Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector26910.17816/psaic269ReviewsОбзорыUnknownMyotonic dystrophy type 2Миотоническая дистрофия 2-го типаRudenskayaG. E.РуденскаяГ. E.
Russian Federation
geruden@gmail.comPolyakovA. V.ПоляковA. В.
Russian Federation
geruden@gmail.comResearch Centre for Medical Genetics, Russian Academy of Medical SciencesФГБУ «Медико-генетический научный центр» РАМН1006201262556002022017Copyright ©; 2012, Rudenskaya G.E., Polyakov A.V.Copyright ©; 2012, Rudenskaya G.E., Polyakov A.V.2012Rudenskaya G.E., Polyakov A.V.Rudenskaya G.E., Polyakov A.V.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/269

Myotonic dystrophy, type 2 (DM2) is an autosomal dominant disorder caused by expansion of the CCTG repeats in the zinkfinger protein-9 gene (ZNF9). It has been clinically reported in the middle 1990th. DM2 is less frequent than “classic” DM1, yet is relatively common, mostly in Europeans. Like DM1, DM2 is a multisystem disorder, and main distinctions from DM1 are: relatively late onset, proximal character of myopathy, less severe myotonia, presence of myalgia, etc. Clinical features complicate the diagnosis, and a number of cases cannot be identifiedon time. In the Research Centre for Medical Genetics the DNA diagnostics of DM2 is now available, and several cases have been confirmed molecularly.

Миотоническая дистрофия 2-го типа (ДМ2) – аутосомно-доминантная болезнь, связанная с экспансией 4-нуклеотидных повторов «цитозин-цитозин-тимин-гуанин» (ЦЦТГ) в гене ZNF9. Клинически ДМ2 описана в середине 1990-х гг., молекулярно-генетическая природа установлена в начале 2000-х гг. ДМ2 встречается реже, чем ДМ1, однако достаточно распространена у европейцев. В клинической картине преобладает сходство с ДМ1, но есть существенные отличия: более позднее начало, проксимальный характер миопатии, менее выраженная миотония, наличие миалгии и др. Клинические особенности затрудняют диагностику, ряд случаев своевременно не выявляется. В МГНЦ РАМН проводится ДНК-диагностика ДМ2, подтверждены на молекулярном уровне несколько случаев данного заболевания.

myotonic dystrophy type 2ZNF9 (CNBP1) geneCCTG repeatsproximal myotonic myopathymyalgiamultisystem involvementмиотоническая дистрофия 2-го типаген ZNF9повторы ЦЦТГпроксимальная миотоническая миопатиямиалгиямультисистемное поражениеШнайдер Н.А., Козулина Е.А., Дмитренко Д.В. Клинико-генетическая гетерогенность дистрофической миотонии: обзор литературы. Международн. неврологич. журн. 2007; 3 http://neurology. mif-ua.com/archive/issue-109/-155.Abbruzzese C., Krahe R., Liguori M. et al. Myotonic dystrophy phenotype without expansion of (CTG)n repeat: an entity distinct from proximal myotonic myopathy (PROMM)? J. Neurol. 243: 715-721, 1996. [PubMed: 8923304].Auvinen S., Suominen T., Hannonen P. et al. Myotonic dystrophy type 2 found in two of sixty-three persons diagnosed as having fibromyalgia. Arthr. Rheum. 2008; 58: 3627–3731.Bachinski L.L., Czernuszewicz T., Ramagli L.S. et al. Premutation allele pool in myotonic dystrophy type 2. Neurology 72: 490–497, 2009. [PubMed: 19020295]Bachinski L., Udd B., Meola G. et al. Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect. Am. J. Hum. Genet. 2003; 73: 835–848.Coenen M., Tieleman A., Schijvenaars M. et al. Dutch myotonic dystrophy type 2 patients and a North-African DM2 family carry the common European founder haplotype. Eur. J. Hum. Genet. 2011; 19: 567–570.Day J., Ricker K., Jacobsen J. et al. Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. Neurology 2003; 60: 657–664.Day J., Roelofs R., Leroy B. et al. Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2). Neuromusc. Disord. 1999; 9: 19–27.Eger K., Schulte-Mattler W., Zierz S. Proximal myotonic myopathy (PROMM). Clinical variability within a family. Nervenarzt 1997; 68: 839–844.Galeeva N., Rudenskaya G., Dadaly E., Polyakov A. Myotonic dystrophy type 2 in Russian families. Eur. J. Hum. Genet. 2010; 8 (Suppl. 1): 330.George A., Schneider-Gold C., Zier S. et al. Musculoskeletal pain in patients with myotonic dystrophy type 2. Arch. Neurol. 2004; 61: 1938–1942.Hund E., Jansen O., Koch M. et al. Proximal myotonic myopathy with MRI white matter abnormalities of the brain. Neurology 1997; 48: 33–37. 59 НАУЧНЫЙ ОБЗОР Миотоническая дистрофия 2-го типаKornblum C., Lutterbey G., Bogdanow M. et al. Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2: a whole body highfield MRI study. J. Neurol. 2006; 253: 753–761.Kruse B., Gal A. Talipes equinovarus as leading symptom of congenital myotonic dystrophy type 2. Muscle Nerve 2011; 43: 768.Kruse B., Wöhrle D., Steinbach P. et al. Does proximal myotonic myopathy show anticipation? Hum. Mutat. 2008; 29: E100-102.Lamont P.J., Jacob R.L., Mastaglia F.L., Laing N.G. An expansion in the ZNF9 gene causes PROMM in a previously described family with an incidental CLCN1 mutation. J. Neurol. Neurosurg. Psychiatry 2004; 75: 343.Liquori C., Ikeda Y., Weatherspoon M. et al. Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract. Am. J. Hum. Genet. 2003; 73: 849–862.Liquori C., Ricker K., Moseley M. et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001; 293: 864–867.Logigian E., Ciafaloni E., Quinn L.C. Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 2007; 35: 479–485.Mastaglia F., Harker N., Phillips B.A. et al. Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation. J. Neurol. Neurosurg. Psychiatry 1998; 64: 543–547.Maurage C., Udd B., Ruchoux M. et al. Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease. Neurology 2005; 65: 1636–1638.Meola G., Sansone V., Rotondo G. et al. PROMM in Italy: clinical and biomolecular findings. Acta Myol. 1998; 2: 21–26.Merlini L., Sabatelli P., Columbaro M. et al. Hyper-CK-emia as the sole manifestation of myotonic dystrophy type 2. Muscle Nerve 2005; 31: 764–767.Milone M., Batish S., Daube J.Myotonic dystrophy type 2 with focal asymmetric muscle weakness and no electrical myotonia. Muscle Nerve 2009; 39: 383–385.Minnerop M., Luders E., Specht K. et al. Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2. J. Neurol. 2008; 255: 1904–1909.Newman B., Meola G., O’Donovan D. et al. Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy. Neuromusc. Disord. 1999; 9: 144–149.OMIM http://www.ncbi.nlm.nih.gov.Pisani V., Panico M.B., Terracciano C. et al. Preferential central nucleation of type 2 myofibers is an invariable feature of myotonic dystrophy type 2. Muscle Nerve 2008; 38: 1405–1411.Raheem O., Olufemi S., Bachinski L. et al.Mutant (CCTG)n expansion causes abnormal expression of zinc finger protein 9 (ZNF9) in myotonic dystrophy type 2. Am. J. Pathol. 2010; 177: 3025–3036.Ranum L., Rasmussen P., Ben Ranum L. et al. Genetic mapping of a second myotonic dystrophy locus. Nature Genet. 1998; 19: 196–198.Renard D., Rivier F., Dimeglio A., Labauge P. Congenital talipes equinovarus associated with myotonic dystrophy type 2. Muscle Nerve 2010; 42: 457.Ricker K., Koch M., Lehmann-Horn F. et al. Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. Neurology 1994; 44: 1448–1452.Ricker K. Myotonic dystrophy and proximal myotonic myopathy. J. Neurol. 1999; 246: 334–338.Romeo V., Pegoraro E., Ferrati C. et al. Brain involvement in myotonic dystrophies: neuroimaging and neuropsychological comparative study in DM1 and DM2. J. Neurol. 2010; 257: 1246–1255.Rudnik-Schöneborn S., Schaupp M., Lindner A. et al. Brugada-like cardiac disease in myotonic dystrophy type 2: report of two unrelated patients. Eur. J. Neurol. 2011; 18: 191–194.Rudnik-Schöneborn S., Schneider-Gold C., Raabe U. et al. Outcome and effect of pregnancy in myotonic dystrophy type 2. Neurology 2006; 66: 579–580.Saito T., Amakusa Y., Kimura T. et al. Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families. Neurogenetics 2008; 9: 61–63.Sansone V., Gandossini S., Cotelli M. et al. Cognitive impairment in adult myotonic dystrophies: a longitudinal study. Neurol. Sci. 2007; 28: 9–15.Santoro M., Modoni A., Masciullo M. et al. Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/ adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2). Exp. Mol. Pathol. 2010; 89: 158–168.Schneider C., Ziegler A., Ricker K. et al. Proximal myotonic myopathy: evidence for anticipation in families with linkage to chromosome 3q. Neurology 2000; 55: 383–388.Schoser B., Ricker K., Schneider-Gold C. et al. Sudden cardiac death in myotonic dystrophy type 2. Neurology 2004; 63: 2402–2404.Sun C., Henriksen O.A., Tranebjaerg L. Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM. Clin. Genet. 1999; 56: 457–461.Sun C., Van Ghelue M., Tranebjaerg L. et al. Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene. Clin. Genet. 2011 [Epub ahead of print].Suominen T., Bachinski L., Auvinen S. et al. Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. Eur. J. Hum. Genet. 2011; 19: 776–782.Suominen T., Schoser B., Raheem O. et al. High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2 patients from Finland and Germany. J. Neurol. 2008; 255: 1731–1736.Thornton C., Griggs R., Moxley R. et al. Myotonic dystrophy with no trinucleotide repeat expansion. Ann. Neurol. 1994; 35: 269–272.Tieleman A., den Broeder A., van de Logt A., van Engelen B. Strong association between myotonic dystrophy type 2 and autoimmune diseases. J. Neurol. Neurosurg. Psychiatry 2009; 80: 1293–1295.Tieleman A., Jenks K., Kalkman J. et al. High disease impact of myotonic dystrophy type 2 on physical and mental functioning. J. Neurol. 2011; Apr 3. [Epub ahead of print].Tieleman A., Knoop H., van de Logt A. et al. Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic dystrophy type 2. J. Neurol. Neurosurg. Psychiatry 2010; 81: 963–967.Tieleman A., Knuijt S., van Vliet J. et al. Dysphagia is present but mild in myotonic dystrophy type 2. Neuromusc. Disord. 2009; 19: 196–198.Tieleman A., van Vliet J., Jansen J. et al. Gastrointestinal involvement is frequent in myotonic dystrophy type 2. Neuromusc. Disord. 2008; 18: 646–649.Todd P., Paulson H. RNA-mediated neurodegeneration in repeat expansion disorders. Ann. Neurol. 2010; 67: 291–300.Toth C., Dunham C., Suchowersky O. et al. Unusual clinical, laboratory, and muscle histopathological findings in a family with myotonic dystrophy type 2. Muscle Nerve 2007; 35: 259–264.Udd B., Meola G., Krahe R. et al.Myotonic dystrophy type 2 (DM2) and related disorders Neuromusc. Disord. 2011; 21: 443–450.Vihola A., Bassez G., Meola G. et al. Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. Neurology 2003; 60: 1854–1857.Wahbi K., Meune C., Bécane H. et al. Left ventricular dysfunction and cardiac arrhythmias are frequent in type 2 myotonic dystrophy: a case control study. Neuromusc. Disord. 2009; 19: 468–472.Washington University Neuromuscular Disease Database: http://neuromuscular.wustl.edu.Weber Y., Roebling R., Kassubek J. et al. Comparative analysis of brain structure, metabolism, and cognition in myotonic dystrophy 1 and 2. Neurology 2010; 74: 1108–1117.Young N., Daube J., Sorenson E., Milone M. Absent, unrecognized, and minimal myotonic discharges in myotonic dystrophy type 2. Muscle Nerve 2010; 41: 758–762