Heterogeneity of phenotypic manifestations of cystic fibrosis in children and predictors of the disease severity





cystic fibrosis, CFTR gene, “mild” genotype, “severe” genotype, predictors, children


The aim of the study was to investigate the heterogeneity of phenotypic manifestations of cystic fibrosis (CF) in children depending on the CFTR gene mutation and to determine predictors of the disease severity for the personalization of treatment and prevention of complications.

Materials and methods. Fifty-nine children with CF, aged 1 to 18 years (mean age was 12.0 (8.5; 15.0) years), were examined. All patients underwent general clinical, genetic, laboratory and microbiological examination. Instrumental methods of examination included spirometry, chest X-ray and computed tomography, ultrasound densitometry. According to the functional effects of CFTR mutations, the patients were divided into two groups. The group with “severe” genotypes (n = 40) included patients with two class I and/or II mutations, and the group with “mild” genotypes (n = 10) included patients with at least one class IV or V mutation. Mutations were not identified in 9 patients.

Results. Analysis of the spectrum of genetic variants in the CFTR gene showed that 10 patients (20.0 %) were identified with the “mild” genotype, and 40 patients (80.0 %) with the “severe” genotype. The most common mutation was F508del predominantly in the compound heterozygous state (42.4 %). It was found that patients with the “mild” genotype were characterized by a more favorable course of the disease than patients with the “severe” genotype. No statistically significant phenotypic features of the CF course in children depending on the F508del mutation status (F508del/F508del or F508del/nonF508del) were found, except for earlier formation of pulmonary hypertension in patients with the homozygous condition (47.1% vs 16.0 %, P < 0.05).

Conclusions. Examination of the relationship between CFTR genotype and phenotype has revealed associations between CFTR mutations and lesion severity of both the digestive and bronchopulmonary systems. Identification of disease severity predictors can provide a more accurate prediction of the disease course, that will determine the patient management and prevent the development of complications.

Author Biographies

K. V. Skriabina, Dnipro State Medical University, Ukraine

MD, Assistant of the Department of Propaedeutics of Children’s Diseases

S. I. Ilchenko, Dnipro State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Propaedeutics of Children’s Diseases

A. O. Fialkovska, Dnipro State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Propaedeutics of Children’s Diseases


Berezenko, V. S., Reznikov, Yu. P., & Krat, V. V. (2017). Mukovistsydoz u ditei. Svoiechasna diahnostyka yak vazhlyvyi predyktor efektyvnosti likuvannia (klinichnyi vypadok). [Cystic fibrosis in children. Early diagnosis as important predictor of treatment efficiency (clinical case)]. Perinatology and pediatric. Ukraine, (3), 74-80. [in Ukrainian]. https://doi.org/10.15574/PP.2017.71.74

Senatorova, G. S., Tel'nova, L. G., Chernenko, L. N., Polyakov, V. V., Bashkirova, N. V., & Strelkova, M. I. (2019). Rol henetychnykh ta medyko-sotsialnykh faktoriv u perebihu mukovistsydozu. Klinichne sposterezhennia [The Role of Genetic and Medical-social Factors in the Course of Cystic Fibrosis. Clinical Cases]. Ukrainian Journal of Medicine, Biology and Sport, 4(2), 173-180. [in Ukrainian].

Gurwitz, D., Corey, M., Francis, P. W., Crozier, D., & Levison, H. (1979). Perspectives in cystic fibrosis. Pediatric clinics of North America, 26(3), 603-615. https://doi.org/10.1016/s0031-3955(16)33752-x

Cystic Fibrosis Mutation Database (СFTR1). http://genet.sickkids.on.ca

The Clinical and Functional Translation of CFTR (CFTR2). https://www.cftr2.org

Dechecchi, M. C., Tamanini, A., & Cabrini, G. (2018). Molecular basis of cystic fibrosis: from bench to bedside. Annals of translational medicine, 6(17), 334. https://doi.org/10.21037/atm.2018.06.48

Castellani, C., Cuppens, H., Macek, M., Jr, Cassiman, J. J., Kerem, E., Durie, P., Tullis, E., Assael, B. M., Bombieri, C., Brown, A., Casals, T., Claustres, M., Cutting, G. R., Dequeker, E., Dodge, J., Doull, I., Farrell, P., Ferec, C., Girodon, E., Johannesson, M., … Elborn, J. S. (2008). Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. Journal of cystic, 7(3), 179-196. https://doi.org/10.1016/j.jcf.2008.03.009

Rafeey, M., Jabarpoor-Bonyadi, M., & Vahedi, L. (2020). Genotype-Phenotype Correlation for Cystic Fibrosis According to Registry Center of Cystic Fibrosis. Crescent Journal of Medical and Biological Sciences, 7(1), 124-129.

Singh, M., Rebordosa, C., Bernholz, J., & Sharma, N. (2015). Epidemiology and genetics of cystic fibrosis in Asia: In preparation for the next-generation treatments. Respirology (Carlton, Vic.), 20(8), 1172-1181. https://doi.org/10.1111/resp.12656

Alfonso-Sánchez, M. A., Pérez-Miranda, A. M., García-Obregón, S., & Peña, J. A. (2010). An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European populations. Medical hypotheses, 74(6), 989-992. https://doi.org/10.1016/j.mehy.2009.12.018

Salvatore, F., Scudiero, O., & Castaldo, G. (2002). Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes. American journal of medical genetics, 111(1), 88-95. https://doi.org/10.1002/ajmg.10461

Cystic Fibrosis Foundation. (2020). Cystic Fibrosis Foundation Patient Registry. Annual Data Report 2020. https://www.cff.org

Santos, C. de S., & Steemburgo, T. (2015). Nutrional status and dietary factors in cystic fibrosis patients with delta F508 mutation. Revista de Nutricao, 28(4), 359-369. https://doi.org/10.1590/1415-52732015000400003

Farra, C., Menassa, R., Awwad, J., Morel, Y., Salameh, P., Yazbeck, N., Majdalani, M., Wakim, R., Yunis, K., Mroueh, S., & Cabet, F. (2010). Mutational spectrum of cystic fibrosis in the Lebanese population. Journal of cystic fibrosis, 9(6), 406-410. https://doi.org/10.1016/j.jcf.2010.08.001

Gökdemir, Y., Erdem, E., Akpinar, I. N., Ersu, R., Karadaǧ, B., & Karakoç, F. (2012). Other risk factors associated with mortality in moderate and severe cystic fibrosis patients. Turk Pediatri Arsivi, 47(4), 267-271. https://doi.org/10.4274/tpa.901

Ilchenko, S. I., Fialkovska, A. O., Cherhinets, V. I., & Skriabina, K. V. (2021). Porivniannia efektyvnosti ta perenosymosti inhaliatsiinykh hipertonichnykh rozchyniv khlorydu natriiu v pediatrychnii praktytsi [Comparison of the efficacy and tolerability of inhaled hypertonic salines of sodium chloride in pediatric practice]. Medychni perspektyvy, 26(1), 136-142. [in Ukrainian]. https://doi.org/10.26641/2307-0404.2021.1.227953

Janahi, I. A., Rehman, A., & Al-Naimi, A. R. (2017). Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Annals of thoracic medicine, 12(2), 74-82. https://doi.org/10.4103/atm.ATM_231_16

Aris, R. M., Merkel, P. A., Bachrach, L. K., Borowitz, D. S., Boyle, M. P., Elkin, S. L., Guise, T. A., Hardin, D. S., Haworth, C. S., Holick, M. F., Joseph, P. M., O'Brien, K., Tullis, E., Watts, N. B., & White, T. B. (2005). Guide to bone health and disease in cystic fibrosis. The Journal of clinical endocrinology and metabolism, 90(3), 1888-1896. https://doi.org/10.1210/jc.2004-1629

Chesdachai, S., & Tangpricha, V. (2016). Treatment of vitamin D deficiency in cystic fibrosis. The Journal of steroid biochemistry and molecular biology, 164, 36-39. https://doi.org/10.1016/j.jsbmb.2015.09.013

Abu-Fraiha, Y., Elyashar-Earon, H., Shoseyov, D., Cohen-Cymberknoh, M., Armoni, S., Kerem, E., & Wilschanski, M. (2015). WS04.5 Vitamin D influence on respiratory exacerbations and hospitalizations in cystic fibrosis patients. Journal of Cystic Fibrosis, 14, S8. https://doi.org/10.1016/s1569-1993(15)30025-4



How to Cite

Skriabina KV, Ilchenko SI, Fialkovska AO. Heterogeneity of phenotypic manifestations of cystic fibrosis in children and predictors of the disease severity. Zaporozhye medical journal [Internet]. 2022Dec.20 [cited 2024Feb.24];24(6):674-80. Available from: http://zmj.zsmu.edu.ua/article/view/258359



Original research