. Speransky City Children's Hospital No. 9; Moscow, Russian Federation, Volchikhin M.V. ,   Chelyabinsk Regional Pathological Bureau; Chelyabinsk, Russian Federation, Girutskaya I.V. ,   G.N. Speransky City Children's Hospital No. 9; Moscow, Russian Federation, Davydova I.V. ,   National Medical Research Center for Children's Health; Moscow, Russian Federation, Zhakota D.A. ,   N.I. Pirogov Russian National Research Medical University, N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health; Moscow, Russian Federation, Kovalenko I.V. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Korol K.D. ,   Children's City Clinical Hospital No. 8; Chelyabinsk, Russian Federation, Kuznetsova A.A. ,   Saint Petersburg State Pediatric Medical University; Saint Petersburg, Russian Federation, Krushelnitsky A.A. ,   Moscow Regional Perinatal Center; Balashikha, Russian Federation, Malakhov A.B. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health, I.M. Sechenov First Moscow State Medical University; Moscow, Russian Federation, Malyutina L.V. ,   Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky, Schelkovsky Perinatal Center; Moscow, Russian Federation, Mamaeva E.A. ,   V.A. Almazov National Medical Research Centre; Saint Petersburg, Russian Federation, Marshalkina T.V. ,   Scientific Center of Pediatrics and Pediatric Surgery; Almaty, Kazakhstan, Migali A.I. ,   N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health; Moscow, Russian Federation, Orlov A.V. ,   St. Olga Children’s Hospital (St. Petersburg), North-Western State Medical University named after I.I. Mechnikov; Saint Petersburg, Russian Federation, Pastarnak A.Yu. ,   Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky, Schelkovsky Perinatal Center; Moscow, Russian Federation, Petrova S.I. ,   Saint Petersburg State Pediatric Medical University; Saint Petersburg, Russian Federation, Petryaikina Е.Е. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health, N.I. Pirogov Russian National Research Medical University; Moscow, Russian Federation, Petryaikina Е.S. ,   Peoples’ Friendship University of Russia, Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Prokopiev G.G. ,   N.I. Pirogov Russian National Research Medical University, V.F. Voyno-Yasenetsky Scientific and Practical Center of Spicialized Medical Care for Children; Moscow, Russian Federation, Pushkov A.A. ,   National Medical Research Center for Children's Health; Moscow, Russian Federation, Savostyanov K.V. ,   National Medical Research Center for Children's Health; Moscow, Russian Federation, Sigova Yu.A. Sigova ,   N.I. Pirogov Russian National Research Medical University; Moscow, Russian Federation, Skobeev D.A. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Sudakova O.V. ,   Vologda Regional Children's Hospital No. 2; Cherepovets, Russian Federation, Talalaev A.G. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health, N.I. Pirogov Russian National Research Medical University; Moscow, Russian Federation, Topilin O.G. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Traube M.A. ,   N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health; Moscow, Russian Federation, Fisenko A.P. ,   National Medical Research Center for Children's Health; Moscow, Russian Federation, Kholopova A.Yu. ,   Chelyabinsk Regional Pathological Bureau, South-Ural State Medical University; Chelyabinsk, Russian Federation, Tsverava A.G. ,   Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; Moscow, Russian Federation, Tsokova N.B. ,   G.N. Speransky City Children's Hospital No. 9; Moscow, Russian Federation, Cherkasova S.V. ,   N.I. Pirogov Russian National Research Medical University, N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health; Moscow, Russian Federation
Published: June 2023

Aim: Genetic, clinical, laboratory-instrumental and morphological characteristics of genetic dysfunctions of the surfactant system in children, therapy and outcomes of the disease. Design: Multicentre, ambispective, open-label, descriptive pilot longitudinal study. Materials and methods. We observed 17 children from 16 families with identified mutations in the SFTPC, ABCA3, NKX2-1 genes. Methods used: genealogical, Sanger sequencing, clinical exome sequencing, computed tomography and histological examination of the lungs. Results. The study included 8 children with congenital deficiency of surfactant protein C, 8 children with brain-lung-thyroid syndrome and 1 patient with congenital deficiency of protein ABSA3. Based on the results of a genetic examination of patients, nucleotide variants c.218T>C were identified in 2 out of 8 patients with a mutation in the SFTPC gene, which is the most common according to the literature. In 5 children, the mutations were hereditary. Congenital deficiency of surfactant protein C, ABCA3 protein and brain-lung-thyroid syndrome were characterized by clinical, computed tomography, and morphological signs of interstitial lung disease. Despite complex respiratory, anti-inflammatory therapy, the frequency of deaths in congenital deficiency of surfactant protein C was 37.5%. Conclusion. Children with severe respiratory distress syndrome of newborns, interstitial lung disease with the development of severe chronic respiratory failure, burdened with a family history should undergo genetic testing to detect mutations in the genes SFTPB, SFTPC, ABCA3. The patient's combination of respiratory symptoms with congenital hypothyroidism and neurological pathology is the basis for genetic examination for NKX2-1 gene mutations to exclude the brain-lung-thyroid syndrome. Keywords: genetic dysfunctions of the surfactant system, congenital deficiency of surfactant protein C, congenital deficiency of ABCA3 protein, brain-lung-thyroid syndrome, NKX2-1 gene, children.