russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2018-10-151-158russjcardiol-2798Research ArticleОБЗОРЫREVIEWСиндром Карвахаль: краткий обзор и клинический случай кардиомиопатии, ассоциированной с компаунд гетерозиготными мутациями гена десмоплакинаCarvajal syndrome: a brief overview and clinical case of cardiomyopathy, associated with compound heterozygous mutations of the desmoplakin genehttps://orcid.org/0000-0002-2127-8525ВайханскаяТ. Г.VaikhanskayaT. G.

Вайханская Татьяна Геннадьевна - кандидат медицинских наук, ведущий научный сотрудник лаборатории медицинских информационных технологий.

Минск.

SPIN-код:2783-2641 

Minsk.

tat_vaikh@mail.ruhttps://orcid.org/0000-0001-6359-4967СивицкаяЛ. Н.SivitskayaL. N.

Сивицкая Лариса Николаевна - кандидат биологических наук, старший научный сотрудник лаборатории нехромосомной наследственности.

Минск.

Minsk.

cytoplasmic@mail.ruhttps://orcid.org/0000-0001-5727-3219КурушкоТ. В.KurushkoT. V.

Курушко Татьяна Валентиновна — врач отделения функциональной диагностики.

Минск.

Minsk.

tat_kuko@mail.ruhttps://orcid.org/0000-0002-0712-6939ЕрмаковичД. П.ErmakovichD. P.

Ермакович Донат Петрович — младший научный сотрудник лаборатории нехромосомной наследственности.

Минск.

Minsk.

cytoplasmic@mail.ruhttps://orcid.org/0000-0003-0778-6512ЗасимЕ. В.ZasimE. V.

Засим Елена Владимировна - заведующая консультативно-поликлиническим отделом.

Минск.

Minsk.

info@dhc.byhttps://orcid.org/0000-0002-3270-3080ДаниленкоН. Г.DanilenkoN. G.

Даниленко Нина Генусовна — кандидат биологических наук, ведущий научный сотрудник лаборатории нехромосомной наследственности.

Минск.

Minsk.

cytoplasmic@mail.ruРеспубликанский научно-практический центр «Кардиология»БеларусьRepublican Scientific and Practical Center «Cardiology»BelarusИнститут генетики и цитологии НАН БеларусиБеларусьThe Institute of Genetics and Cytology of the National Academy of Sciences of BelarusBelarusРеспубликанский научно-практический центр детской хирургииБеларусьThe Republican Scientific and Practical Center for Pediatric SurgeryBelarus201824112018010151158Copyright © Вайханская Т.Г., Сивицкая Л.Н., Курушко Т.В., Ермакович Д.П., Засим Е.В., Даниленко Н.Г., 20182018Вайханская Т.Г., Сивицкая Л.Н., Курушко Т.В., Ермакович Д.П., Засим Е.В., Даниленко Н.Г.Vaikhanskaya T.G., Sivitskaya L.N., Kurushko T.V., Ermakovich D.P., Zasim E.V., Danilenko N.G.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/2798

Мутации в генах, кодирующих десмосомальные белки, являются причиной широкого спектра заболеваний с аномалиями кожи, волос и сердца; в 45-50% случаев эти мутации детерминируют развитие аритмогенной правожелудочковой кардиомиопатии. Сегодня известно более 120 аутосомно-доминантных и аутосомно-рецессивных мутаций гена десмоплакина (DSP), вызывающих кожно-кардиальную патологию. В статье представлен впервые выявленный в Восточной Европе (Беларусь) редкий клинический случай синдрома Карвахаль (OMIM 605676), ассоциированного с компаунд гетерозиготными мутациями, с классической триадой признаков (фенотип дилатационной кардиомиопатии, кератодермия и шерстисто-курчавые волосы). Краткий литературный обзор проблемы и вопросы дифференциальной диагностики представлены в статье в виде сравнительного анализа синдрома Карвахаль с фенотипически сходной патологией — синдромом Наксос, обусловленным мутациями в гене, кодирующем другой десмосомальный белок — плакоглобин (синдром Наксос, OMIM 601214), и приводящими к развитию аритмогенной правожелудочковой кардиомиопатии.

Mutations in the genes encoding desmosomal proteins cause a wide range of diseases associated with abnormalities of the skin, hair and heart. In 45-50% these mutations determine the development of arrhythmogenic right ventricular cardiomyopathy. Today, more than 120 autosomal dominant and autosomal recessive mutations of the desmoplakin (DSP) gene are known, causing skin and cardiac disorders. The article presents a rare clinical case of Carvajal syndrome (OMIM 605676), associated with compound heterozygous mutations, with the classic triad of symptoms (the phenotype of dilated cardiomyopathy, keratoderma, and woolly hair), which was first identified in Eastern Europe (Belarus). A brief literature review of the problems and issues of differential diagnosis are presented in the article in the form of a comparative analysis of Carvajal syndrome with phenotypically similar pathology - Naxos syndrome, caused by mutations in the gene encoding another desmosomal protein - Placoglobin (Naxos syndrome, OMIM 601214), and leading to the development of arrhythmogenic right ventricular cardiomyopathy.

десмоплакиндилатационная кардиомиопатиякератодермиякурчаво-шерстистые волосысиндром Карвахальсиндром Наксосплакоглобинdesmoplakindilated cardiomyopathykeratodermawooly hairCarvajal syndromeNaxos syndromeplacoglobinReferencesCarvajal-Huerta L. Epidermolytic palmoplantar keratoderma with woolly hair and dilated ardiomyopathy J. Am. Acad. Dermatol. 1998;39:418-21. doi:10.1016/S0190-9622(98)70317-2.Carvajal-Huerta L. Epidermolytic palmoplantar keratoderma with woolly hair and dilated ardiomyopathy J. Am. Acad. Dermatol. 1998;39:418-21. doi:10.1016/S0190-9622(98)70317-2.Nehme N, El Malti R, Roux-Buisson N, et al. Evidence for genetic heterogeneity in Carvajal syndrome. Cell Tissue Res. 2012;348(2):261-4. doi:10.1007/s00441-012-1351-6.Nehme N, El Malti R, Roux-Buisson N, et al. Evidence for genetic heterogeneity in Carvajal syndrome. Cell Tissue Res. 2012;348(2):261-4. doi:10.1007/s00441-012-1351-6.Boule S, Fressart V, Laux D, et al. Expanding the phenotype associated with a desmoplakin dominant mutation: Carvajal/Naxos syndrome associated with leukonychia and oligodontia. Int. J. Cardiol. 2012;161:50-2. doi:10.1016/j.ijcard.2012.06.068.Boule S, Fressart V, Laux D, et al. Expanding the phenotype associated with a desmoplakin dominant mutation: Carvajal/Naxos syndrome associated with leukonychia and oligodontia. Int. J. Cardiol. 2012;161:50-2. doi:10.1016/j.ijcard.2012.06.068.Protonotarios N, Tsatsopoulou A. Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Path. 2004; 13(4): 185-94. doi: 10.1016/j.carpath.2004.03.609.Protonotarios N, Tsatsopoulou A. Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Path. 2004; 13(4): 185-94. doi: 10.1016/j.carpath.2004.03.609.Protonotarios N, Tsatsopoulou A, Anastasakis A, et al. Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. J Am Coll Cardiol. 2001;38:1477-84.Protonotarios N, Tsatsopoulou A, Anastasakis A, et al. Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. J Am Coll Cardiol. 2001;38:1477-84.Rickelt S, Pieperhoff S. Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases. Cell Tissue Res. 2012;348:325-33. doi:10.1007/s00441-012-1365-0.Rickelt S, Pieperhoff S. Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases. Cell Tissue Res. 2012;348:325-33. doi:10.1007/s00441-012-1365-0.Baykan A, Olgar S, Argun M, et al. Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature. Anatol J Cardiol. 2015;15(5):404-8. doi:10.5152/akd.2014.5413.Baykan A, Olgar S, Argun M, et al. Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature. Anatol J Cardiol. 2015;15(5):404-8. doi:10.5152/akd.2014.5413.Malcic I, Kniewald H, Jelic A, et al. Carvajal syndrome — rare entity of cardiocutaneous syndrome in a child from the Mediterranean part of Croatia — report on a new mutation of a desmoplakin gene. Cardiol Young. 2015;25(S 1):86. doi:10.1017/S1047951115000529.Malcic I, Kniewald H, Jelic A, et al. Carvajal syndrome — rare entity of cardiocutaneous syndrome in a child from the Mediterranean part of Croatia — report on a new mutation of a desmoplakin gene. Cardiol Young. 2015;25(S 1):86. doi:10.1017/S1047951115000529.Mahoney MG, Sadowski S, Brennan D, et al. Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest Dermatol. 2010;130:968-78. doi :10.1038/jid.2009.357.Mahoney MG, Sadowski S, Brennan D, et al. Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest Dermatol. 2010;130:968-78. doi :10.1038/jid.2009.357.Yesudian PD, Cabral RM, Ladusans E, et al. Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy. Clin Exp Dermatol. 2014;39:506-8. doi:10.1111/ced.12329.Yesudian PD, Cabral RM, Ladusans E, et al. Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy. Clin Exp Dermatol. 2014;39:506-8. doi:10.1111/ced.12329.Sen-Chowdhry S, Syrris P, Prasad SK, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol. 2008;52:2175-87. doi:10.1016/j.jacc.2008.09.019.Sen-Chowdhry S, Syrris P, Prasad SK, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol. 2008;52:2175-87. doi:10.1016/j.jacc.2008.09.019.Smith FJ, Wilson NJ, Moss C, et al. Compound heterozygous mutations in desmoplakin cause skin fragility and woolly hair. Br J Dermatol. 2012;166:894-96. doi:10.1111/jdv.14834.Smith FJ, Wilson NJ, Moss C, et al. Compound heterozygous mutations in desmoplakin cause skin fragility and woolly hair. Br J Dermatol. 2012;166:894-96. doi:10.1111/jdv.14834.Nitoiu D, Etheridge SL, Kelsell DP. Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes. Cell Commun Adhes. 2014;21:129-40. doi:10.3109/15419061.2014.908854.Nitoiu D, Etheridge SL, Kelsell DP. Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes. Cell Commun Adhes. 2014;21:129-40. doi:10.3109/15419061.2014.908854.Patel DM, Green KJ. Desmosomes in the heart: a review of clinical and mechanistic analyses. Cell Commun Adhes. 2014;21:109-28. doi:10.3109/15419061.2014.906533.Patel DM, Green KJ. Desmosomes in the heart: a review of clinical and mechanistic analyses. Cell Commun Adhes. 2014;21:109-28. doi:10.3109/15419061.2014.906533.Molho-Pessach V, Sheffer S, Siam R, et al. Two novel homozygous desmoplakin mutations in Carvajal syndrome. Pediatr. Dermatol. 2015;32:641-46. doi:10.1111/pde.12541.Molho-Pessach V, Sheffer S, Siam R, et al. Two novel homozygous desmoplakin mutations in Carvajal syndrome. Pediatr. Dermatol. 2015;32:641-46. doi:10.1111/pde.12541.Antonov NK, Kingsbery MY, Rohena LO, et al. Early-onset heart failure, alopecia, and cutaneous abnormalities associated with a novel compound heterozygous mutation in desmoplakin. Pediatr. Dermatol. 2015;32:102-8. doi:10.1111/pde.12484.Antonov NK, Kingsbery MY, Rohena LO, et al. Early-onset heart failure, alopecia, and cutaneous abnormalities associated with a novel compound heterozygous mutation in desmoplakin. Pediatr. Dermatol. 2015;32:102-8. doi:10.1111/pde.12484.Madhu KJ, Vijyalakshmi IB, Narsimhan C, et al. Carvajal Syndrome: A Rare Variant of Naxos Disease. Cardiovasc Ther. 2016;1:103.Madhu KJ, Vijyalakshmi IB, Narsimhan C, et al. Carvajal Syndrome: A Rare Variant of Naxos Disease. Cardiovasc Ther. 2016;1:103.Mohammadpour Ahranjani B, Moradi P, Nazari S, et al. A Nine-Year-Old Girl With Left Ventricle Non-Compaction and Skin Lesions (Carvajal Syndrome). Iran J Pediatr. 2015;25(4):e370. doi:10.5812/ijp.370.Mohammadpour Ahranjani B, Moradi P, Nazari S, et al. A Nine-Year-Old Girl With Left Ventricle Non-Compaction and Skin Lesions (Carvajal Syndrome). Iran J Pediatr. 2015;25(4):e370. doi:10.5812/ijp.370.Barber S, Day P, Judge M, et al. Variant Carvajal syndrome with additional dental anomalies. Int J Paediatr Dent. 2012;22(5):390-6. doi:10.1111/j.1365-263X.2012.01230.x.Barber S, Day P, Judge M, et al. Variant Carvajal syndrome with additional dental anomalies. Int J Paediatr Dent. 2012;22(5):390-6. doi:10.1111/j.1365-263X.2012.01230.x.Mahoney MG, Sadowski S, Brennan D, et al. Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest. Dermatol. 2010;130(4):968-78. doi:10.1038/jid.2009.357.Mahoney MG, Sadowski S, Brennan D, et al. Compound heterozygous desmoplakin mutations result in a phenotype with a combination of myocardial, skin, hair, and enamel abnormalities. J Invest. Dermatol. 2010;130(4):968-78. doi:10.1038/jid.2009.357.Norgett EE, Lucke TW, Bowers B, et al. Early death from cardiomyopathy in a family with autosomal dominant striate palmoplantar keratoderma and woolly hair associated with a novel insertion mutation in desmoplakin. J Invest Dermatol. 2006;126(7):1651-4. doi:10.1038/sj.jid.5700291.Norgett EE, Lucke TW, Bowers B, et al. Early death from cardiomyopathy in a family with autosomal dominant striate palmoplantar keratoderma and woolly hair associated with a novel insertion mutation in desmoplakin. J Invest Dermatol. 2006;126(7):1651-4. doi:10.1038/sj.jid.5700291.Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000;9:2761-6.Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000;9:2761-6.Drezner JA, Fudge J, Harmon KG, et al. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25(4):408-15. doi:10.3122/jabfm.2012.04.110225.Drezner JA, Fudge J, Harmon KG, et al. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25(4):408-15. doi:10.3122/jabfm.2012.04.110225.Williams T, Machann W, Kuhler L, et al. Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma.Clin Res Cardiol. 2011;100(12):1087-93. doi:10.1007/s00392-011-0345-9.Williams T, Machann W, Kuhler L, et al. Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma.Clin Res Cardiol. 2011;100(12):1087-93. doi:10.1007/s00392-011-0345-9.Stollberger C, Blazek G, Gessner M, et al. Age-dependency of cardiac and neuromuscular findings in adults with left ventricular hypertrabeculation/noncompaction. Am J Cardiol. 2015;115(9):1287-92. doi:10.1016/j.amjcard.2015.02.014.Stollberger C, Blazek G, Gessner M, et al. Age-dependency of cardiac and neuromuscular findings in adults with left ventricular hypertrabeculation/noncompaction. Am J Cardiol. 2015;115(9):1287-92. doi:10.1016/j.amjcard.2015.02.014.Bharucha T, Lee KJ, Daubeney PE, et al. Sudden death in childhood cardiomyopathy: results from a long-term national population-based study. J Am Coll Cardiol. 2015;65(21):2302- 10. doi:10.1016/j.jacc.2015.03.552.Bharucha T, Lee KJ, Daubeney PE, et al. Sudden death in childhood cardiomyopathy: results from a long-term national population-based study. J Am Coll Cardiol. 2015;65(21):2302- 10. doi:10.1016/j.jacc.2015.03.552.Maleic I, Buljevic B. Arrhythmogenic right ventricular cardiomyopathy, Naxos island disease and Carvajal syndrome. Central European Journal of Paediatrics. 2017;13(2):93- 106. doi:10.5457/p2005-114.177.Maleic I, Buljevic B. Arrhythmogenic right ventricular cardiomyopathy, Naxos island disease and Carvajal syndrome. Central European Journal of Paediatrics. 2017;13(2):93- 106. doi:10.5457/p2005-114.177.Baykan A, Olgar S, Argun M, et al. Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature. Anatol J Cardiol. 2015;15(5):404-8. doi:10.5152/akd.2014.5413.Baykan A, Olgar S, Argun M, et al. Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature. Anatol J Cardiol. 2015;15(5):404-8. doi:10.5152/akd.2014.5413.Rasmussen TB, Hansen J, Nissen PH, et al. Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms. Clin Genet. 2013;84(1):20-30. doi:10.1111/cge.12056.Rasmussen TB, Hansen J, Nissen PH, et al. Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms. Clin Genet. 2013;84(1):20-30. doi:10.1111/cge.12056.Alcalai R, Metzger S, Rosenheck S, et al. A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair. J. Am. Coll. Cardiol. 2003;42:319-27. doi:10.1016/S0735-1097(03)00628-4.Alcalai R, Metzger S, Rosenheck S, et al. A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair. J. Am. Coll. Cardiol. 2003;42:319-27. doi:10.1016/S0735-1097(03)00628-4.Arbustini E, Narula N, Dec WG, et al. The MOGE(S) Classification for a phenotype- genotype nomenclature of cardiomyopathy endorsed by the World Heart Federation. J Am Coll Cardiol. 2013;62(22):2046-72. doi:10.1016/j.jacc.2013.08.1644.Arbustini E, Narula N, Dec WG, et al. The MOGE(S) Classification for a phenotype- genotype nomenclature of cardiomyopathy endorsed by the World Heart Federation. J Am Coll Cardiol. 2013;62(22):2046-72. doi:10.1016/j.jacc.2013.08.1644.Herbert Pratt C, Potter CS, Fairfield H, et al. DSP rul: a spontaneous mouse mutation in desmoplakin as a model of Carvajal-Huerta syndrome. Exp Mol Pathol. 2015;98(2):164- 72. doi:10.1016/j.yexmp.2015.01.015.Herbert Pratt C, Potter CS, Fairfield H, et al. DSP rul: a spontaneous mouse mutation in desmoplakin as a model of Carvajal-Huerta syndrome. Exp Mol Pathol. 2015;98(2):164- 72. doi:10.1016/j.yexmp.2015.01.015.Armstrong DK, McKenna KE, Purkis PE, et al. Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum. Molec. Genet. 1999;8:143-48.Armstrong DK, McKenna KE, Purkis PE, et al. Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum. Molec. Genet. 1999;8:143-48.Uzumcu A, Norgett EE, Dindar A, et al. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome. J Med. Genet. 2006;43(2):e5. doi:10.1136/jmg.2005.032904.Uzumcu A, Norgett EE, Dindar A, et al. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome. J Med. Genet. 2006;43(2):e5. doi:10.1136/jmg.2005.032904.Pigors M, Schwieger-Briel A, Cosgarea R, et al. Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy. Acta Derm. Venereol. 2015;95:337-40. doi:10.2340/00015555-1974.Pigors M, Schwieger-Briel A, Cosgarea R, et al. Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy. Acta Derm. Venereol. 2015;95:337-40. doi:10.2340/00015555-1974.Kang H, Weiss TM, Bang I, et al. Structure of the Intermediate Filament-Binding Region of Desmoplakin. PLoS ONE 2016;11:e0147641. doi:10.1371/journal.pone.0147641.Kang H, Weiss TM, Bang I, et al. Structure of the Intermediate Filament-Binding Region of Desmoplakin. PLoS ONE 2016;11:e0147641. doi:10.1371/journal.pone.0147641.

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