Genetic Dysfunctions of the Surfactant System in Children: Results of a Multicenter Study

D. Yu. Ovsyannikov; M. A. Zhestkova; V. A. Strelnikova; A. P. Averin; M. А. Atipaeva; O. Yu. Brunova; G. V. Buyanova; N. P. Weinstein; M. V. Volchikhin; I. V. Girutskaya; I. V. Davydova; D. A. Zhakota; I. V. Kovalenko; K. D. Korol; A. A. Kuznetsova; A. A. Krushelnitsky; A. B. Malakhov; L. V. Malyutina; E. A. Mamaeva; T. V. Marshalkina; A. I. Migali; A. V. Orlov; A. Yu. Pastarnak; S. I. Petrova; Е. Е. Petryaikina; Е. S. Petryaikina; G. G. Prokopiev; A. A. Pushkov; K. V. Savostyanov; Yu. A. Sigova; D. A. Skobeev; O. V. Sudakova; A. G. Talalaev; O. G. Topilin; M. A. Traube; A. P. Fisenko; A. Yu. Kholopova; A. G. Tsverava; N. B. Tsokova; S. V. Cherkasova

doi:10.31550/1727-2378-2023-22-3-22-31

Genetic Dysfunctions of the Surfactant System in Children: Results of a Multicenter Study

D. Yu. Ovsyannikov, M. A. Zhestkova, V. A. Strelnikova, A. P. Averin, M. А. Atipaeva, O. Yu. Brunova, G. V. Buyanova, N. P. Weinstein, M. V. Volchikhin, I. V. Girutskaya, I. V. Davydova, D. A. Zhakota, I. V. Kovalenko, K. D. Korol, A. A. Kuznetsova, A. A. Krushelnitsky, A. B. Malakhov, L. V. Malyutina, E. A. Mamaeva, T. V. Marshalkina, A. I. Migali, A. V. Orlov, A. Yu. Pastarnak, S. I. Petrova, Е. Е. Petryaikina, Е. S. Petryaikina, G. G. Prokopiev, A. A. Pushkov, K. V. Savostyanov, Yu. A. Sigova, D. A. Skobeev, O. V. Sudakova, A. G. Talalaev, O. G. Topilin, M. A. Traube, A. P. Fisenko, A. Yu. Kholopova, A. G. Tsverava, N. B. Tsokova, S. V. Cherkasova

https://doi.org/10.31550/1727-2378-2023-22-3-22-31

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Abstract

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

About the Authors

D. Yu. Ovsyannikov

Peoples’ Friendship University of Russia; Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

M. A. Zhestkova

Peoples’ Friendship University of Russia
Russian Federation

V. A. Strelnikova

Peoples’ Friendship University of Russia
Russian Federation

A. P. Averin

Children's City Clinical Hospital No. 8
Russian Federation

Chelyabinsk

M. А. Atipaeva

Children's City Clinical Hospital No. 8
Russian Federation

Chelyabinsk

O. Yu. Brunova

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

G. V. Buyanova

Chelyabinsk Regional Children's Clinical Hospital
Russian Federation

N. P. Weinstein

N.I. Pirogov Russian National Research Medical University, G.N. Speransky City Children's Hospital No. 9
Russian Federation

M. V. Volchikhin

Chelyabinsk Regional Pathological Bureau
Russian Federation

I. V. Girutskaya

G.N. Speransky City Children's Hospital No. 9
Russian Federation

I. V. Davydova

National Medical Research Center for Children's Health
Russian Federation

D. A. Zhakota

N.I. Pirogov Russian National Research Medical University; N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health
Russian Federation

I. V. Kovalenko

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

K. D. Korol

Children's City Clinical Hospital No. 8
Russian Federation

Chelyabinsk

A. A. Kuznetsova

Petersburg State Pediatric Medical University
Russian Federation

A. A. Krushelnitsky

Moscow Regional Perinatal Center
Russian Federation

Balashikha

A. B. Malakhov

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; I.M. Sechenov First Moscow State Medical University
Russian Federation

L. V. Malyutina

Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky; Schelkovsky Perinatal Center
Russian Federation

E. A. Mamaeva

V.A. Almazov National Medical Research Centre
Russian Federation

T. V. Marshalkina

Scientific Center of Pediatrics and Pediatric Surgery
Russian Federation

Almaty

A. I. Migali

N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health
Russian Federation

A. V. Orlov

St. Olga Children’s Hospital (St. Petersburg), North-Western State Medical University named after I.I. Mechnikov
Russian Federation

A. Yu. Pastarnak

Moscow Regional Research and Clinical Institute named after M.F. Vladimirsky, Schelkovsky Perinatal Center
Russian Federation

S. I. Petrova

Saint Petersburg State Pediatric Medical University
Russian Federation

Е. Е. Petryaikina

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; N.I. Pirogov Russian National Research Medical University
Russian Federation

Е. S. Petryaikina

Peoples’ Friendship University of Russia, Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

G. G. Prokopiev

N.I. Pirogov Russian National Research Medical University; V.F. Voyno-Yasenetsky Scientific and Practical Center of Spicialized Medical Care for Children
Russian Federation

A. A. Pushkov

National Medical Research Center for Children's Health
Russian Federation

K. V. Savostyanov

National Medical Research Center for Children's Health
Russian Federation

Yu. A. Sigova

N.I. Pirogov Russian National Research Medical University
Russian Federation

D. A. Skobeev

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

O. V. Sudakova

Vologda Regional Children's Hospital No. 2
Russian Federation

Cherepovets

A. G. Talalaev

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health; N.I. Pirogov Russian National Research Medical University
Russian Federation

O. G. Topilin

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

M. A. Traube

N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health
Russian Federation

A. P. Fisenko

National Medical Research Center for Children's Health
Russian Federation

A. Yu. Kholopova

Chelyabinsk Regional Pathological Bureau; South-Ural State Medical University
Russian Federation

A. G. Tsverava

Morozovskaya Children Clinical Hospital of Moscow Department of Public Health
Russian Federation

N. B. Tsokova

G.N. Speransky City Children's Hospital No. 9
Russian Federation

S. V. Cherkasova

N.I. Pirogov Russian National Research Medical University; N.F. Filatov Chldren’s City Hospital of the Department Moscow Department of Public Health
Russian Federation

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For citations:

Ovsyannikov D.Yu., Zhestkova M.A., Strelnikova V.A., Averin A.P., Atipaeva M.А., Brunova O.Yu., Buyanova G.V., Weinstein N.P., Volchikhin M.V., Girutskaya I.V., Davydova I.V., Zhakota D.A., Kovalenko I.V., Korol K.D., Kuznetsova A.A., Krushelnitsky A.A., Malakhov A.B., Malyutina L.V., Mamaeva E.A., Marshalkina T.V., Migali A.I., Orlov A.V., Pastarnak A.Yu., Petrova S.I., Petryaikina Е.Е., Petryaikina Е.S., Prokopiev G.G., Pushkov A.A., Savostyanov K.V., Sigova Yu.A., Skobeev D.A., Sudakova O.V., Talalaev A.G., Topilin O.G., Traube M.A., Fisenko A.P., Kholopova A.Yu., Tsverava A.G., Tsokova N.B., Cherkasova S.V. Genetic Dysfunctions of the Surfactant System in Children: Results of a Multicenter Study. PEDIATRICS. 2023;22(3):22-31. (In Russ.) https://doi.org/10.31550/1727-2378-2023-22-3-22-31

This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1727-2378 (Print)
ISSN 2713-2994 (Online)

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Title

Genetic Dysfunctions of the Surfactant System in Children: Results of a Multicenter Study

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