russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2014-5-55-60russjcardiol-70Research ArticleМИОКАРДИТЫ, КЛАПАННЫЕ И НЕКОРОНАРОГЕННЫЕ ЗАБОЛЕВАНИЯMYOCARDITISES, VALVULAR AND NONCORONAROGENIC DISEASESНЕОНАТАЛЬНАЯ ФОРМА СИНДРОМА МАРФАНА — КЛИНИЧЕСКОЕ ОПИСАНИЕ И КОМПЛЕКСНЫЙ ПОДХОД К ДИАГНОСТИКЕ И ЛЕЧЕНИЮNEONATAL MARFAN SYNDROME: CLINICAL DESCRIPTION AND COMPLEX APPROACH TO DIAGNOSTICS AND TREATMENTРумянцеваВ. А.RumyantsevaV. A.

к. м.н., врач-генетик лаборатории медицинской генетики

vicrumyan@gmail.comРогожинаЮ. А.RogozhinaYu. A.

лаборант-исследователь лаборатории медицинской генетики

КотлуковаН. П.KotlukovaN. P.

д. м.н., профессор

ЗаклязьминскаяE. В.ZaklyazminskayaE. V.

д. м.н., профессор, руководитель лаборатории медицинской генетики

ФГБУ РНЦХ имени академика Б. В. Петровского, МоскваРоссияFSBI Petrovsky Russian Scientific Centre for Surgery, MoscowRussian FederationПеринатальный кардиологический центр, Москва, РоссияРоссияPerinatal Cardiovascular Centre, Moscow, RussiaRussian Federation201428052014055560Copyright © Румянцева В.А., Рогожина Ю.А., Котлукова Н.П., Заклязьминская E.В., 20142014Румянцева В.А., Рогожина Ю.А., Котлукова Н.П., Заклязьминская E.В.Rumyantseva V.A., Rogozhina Y.A., Kotlukova N.P., Zaklyazminskaya E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/70Материал и методы

Материал и методы. Медико-генетическое консультирование и данные инструментальных методов (ЭХО-КГ, ДС сосудов, ЭКГ, рентгенография грудной клетки) дали возможность предположить диагноз неонатальной формы синдрома Марфана. Прямая ДНК-диагностика СМ для этих больных, включающая прямое секвенирование по Сенгеру кодирующих участков и прилегающих интронных областей экзонов 24–32 гена FBN1, полностью подтвердила предполагаемый диагноз.

Результаты

Результаты. Впервые в России в двух неродственных семьях с детьми первого года жизни, с множественными аномалиями развития внешности был поставлен диагноз синдрома Марфана на первом году жизни и подтвержден молекулярно-генетическими методами.

Заключение

Заключение. Результаты исследования должны быть внедрены в практическую работу специализированных педиатрических, кардиологических и кардиохирургических центров и отделений для оценки риска внезапной смерти, выбора тактики лечения, назначении генноспецифической терапии.

 

 

 

 

 

 

Aim

Aim. Molecular-genetic tests for neonatal type of Mrfan syndrome make possible to clarify a dignosis in children with multiple phenotype anomalies and to choose correct treatment strategy.

Material and methods

Material and methods. Medical-genetic testing and instrumental diagnostics (echo, Doppler, ECG, chest X-rays) made possible to guess the diagnosis of neonatal Marfan syndrome (MS). Direct DNA-diagnostics of MS for these patients including direct Senger-sequencing of the coding plots and neighbouring introne areas of exones 24-32 gene FBN1 completely proved the diagnosis. Results. First time in Russia in two non-relative families with newborns having multiple phenotype anomalies the diagnosis of MS was set at the first year of life and confirmed by molecular-genetic methods.

Conclusion

Conclusion. The results of the study must be introduced into practice at specialized pediatric, cardiological and cardiosurgical centres and departments to estimate the risk of sudden death, choose treatment strategy, prescribe gene-specific therapy.

синдром МарфанафибриллинДНК-диагностикагенетическое консультирование в кардиологииMarfan syndromefibrilinDNA-diagnosticsgenetic consulting in cardiologyReferencesFaivre L, Paulet AM, Beroud GC, et al. Clinical and molecular study of 320 children with Marfan syndrome and related type 1 fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations. Pediatrics 2009; 123: 391-8.Faivre L, Paulet AM, Beroud GC, et al. Clinical and molecular study of 320 children with Marfan syndrome and related type 1 fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations. Pediatrics 2009; 123: 391-8.Ramaswamy P, Lytrivi ID., Nguyen K, et al. Neonatal Marfan Syndrome. In Utero Presentation with Aortic and Pulmonary Artery Dilatation and successful Repair of an Acute Flail Mitral Valve Leaflet in Infancy, Pediatr Cardiol 2006, 27: 763-5.Ramaswamy P, Lytrivi ID., Nguyen K, et al. Neonatal Marfan Syndrome. In Utero Presentation with Aortic and Pulmonary Artery Dilatation and successful Repair of an Acute Flail Mitral Valve Leaflet in Infancy, Pediatr Cardiol 2006, 27: 763-5.Rozendaal L, Blom NA, Hilhorst-Hofstee X et al. Dilatation of the Great Arteries in an Infant with Marfan Syndrome and Ventricular Septal Defect. Case Reports in Medicine е 2011, 172109.Rozendaal L, Blom NA, Hilhorst-Hofstee X et al. Dilatation of the Great Arteries in an Infant with Marfan Syndrome and Ventricular Septal Defect. Case Reports in Medicine е 2011, 172109.Ghandi X Zanjani KS, Mazhari-Mousavi S. Neonatal Marfan Syndrome: Report of Two Cases.Iranian Journal of Pediatrics 2013, 23: 113-7.Ghandi X Zanjani KS, Mazhari-Mousavi S. Neonatal Marfan Syndrome: Report of Two Cases.Iranian Journal of Pediatrics 2013, 23: 113-7.Brito-Filho SL, Oporto V, Campos O, et al. A case of neonatal Marfan syndrome with good late follow-up: is it possible to avoid an early unfavourable outcome?, Brazil Cardiology in the Xoung 2013, 23, 301-3.Brito-Filho SL, Oporto V, Campos O, et al. A case of neonatal Marfan syndrome with good late follow-up: is it possible to avoid an early unfavourable outcome?, Brazil Cardiology in the Xoung 2013, 23, 301-3.Kirschner R., Hubmacher D, Reinhardt DP, et al. Classical and neonatal Marfan syndrome mutations in fibrillin-1 cause differential protease susceptibilities and protein function. J. of Biological Chemistry 2011, 286 (37): 32810-23.Kirschner R., Hubmacher D, Reinhardt DP, et al. Classical and neonatal Marfan syndrome mutations in fibrillin-1 cause differential protease susceptibilities and protein function. J. of Biological Chemistry 2011, 286 (37): 32810-23.Tiecke F, Katzke S, Booms P, et al. Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40, European Journal of Human Genetics 2001, 9, 13-21.Tiecke F, Katzke S, Booms P, et al. Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40, European Journal of Human Genetics 2001, 9, 13-21.Sukhorukov VS, Klyuchnikov SO. Effective correction of metabolic disorders in children: energotropic therapy. Russian journal of Perinatology and Pediatrics 2006, 51 (6): 79-87. Russian (Сухоруков В. С., Ключников С. О. Рациональная коррекция метаболических нарушений у детей: энерготропная терапия. Российский вестник перинатологии и педиатрии 2006, 51 (6): 79-87).Sukhorukov VS, Klyuchnikov SO. Effective correction of metabolic disorders in children: energotropic therapy. Russian journal of Perinatology and Pediatrics 2006, 51 (6): 79-87. Russian (Сухоруков В. С., Ключников С. О. Рациональная коррекция метаболических нарушений у детей: энерготропная терапия. Российский вестник перинатологии и педиатрии 2006, 51 (6): 79-87).Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome.Journal of Medical Genetics 2010, 47: 476-85.Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome.Journal of Medical Genetics 2010, 47: 476-85.Elshershari H, Harris C..Paternal fibrillin-1 mutation transmitted to an affected son with neonatal marfan syndrome: the importance of early recognition. Cardiology in the Xoung 2013, 1-4.Elshershari H, Harris C..Paternal fibrillin-1 mutation transmitted to an affected son with neonatal marfan syndrome: the importance of early recognition. Cardiology in the Xoung 2013, 1-4.Tekin M, Cengiz F, Ayberkin E. Familial Neonatal Marfan Syndrome Due to Parental Mosaicism of a Missense Mutation in the FBN1 Gene American Journal of Medical Genetics 2007, 143A: 875-80.Tekin M, Cengiz F, Ayberkin E. Familial Neonatal Marfan Syndrome Due to Parental Mosaicism of a Missense Mutation in the FBN1 Gene American Journal of Medical Genetics 2007, 143A: 875-80.Sipek A, Grodecka L, Baxova A, et al. Novel FBN1 gene mutation and maternal germinal mosaicism as the cause of neonatal form of Marfan syndrome. Am J Med Genet 2014, Part A 9999: 1-6.Sipek A, Grodecka L, Baxova A, et al. Novel FBN1 gene mutation and maternal germinal mosaicism as the cause of neonatal form of Marfan syndrome. Am J Med Genet 2014, Part A 9999: 1-6.Olivieri J, Smaldone S, Ramirez F. Fibrillin assemblies: extracellular determinants of tissue formation and fibrosis. Fibrogenesis & Tissue Repair 2010, 3-24.Olivieri J, Smaldone S, Ramirez F. Fibrillin assemblies: extracellular determinants of tissue formation and fibrosis. Fibrogenesis & Tissue Repair 2010, 3-24.Burchett ME, Ling IF, Estus S. FBN1 isoform expression varies in a tissue and development-specific fashion. Biochemical and Biophysical Research Communications 2011: 323-8.Burchett ME, Ling IF, Estus S. FBN1 isoform expression varies in a tissue and development-specific fashion. Biochemical and Biophysical Research Communications 2011: 323-8.Summers KM, Bokil NJ, Baisden JM, et al. Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1. Hume Genomics2009, 94: 233-40.Summers KM, Bokil NJ, Baisden JM, et al. Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1. Hume Genomics2009, 94: 233-40.Mullen MJ, Flather MD, Jin XX A prospective, randomized, placebo-controlled, double- blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol, Trials 2013, 14: 408.Mullen MJ, Flather MD, Jin XX A prospective, randomized, placebo-controlled, double- blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol, Trials 2013, 14: 408.Lacro RV, Guey LT, Dietz HC. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. Am Heart J. 2013; 165 (5): 828-35.Lacro RV, Guey LT, Dietz HC. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. Am Heart J. 2013; 165 (5): 828-35.Tinkle BT, Saal HM and the committee on genetics. Health Supervision for Children With Marfan Syndrome, Pediatrics 2013, 132; 1059-72.Tinkle BT, Saal HM and the committee on genetics. Health Supervision for Children With Marfan Syndrome, Pediatrics 2013, 132; 1059-72.

The authors declare that there are no conflicts of interest present.