Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives

Abstract

Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

Resumo

A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Keywords

Charcot-Marie-Tooth disease - Hereditary Sensory and Motor Neuropathy - Peripheral Nervous System diseases

Palavras-chave

Doença de Charcot-Marie-Tooth - Neuropatia Hereditária Motora e Sensorial - Doenças do Sistema Nervoso Periférico

Authors' Contributions

EBUC: conceptualization, data collection, writing of the original manuscript; RCCL: conceptualization, data collection, critical review; WMJ: conceptualization, supervision, critical review; OJMN: conceptualization, supervision, critical review, project administration.

Publikationsverlauf

Eingereicht: 30. Oktober 2022

Angenommen: 16. März 2023

Artikel online veröffentlicht:
23. August 2023

• References

• 1 Rossor AM, Carr AS, Devine H. et al. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis. J Neurol Neurosurg Psychiatry 2017; 88 (10) 846-863
• 2 Laurá M, Pipis M, Rossor AM, Reilly MM. Charcot-Marie-Tooth disease and related disorders: an evolving landscape. Curr Opin Neurol 2019; 32 (05) 641-650
• 3 Saporta MA. Charcot-Marie-Tooth disease and other inherited neuropathies. Continuum (Minneap Minn) 2014; 20 (5 Peripheral Nervous System Disorders): 1208-1225
• 4 Murphy SM, Laura M, Fawcett K. et al. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry 2012; 83 (07) 706-710
• 5 Yoshimura A, Yuan JH, Hashiguchi A. et al. Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan. J Neurol Neurosurg Psychiatry 2019; 90 (02) 195-202
• 6 Vance JM, Nicholson GA, Yamaoka LH. et al. Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17. Exp Neurol 1989; 104 (02) 186-189
• 7 Juneja M, Burns J, Saporta MA, Timmerman V. Challenges in modelling the Charcot-Marie-Tooth neuropathies for therapy development. J Neurol Neurosurg Psychiatry 2019; 90 (01) 58-67
• 8 Rudnik-Schöneborn S, Auer-Grumbach M, Senderek J. Charcot-Marie-Tooth disease and hereditary motor neuropathies – Update 2020. Med Genetik 2020; 32 (03) 207-219
• 9 Cortese A, Wilcox JE, Polke JM. et al. Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease. Neurology 2020; 94 (01) e51-e61
• 10 Volodarsky M, Kerkhof J, Stuart A. et al. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J Med Genet 2021; 58 (04) 284-288
• 11 Rossor AM, Tomaselli PJ, Reilly MM. Recent advances in the genetic neuropathies. Curr Opin Neurol 2016; 29 (05) 537-548
• 12 Pipis M, Rossor AM, Laura M, Reilly MM. Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Nat Rev Neurol 2019; 15 (11) 644-656
• 13 Uchôa Cavalcanti EB, Santos Sde L, Martins CES. et al. Charcot-Marie-Tooth disease: Genetic profile of patients from a large Brazilian neuromuscular reference center. J Peripheral Nervous System 2021; 26 (03) 290-297
• 14 Bis-Brewer DM, Fazal S, Züchner S. Genetic modifiers and non-Mendelian aspects of CMT. Brain Res 2020; 1726: 146459
• 15 Fridman V, Saporta MA. Mechanisms and Treatments in Demyelinating CMT. Neurotherapeutics 2021; 18 (04) 2236-2268
• 16 Miniou P, Fontes M. Therapeutic development in charcot marie tooth type 1 disease. Int J Mol Sci 2021; 22 (13) 6755
• 17 Longo PW, Pupo PP, Giorgi D. Possível parentesco entre as moléstias familiares com lesões predominantes na medula e moléstias familiares com lesões no neurônio periférico. Arq Neuropsiquiatr. 1943; 1 (01) 43-52
• 18 Deolindo Augusto de Nunes Couto. Clínica Neurológica. Rio de Janeiro: A Casa do Livro LTDA; 1944
• 19 Levy JA. Moléstia de Charcot-Marie-Tooth: conceito clínico-patológico atual. Arq Neuropsiquiatr. 1962; 20 (02) 131-136
• 20 Arruda WO, Comerlato EA, Scola RH, Silvado CES, Werneck LC. Hereditary motor and sensory neuropathy with congenital glaucoma. Report on a family. Arq Neuropsiquiatr 1999; 57 (2A): 190-194
• 21 de Freitas MRG, Nascimento OJM, de Freitas GR. Doença de Charcot-Marie-Tooth: estudo clínico em 45 pacientes. Arq Neuropsiquiatr 1995; 53 (3b): 545-551
• 22 Viegas Cde A. Doença de Charcot-Marie-Tooth associada a malformação de Klippel-Feil: registro de um caso e revisão da literatura. Arq Neuropsiquiatr 1980; 38 (02) 193-199
• 23 de Mattos JP, Martins WN. Amiotrofia neuro-medular de Charcot-Marie-Tooth associada a artrogripose multipla congenita: registro de um caso e revisão da literatura. Arq Neuropsiquiatr 1982; 40 (03) 281-288
• 24 Freitas MRG, Nascimento OJM, Chimelli L, de Freitas GR. Doença de Charcot-Marie-Tooth: estudo da biópsia do nervo sural em 41 pacientes. Arq Neuropsiquiatr 1995; 53 (3b): 560-569
• 25 Marques Jr W, Freitas MR, Nascimento OJM. et al. 17p duplicated Charcot-Marie-Tooth 1A: characteristics of a new population. J Neurol 2005; 252 (08) 972-979
• 26 Pasnoor M, Nascimento OJM, Trivedi J. et al. North America and South America (NA-SA) neuropathy project. Int J Neurosci 2013; 123 (08) 563-567
• 27 Padilha JPD, Brasil CS, Hoefel AML. et al. Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies. Clin Genet 2020; 98 (02) 185-190
• 28 Figueiredo FB, Silva Jr WA, Giuliatti S. et al. GDAP1 mutations are frequent among Brazilian patients with autosomal recessive axonal Charcot-Marie-Tooth disease. Neuromuscul Disord 2021; 31 (06) 505-511
• 29 Ribiere C, Bernardin M, Sacconi S. et al. Pain assessment in Charcot-Marie-Tooth (CMT) disease. Ann Phys Rehabil Med 2012; 55 (03) 160-173
• 30 Laurà M, Hutton EJ, Blake J. et al. Pain and small fiber function in Charcot-Marie-Tooth disease type 1A. Muscle Nerve 2014; 50 (03) 366-371
• 31 Bjelica B, Peric S, Basta I. et al. Neuropathic pain in patients with Charcot-Marie-Tooth type 1A. Neurol Sci 2020; 41 (03) 625-630
• 32 Peretti A, Squintani G, Taioli F, Tagliapietra M, Cavallaro T, Fabrizi GM. Neuropathic pain in Charcot-Marie-Tooth disease: A clinical and laser-evoked potential study. Eur J Pain 2022; 26 (04) 929-936
• 33 Ramchandren S, Jaiswal M, Feldman E, Shy M. Effect of pain in pediatric inherited neuropathies. Neurology 2014; 82 (09) 793-797
• 34 Azevedo H, Costa H, Davidovich E, Pupe C, Nascimento OJM. Prevalence and characterization of pain in patients with Charcot-Marie-Tooth disease type 1A. Arq Neuropsiquiatr 2021; 79 (05) 415-419
• 35 Argov Z, de Visser M. What we do not know about pregnancy in hereditary neuromuscular disorders. Neuromuscul Disord 2009; 19 (10) 675-679
• 36 Hoff JM, Gilhus NE, Daltveit AK. Pregnancies and deliveries in patients with Charcot-Marie-Tooth disease. Neurology 2005; 64 (03) 459-462
• 37 Creigh PD, Herrmann DN. Charcot-Marie-Tooth Disease and Pregnancy. Neurological Diseases and PregnancyA Coordinated Care Model for Best Management. Oxford, UK: Oxford University Press; 2018
• 38 Bellina JH, Deming B. Charcot-Marie-Tooth disease and pregnancy: report of a case. J La State Med Soc 1973; 125 (11) 393-395
• 39 Pollock M, Nukada H, Kritchevsky M. Exacerbation of Charcot-Marie-tooth disease in pregnancy. Neurology 1982; 32 (11) 1311-1314
• 40 Pisciotta C, Calabrese D, Santoro L. et al; Italian CMT Network. Pregnancy in Charcot-Marie-Tooth disease: Data from the Italian CMT national registry. Neurology 2020; 95 (24) e3180-e3189
• 41 Brian Jr JE, Boyles GD, Quirk Jr JG, Clark RB. Anesthetic management for cesarean section of a patient with Charcot-Marie-Tooth disease. Anesthesiology 1987; 66 (03) 410-412
• 42 Rudnik-Schöneborn S, Thiele S, Walter MC. et al. Pregnancy outcome in Charcot-Marie-Tooth disease: results of the CMT-NET cohort study in Germany. Eur J Neurol 2020; 27 (08) 1390-1396
• 43 Leal Rde CC. Influência da gravidez sobre a neuropatia de pacientes com a doença de Charcot-Marie-Tooth tipo 1A. [Ribeirão Preto]: Universidade de São Paulo; 2016
• 44 Rudnik-Schöneborn S, Elbracht M. Charcot-Marie-Tooth neuropathy and pregnancy: General and specific issues. Med Genetik 2020;32(03):
• 45 Swan ER, Fuerst DR, Shy ME. Women and men are equally disabled by Charcot-Marie-Tooth disease type 1A. Neurology 2007; 68 (11) 873
• 46 Awater C, Zerres K, Rudnik-Schöneborn S. Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients. Eur J Obstet Gynecol Reprod Biol 2012; 162 (02) 153-159
• 47 Rudnik-Schöneborn S, Röhrig D, Nicholson G, Zerres K. Pregnancy and delivery in Charcot-Marie-Tooth disease type 1. Neurology 1993; 43 (10) 2011-2016
• 48 Betran AP, Ye J, Moller AB, Souza JP, Zhang J. Trends and projections of caesarean section rates: global and regional estimates. BMJ Glob Health 2021; 6 (06) e005671
• 49 Grace J, El-Toukhy T, Scriven P. et al. Three hundred and thirty cycles of preimplantation genetic diagnosis for serious genetic disease: clinical considerations affecting outcome. BJOG 2006; 113 (12) 1393-1401
• 50 De Vos A, Sermon K, Van de Velde H. et al. Pregnancy after preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A. Mol Hum Reprod 1998; 4 (10) 978-984
• 51 Lee HS, Kim MJ, Ko DS, Jeon EJ, Kim JY, Kang IS. Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease. Clin Exp Reprod Med. The Korean Society for Reproductive Medicine 2013; 40: 163-168
• 52 De Vos A, Sermon K, De Rijcke M. et al. Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A. Mol Hum Reprod 2003; 9 (07) 429-435
• 53 Hatakeyama S, Suzuki J, Murakami T. et al. [Respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease: a case report]. Nihon Kokyuki Gakkai Zasshi. Japan 2000; 38 (08) 637-641
• 54 Osanai S, Akiba Y, Nakano H, Matsumoto H, Yahara O, Onodera S. Charcot-Marie-Tooth disease with diaphragmatic weakness. Intern Med 1992; 31 (11) 1267-1270
• 55 Sevilla T, Jaijo T, Nauffal D. et al. Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms of GDAP1-associated neuropathy. Brain 2008; 131 (Pt 11): 3051-3061
• 56 Nathanson BN, Yu DG, Chan CK. Respiratory muscle weakness in Charcot-Marie-Tooth disease. A field study. Arch Intern Med 1989; 149 (06) 1389-1391
• 57 de Carvalho Alcântara M, Nogueira-Barbosa MH, Fernandes RMF. et al. Respiratory dysfunction in Charcot-Marie-Tooth disease type 1A. J Neurol 2015; 262 (05) 1164-1171
• 58 Spiesshoefer J, Henke C, Kabitz HJ. et al. Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot-Marie-Tooth disease 1A. Journal of the Peripheral Nervous System. John Wiley & Sons. Ltd 2019; 24 (03) 283-293
• 59 Bussmann J, Storkebaum E. Molecular pathogenesis of peripheral neuropathies: insights from Drosophila models. Curr Opin Genet Dev 2017; 44: 61-73
• 60 Bosco L, Falzone YM, Previtali SC. Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies. Brain Sci 2021; 11 (09) 1237
• 61 Jerath NU, Shy ME. Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies. Biochim Biophys Acta 2015; 1852 (04) 667-678
• 62 Chumakov I, Milet A, Cholet N. et al. Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy. Orphanet J Rare Dis 2014; 9 (01) 201
• 63 Prukop T, Stenzel J, Wernick S. et al. Early short-term PXT3003 combinational therapy delays disease onset in a transgenic rat model of Charcot-Marie-Tooth disease 1A (CMT1A). PLoS One 2019; 14 (01) e0209752
• 64 Attarian S, Dubourg O, Funalot B. et al. A phase II randomized, placebo-controlled multicenter clinical trial of three doses of PXT3003 in 80 adult patients with CMT1A treated for 1 year. J Peripher Nerv Syst 2013; 18: CC
• 65 Attarian S, Young P, Brannagan TH. et al. A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A. Orphanet J Rare Dis 2021; 16 (01) 433
• 66 Fledrich R, Abdelaal T, Rasch L. et al. Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. Nat Commun 2018; 9 (01) 3025
• 67 Visigalli D, Capodivento G, Basit A. et al. Exploiting Sphingo- and Glycerophospholipid Impairment to Select Effective Drugs and Biomarkers for CMT1A. Front Neurol 2020; 11: 903
• 68 Zhao HT, Damle S, Ikeda-Lee K. et al. PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models. J Clin Invest 2018; 128 (01) 359-368
• 69 Lee JS, Lee JY, Song DW. et al. Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice. Nucleic Acids Res 2020; 48 (01) 130-140
• 70 Caillaud M, Msheik Z, Ndong-Ntoutoume GMA. et al. Curcumin-cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress. Free Radic Biol Med 2020; 161: 246-262
• 71 Gautier B, Hajjar H, Soares S. et al. AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A. Nat Commun 2021; 12 (01) 2356
• 72 Bai Y, Treins C, Volpi VG. et al. Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice. Mol Neurobiol 2022; 59 (07) 4159-4178
• 73 Mones S, Gess B, Bordignon B. et al. CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors. Orphanet J Rare Dis 2015; 10 (01) 56
• 74 Shy ME, Siskind C, Swan ER. et al. CMT1X phenotypes represent loss of GJB1 gene function. Neurology 2007; 68 (11) 849-855
• 75 Kagiava A, Karaiskos C, Richter J. et al. Intrathecal gene therapy in mouse models expressing CMT1X mutations. Hum Mol Genet 2018; 27 (08) 1460-1473
• 76 Kagiava A, Richter J, Tryfonos C. et al. Gene replacement therapy after neuropathy onset provides therapeutic benefit in a model of CMT1X. Hum Mol Genet 2019; 28 (21) 3528-3542
• 77 Chandhok G, Lazarou M, Neumann B. Structure, function, and regulation of mitofusin-2 in health and disease. Biol Rev Camb Philos Soc 2018; 93 (02) 933-949
• 78 Takahashi R, Ikeda T, Hamaguchi A, Iwasa K, Yamada M. Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation. Intern Med 2012; 51 (07) 791-793
• 79 Mourier A, Motori E, Brandt T. et al. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol 2015; 208 (04) 429-442
• 80 Rocha AG, Franco A, Krezel AM. et al. MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science 2018; 360 (6386): 336-341