Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press19610.17650/2222-8721-2017-7-1-37-42ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯAnalysis of primary diagnostics of hereditary motor and sensory neuropathies in the Republic of BashkortostanАнализ первичной диагностики наследственных моторно-сенсорных нейропатий в Республике БашкортостанSaifullinaE. V.СайфуллинаЕ. В.
Russian Federation

Department of Neurology with Courses on Neurosurgery and Medical Genetics

3 Lenina St., Ufa 450008, Republic of Bashkortostan, Russia

Кафедра неврологии с курсами нейрохирургии и медицинской генетики

Россия, Республика Башкортостан, 450008 Уфа, ул. Ленина, 3

riledin@mail.ruMagzhanovR. V.МагжановР. В.
Russian Federation

Department of Neurology with Courses on Neurosurgery and Medical Genetics

3 Lenina St., Ufa 450008, Republic of Bashkortostan, Russia

Кафедра неврологии с курсами нейрохирургии и медицинской генетики

Россия, Республика Башкортостан, 450008 Уфа, ул. Ленина, 3

KhidiiatovaI. M.ХидиятоваИ. М.
Russian Federation

71 Oktyabrya Prospekt, Ufa 450054, Republic of Bashkortostan, Russia

Россия, Республика Башкортостан, 450054 Уфа, проспект Октября, 71

KhusnutdinovaE. K.ХуснутдиноваЭ. К.
Russian Federation

71 Oktyabrya Prospekt, Ufa 450054, Republic of Bashkortostan, Russia

Россия, Республика Башкортостан, 450054 Уфа, проспект Октября, 71

Bashkir State Medical University, Ministry of Health of RussiaФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииInstitute of Biochemistry and Genetics of the Ufa Scientific Center of the RASФГБУН «Институт биохимии и генетики Уфимского научного центра РАН»070520177137420705201707052017Copyright ©; 2017, Saifullina E.V., Magzhanov R.V., Khidiiatova I.M., Khusnutdinova E.K.Copyright ©; 2017, Сайфуллина Е.В., Магжанов Р.В., Хидиятова И.М., Хуснутдинова Э.К.2017Saifullina E.V., Magzhanov R.V., Khidiiatova I.M., Khusnutdinova E.K.Сайфуллина Е.В., Магжанов Р.В., Хидиятова И.М., Хуснутдинова Э.К.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/196

Background. Hereditary motor and sensory neuropathies (HMSN, Charcot–Marie–Tooth disease) form genetically heterogenous and clinically polymorphic group of diseases which predominantly affect peripheral nervous system. Correct primary diagnostics of these diseases is a starting point for planning subsequent molecular and genetic diagnostics.

Objective. Analysis of primary diagnostics of HMSN for subsequent improvement of specialized medical and genetic help for patients and their families.

Materials and methods. We analyzed 260 primary diagnoses of patients referred to a neurogeneticist for consultation and registered in the Genetics Consultation Clinic with the diagnosis of HMSN between 1970 and 2016.

Results. A total of 17 variants of referral diagnoses of patients with HMSN were identified. They can be divided into 3 subgroups: hereditary diseases of the nervous and neuromuscular systems, other diseases of the nervous system, diseases of other systems. A correct diagnosis was listed in a little more than half (58.1 %) of all cases of primary referrals. The most common (10.8 %) erroneous referral diagnosis of patients with HMSN was Friedreich’s ataxia. Most of erroneous referral diagnoses could be confidently ruled out at the stage of primary clinical diagnosis and after electroneuromyography. Altogether, in the observed period percentage of correct referral diagnoses increased while the specter of erroneous diagnoses decreased significantly which attests to increased doctors’ awareness of HMSN.

Conclusion. In order to improve HMSN diagnostics doctors should pay more attention to analysis of family medical history and perform a clinical examination of all proband’s available relatives.

hereditary motor and sensory neuropathyCharcot–Marie–Tooth diseasedifferential diagnosisнаследственная моторно-сенсорная нейропатияболезнь Шарко–Мари–Тутадифференциальная диагностика1. Dyck P. J., Chance P., Lebo R., Carney J. A. Hereditary motor and sensory neuropathies. In book: Peripheral Neuropathy. Eds. P. J. Dyck, P. K. Thomas, J. W. Griffin et al. Philadelphia: W. B. Saunders Company, 1993. Pp. 1094–1136.Dyck P. J., Chance P., Lebo R., Carney J. A. Hereditary motor and sensory neuropathies. In book: Peripheral Neuropathy. Eds. P. J. Dyck, P. K. Thomas, J. W. Griffin et al. Philadelphia: W. B. Saunders Company, 1993. Pp. 1094–1136.2. Bird T. D. Charcot–Marie–Tooth hereditary neuropathy overview. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1358/.Bird T. D. Charcot–Marie–Tooth hereditary neuropathy overview. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1358/.3. Hereditary motor sensory neuropathies (HMSN, CMT). Available at: http://neuromuscular.wustl.edu/time/hmsn.html (дата обращения 31.08.2016).Hereditary motor sensory neuropathies (HMSN, CMT). Available at: http://neuromuscular.wustl.edu/time/hmsn.html (дата обращения 31.08.2016).4. Rossor A. M., Evans M. R., Reilly M. M. A practical approach to the genetic neuropathies. Pract Neurol 2015;15(3):187–98. DOI: 10.1136/practneurol-2015-001095. PMID: 25898997.Rossor A. M., Evans M. R., Reilly M. M. A practical approach to the genetic neuropathies. Pract Neurol 2015;15(3):187–98. DOI: 10.1136/practneurol-2015-001095. PMID: 25898997.5. Harding A. E., Thomas P. K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 1980;103(2):259–80. DOI: 10.1093/brain/103.2.259. PMID: 7397478.Harding A. E., Thomas P. K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 1980;103(2):259–80. DOI: 10.1093/brain/103.2.259. PMID: 7397478.6. Nicholson G., Myers S. Intermediate forms of Charcot–Marie–Tooth neuropathy: a review. Neuromolecular Med 2006;8(1–2):123–30. DOI: 10.1385/NMM:9:1. PMID: 16775371.Nicholson G., Myers S. Intermediate forms of Charcot–Marie–Tooth neuropathy: a review. Neuromolecular Med 2006;8(1–2):123–30. DOI: 10.1385/NMM:9:1. PMID: 16775371.7. Timmerman V., Strickland A. V., Züchner S. Genetics of Charcot–Marie– Tooth (CMT) disease within the frame of the human genome project success. Genes (Basel) 2014;5(1):13–32. DOI: 10.3390/genes5010013. PMID: 24705285.Timmerman V., Strickland A. V., Züchner S. Genetics of Charcot–Marie– Tooth (CMT) disease within the frame of the human genome project success. Genes (Basel) 2014;5(1):13–32. DOI: 10.3390/genes5010013. PMID: 24705285.8. Дадали Е.Л., Макаов А.Х.-М., Галкина В.А. и др. Наследственная моторно-сенсорная нейропатия, обусловленная мутацией в гене NEFL, в семье из Карачаево-Черкессии. Нервно-мышечные болезни 2016;6(2):47–51. [Dadali Е.L., Маkаоv А.Кh.-М., Galkina А.V. et al. Hereditary motor and sensory neuropathy, caused by mutations in the NEFL gene in a family from Karachaevo-Cherkessia. Nervno-myshechnye bolezni = Neuromuscular DiseasesДадали Е.Л., Макаов А.Х.-М., Галкина В.А. и др. Наследственная моторно-сенсорная нейропатия, обусловленная мутацией в гене NEFL, в семье из Карачаево-Черкессии. Нервно-мышечные болезни 2016;6(2):47–51. [Dadali Е.L., Маkаоv А.Кh.-М., Galkina А.V. et al. Hereditary motor and sensory neuropathy, caused by mutations in the NEFL gene in a family from Karachaevo-Cherkessia. Nervno-myshechnye bolezni = Neuromuscular Diseases2016;6(2):47–51. (In Russ.)]. DOI: 10.17650/2222-8721-2016-6-2-47-51.;6(2):47–51. (In Russ.)]. DOI: 10.17650/2222-8721-2016-6-2-47-51.9. Крупина Н. Б., Магжанов Р. В., Сайфуллина Е. В. База данных по наследственным моторно-сенсорным нейропатиям Республики Башкортостан. Здравоохранение и медицинская техника 2006;(3):46. [Krupina N. B., Magzhanov R. V., Saifullina E. V. Database of hereditary motor and sensory neuropathies of the Republic of Bashkortostan. Zdravookhranenie i meditsinskaya tekhnika = Healthcare and Medical Devices 2006;(3):46. (In Russ.)].Крупина Н. Б., Магжанов Р. В., Сайфуллина Е. В. База данных по наследственным моторно-сенсорным нейропатиям Республики Башкортостан. Здравоохранение и медицинская техника 2006;(3):46. [Krupina N. B., Magzhanov R. V., Saifullina E. V. Database of hereditary motor and sensory neuropathies of the Republic of Bashkortostan. Zdravookhranenie i meditsinskaya tekhnika = Healthcare and Medical Devices 2006;(3):46. (In Russ.)].10. Julião O. F. Étudesur la névritehypertrophique progressive de Déjerine-Sottas. Arq Neuropsiquiatr 1952;10(2):221–46. DOI: 10.1590/s0004-282x1952000200012. PMID: 12987354.Julião O. F. Étudesur la névritehypertrophique progressive de Déjerine-Sottas. Arq Neuropsiquiatr 1952;10(2):221–46. DOI: 10.1590/s0004-282x1952000200012. PMID: 12987354.11. Roa B. B., Dyck P. J., Marks H. G. et al. Dejerine–Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet 1993;5(3):269–73. DOI: 10.1038/ng1193-269. PMID: 8275092.Roa B. B., Dyck P. J., Marks H. G. et al. Dejerine–Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet 1993;5(3):269–73. DOI: 10.1038/ng1193-269. PMID: 8275092.12. Hayasaka K., Himoro M., Sawaishi Y. et al. De novo mutation of the myelin P0 gene in Dejerine–Sottas disease (hereditary motor and sensory neuropathy type III). Nat Genet 1993;5(3):266–8. DOI: 10.1038/ng1193-266. PMID: 7506095.Hayasaka K., Himoro M., Sawaishi Y. et al. De novo mutation of the myelin P0 gene in Dejerine–Sottas disease (hereditary motor and sensory neuropathy type III). Nat Genet 1993;5(3):266–8. DOI: 10.1038/ng1193-266. PMID: 7506095.13. Timmerman V., de Jonghe P., Ceuterick C. et al. Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype. Neurology 1999;52(9):1827. DOI: 10.1212/wnl.52.9.1827. PMID: 10371530.Timmerman V., de Jonghe P., Ceuterick C. et al. Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype. Neurology 1999;52(9):1827. DOI: 10.1212/wnl.52.9.1827. PMID: 10371530.14. Boerkoel C. F., Takashima H., Stankiewicz P. et al. Periaxin mutations cause recessive Dejerine–Sottas neuropathy. Am J Hum Genet 2001;68(2):325–33. DOI: 10.1086/318208. PMID: 11133365.Boerkoel C. F., Takashima H., Stankiewicz P. et al. Periaxin mutations cause recessive Dejerine–Sottas neuropathy. Am J Hum Genet 2001;68(2):325–33. DOI: 10.1086/318208. PMID: 11133365.15. Planté-Bordeneuve V., Guiochon-Mantel A., Lacroix C. et al. The Roussy-Lévy family: from the original description to the gene. Ann Neurol 1999;46(5):770–3. PMID: 10553995.Planté-Bordeneuve V., Guiochon-Mantel A., Lacroix C. et al. The Roussy-Lévy family: from the original description to the gene. Ann Neurol 1999;46(5):770–3. PMID: 10553995.16. Parman Y., Battaloglu E., Baris I. et al. Clinicopathological and genetic study of early- onset demyelinating neuropathy. Brain 2004;127(Pt 11):2540–50. DOI: 10.1093/brain/awh275. PMID: 15469949.Parman Y., Battaloglu E., Baris I. et al. Clinicopathological and genetic study of early- onset demyelinating neuropathy. Brain 2004;127(Pt 11):2540–50. DOI: 10.1093/brain/awh275. PMID: 15469949.17. Bidichandani S. I., Delatycki M. B. Friedreich ataxia. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. PMID: 20301458.Bidichandani S. I., Delatycki M. B. Friedreich ataxia. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. PMID: 20301458.18. Fink J. K. Hereditary spastic paraplegia overview. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. PMID: 20301682.Fink J. K. Hereditary spastic paraplegia overview. In book: Gene Reviews. Eds. R. A. Pagon, M. P. Adam, H. H. Ardinger et al. Seattle: University of Washington, 1993. PMID: 20301682.19. Сайфуллина Е. В., Магжанов Р. В., Хидиятова И. М. и др. Клинический случай новой мутации в гене коннексина 32 в семье с Х-сцепленной наследственной моторно- сенсорной нейропатией. Неврологический журнал 2011;(4):45–7. [Saifullina E. V., Magzhanov R. V., Khidiiatova I. M. et al. Clinical case of a new mutation in connexin 32 gene in a family with X-linked hereditary motor and sensory neuropathy. Nevrologicheskiy zhurnal = Neurological Journal 2011;(4):45–7. (In Russ.)].Сайфуллина Е. В., Магжанов Р. В., Хидиятова И. М. и др. Клинический случай новой мутации в гене коннексина 32 в семье с Х-сцепленной наследственной моторно- сенсорной нейропатией. Неврологический журнал 2011;(4):45–7. [Saifullina E. V., Magzhanov R. V., Khidiiatova I. M. et al. Clinical case of a new mutation in connexin 32 gene in a family with X-linked hereditary motor and sensory neuropathy. Nevrologicheskiy zhurnal = Neurological Journal 2011;(4):45–7. (In Russ.)].20. Сайфуллина Е. В., Магжанов Р. В., Хидиятова И. М. и др. Клинико-генетическая характеристика пациентов с наследственными моторно-сенсорными невропатиями из Республики Башкортостан с мутациями в гене MFN2. Неврологический журнал 2013; (1):30–4. [Saifullina E. V., Magzhanov R. V., Khidiiatova I. M. et al. The clinical and genetic characteristics of patients with inherited motor and sensor neuropathy and gene MFN2 mutation in Republic of Bashkortostan. Nevrologicheskiy zhurnal = Neurological Journal 2013;(1):30–4. (In Russ.)]. DOI: 10.18821/1560-9545-2013-18-1-30-34.Сайфуллина Е. В., Магжанов Р. В., Хидиятова И. М. и др. Клинико-генетическая характеристика пациентов с наследственными моторно-сенсорными невропатиями из Республики Башкортостан с мутациями в гене MFN2. Неврологический журнал 2013; (1):30–4. [Saifullina E. V., Magzhanov R. V., Khidiiatova I. M. et al. The clinical and genetic characteristics of patients with inherited motor and sensor neuropathy and gene MFN2 mutation in Republic of Bashkortostan. Nevrologicheskiy zhurnal = Neurological Journal 2013;(1):30–4. (In Russ.)]. DOI: 10.18821/1560-9545-2013-18-1-30-34.21. Ionasescu V., Ionasescu R., Searby C. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot–Marie– Tooth neuropathy. Am J Med Genet 1996;63(3):486–91. DOI: 10.1002/(SICI)1096-8628 (19960614)63:3<486::AID- AJMG14>3.0. CO;2-I. PMID: 8737658.Ionasescu V., Ionasescu R., Searby C. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot–Marie– Tooth neuropathy. Am J Med Genet 1996;63(3):486–91. DOI: 10.1002/(SICI)1096-8628 (19960614)63:3<486::AID- AJMG14>3.0. CO;2-I. PMID: 8737658.22. Дадали Е. Л., Шаркова И. В., Федотов В. П. и др. Клинико-генетический анализ наследственной моторно-сенсорной нейропатии IX типа (НМСН IX). Медицинская генетика 2004;(5):235–41. [Dadali E. L., Sharkova I. V., Fedotov V. P. et al. Clinical and genetic analysis of type IX hereditary motor and sensory neuropathy (HMSN IX). Meditsinskaya genetika = Medical Genetics 2004;(5):235–41. (In Russ.)].Дадали Е. Л., Шаркова И. В., Федотов В. П. и др. Клинико-генетический анализ наследственной моторно-сенсорной нейропатии IX типа (НМСН IX). Медицинская генетика 2004;(5):235–41. [Dadali E. L., Sharkova I. V., Fedotov V. P. et al. Clinical and genetic analysis of type IX hereditary motor and sensory neuropathy (HMSN IX). Meditsinskaya genetika = Medical Genetics 2004;(5):235–41. (In Russ.)].23. Irobi J., De Jonghe P., Timmerman V. Molecular genetics of distal hereditary motor neuropathies. Hum Mol Genet 2004; 13:195–202. DOI: 10.1093/hmg/ddh226. PMID: 15358725.Irobi J., De Jonghe P., Timmerman V. Molecular genetics of distal hereditary motor neuropathies. Hum Mol Genet 2004; 13:195–202. DOI: 10.1093/hmg/ddh226. PMID: 15358725.