Hereditarne neuropatije uzrokovane mutacijama u genu koji kodira periferni mijelinski protein 22
Sažetak
Mutacije nastale u genu koji kodira periferni mijelinski protein 22 (PMP22) mogu se ispoljiti kao Charcot-Marie-Tooth-ova neuropatija 1A (CMT1A), u slučaju duplikacije, ili hereditarna neuropatija sa sklonošću ka kompresivnim paralizama (HNPP), u slučaju delecije ovog gena. U retkim slučajevima dolazi do tačkastih mutatija u PMP22 genu, pri čemu mogu nastati CMT1E i Déjerine-Sottas sindrom (DSS). CMT1A i HNPP predstavljaju najčešće nasledne neuropatije. CMT1A najčešće počinje u prve dve decenije života, a u kliničkoj slici su tipično prisutni izražena hipotrofija i slabost distalnih mišića sa ili bez ispada u senzibilitetu, deformacije stopala, poput ekskaviranog stopala (pes cavus) i "čekićastog" palca i sniženi ili odsutni mišićni refleksi. HNPP najčešće počinje između 20. i 30. godine života i ispoljava se u vidu tranzijentnih i rekurentnih fokalnih mononeuropatija sa motornim i senzitivnim simptomima i znacima u anatomskoj distrbuciji zahvaćenog nerva. Elektromioneurografskim ispitivanjem (EMNG) dobija se uniformno sniženje nervne provodljivosti kod CMT1A. EMNG nalaz kod HNPP ukazuje na difuznu, senzorimotornu, demijelinizacionu polineuropatija uz kondukcione blokove i temporalnu disperziju na mestima kompresije (medijalnog nerva u predelu ručja, ulnarnog nerva u predalu lakta i peronealnog nerva u predalu glave fibule). Terapija svih hereditarnih neuropatija, pa i CMT1A, se uglavnom svodi na simptomatsku terapiju, te od koristi mogu biti fizikalna terapija, korektivne hirurške intervencije, ortoze, kao i terapija neuropatkog bola. Terapija HNPP svodi se uglavnom na prevenciju kompresije nerva određenim aktivnostima i položajima tela. Zaštita laktova i kolena jastučićima može biti korisna kako bi se sprečila kompresija i povreda nerava, dok su u akutnoj fazi bolesti indikovani kortikosteroidna i fizikalna terapija. Razvoj terapija koje bi promenile tok bolesti je i dalje u toku.
Reference
1. Ramchandren S. Charcot-Marie-Tooth Disease and Other Genetic Polyneuropathies. Continuum (Minneap Minn). 2017;23(5, Peripheral Nerve and Motor Neuron Disorders):1360-77.
2. Carroll AS, Burns J, Nicholson G, Kiernan MC, Vucic S. Inherited Neuropathies. Semin Neurol. 2019;39(5):620-39.
3. Attarian S, Fatehi F, Rajabally YA, Pareyson D. Hereditary neuropathy with liability to pressure palsies. J Neurol. 2020;267(8):2198-206.
4. Li J, Parker B, Martyn C, Natarajan C, Guo J. The PMP22 gene and its related diseases. Mol Neurobiol. 2013;47(2):673-98.
5. Skre H. Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet. 1974;6(2):98-118.
6. Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry. 1997;62(4):310-8.
7. Braathen GJ, Sand JC, Lobato A, Hoyer H, Russell MB. Genetic epidemiology of Charcot-Marie-Tooth in the general population. Eur J Neurol. 2011;18(1):39-48.
8. Marttila M, Kytovuori L, Helisalmi S, Kallio M, Laitinen M, Hiltunen M, et al. Molecular Epidemiology of Charcot-Marie-Tooth Disease in Northern Ostrobothnia, Finland: A Population-Based Study. Neuroepidemiology. 2017;49(1-2):34-9.
9. Pisciotta C, Shy ME. Neuropathy. Handb Clin Neurol. 2018;148:653-65.
10. Foley C, Schofield I, Eglon G, Bailey G, Chinnery PF, Horvath R. Charcot-Marie-Tooth disease in Northern England. J Neurol Neurosurg Psychiatry. 2012;83(5):572-3.
11. van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies. Orphanet J Rare Dis. 2014;9:38.
12. Shy M, Lupski J, Chance P, Klein C, Dyck P. Hereditary Motor and Sensory Neuropathies: An overview of Clinical, Genetic, Electrophysiologic, and Pathologic Features. In: PJ D, PK T, editors. Peripheral Neuropathy: Philadelphia: Elsevier Saunders; 2005. p. 1623–58.
13. Meretoja P, Silander K, Kalimo H, Aula P, Meretoja A, Savontaus ML. Epidemiology of hereditary neuropathy with liability to pressure palsies (HNPP) in south western Finland. Neuromuscul Disord. 1997;7(8):529-32.
14. Rakocević-Stojanović V. Nasledne neuropatije. In: Medicinski fakultet Univerziteta u Beogradu, editor. Neuropatije Principi savremene dijagnostike i terapije. Beograd: Akademska misao; 2018. p. 209-36.
15. Klein CJ. Charcot-Marie-Tooth Disease and Other Hereditary Neuropathies. Continuum (Minneap Minn). 2020;26(5):1224-56.
16. McGrath MC. Charcot-Marie-Tooth 1A: A narrative review with clinical and anatomical perspectives. Clin Anat. 2016;29(5):547-54.
17. Birouk N, Gouider R, Le Guern E, Gugenheim M, Tardieu S, Maisonobe T, et al. Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain. 1997;120 ( Pt 5):813-23.
18. Kovach MJ, Lin JP, Boyadjiev S, Campbell K, Mazzeo L, Herman K, et al. A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness. Am J Hum Genet. 1999;64(6):1580-93.
19. Sambuughin N, de Bantel A, McWilliams S, Sivakumar K. Deafness and CMT disease associated with a novel four amino acid deletion in the PMP22 gene. Neurology. 2003;60(3):506-8.
20. Pareyson D, Scaioli V, Taroni F, Botti S, Lorenzetti D, Solari A, et al. Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion. Neurology. 1996;46(4):1133-7.
21. Hardon WJ, Van Alfen N, Zwarts MJ, Rotteveel JJ. Hereditary neuropathy with liability to pressure palsies in a toddler. Neurology. 2002;59(12):2008.
22. Paprocka J, Kajor M, Jamroz E, Jezela-Stanek A, Seeman P, Marszal E. Hereditary neuropathy with liability to pressure palsy. Folia Neuropathol. 2006;44(4):290-4.
23. Orstavik K, Skard Heier M, Young P, Stogbauer F. Brachial plexus involvement as the only expression of hereditary neuropathy with liability to pressure palsies. Muscle Nerve. 2001;24(8):1093-6.
24. Dubourg O, Mouton P, Brice A, LeGuern E, Bouche P. Guidelines for diagnosis of hereditary neuropathy with liability to pressure palsies. Neuromuscul Disord. 2000;10(3):206-8.
25. Iwasaki Y, Iguchi H, Ikeda K, Kano O. CNS involvement in hereditary neuropathy with pressure palsies (HNPP). Neurology. 2007;68(23):2046.
26. Poloni TE, Merlo IM, Alfonsi E, Marinou-Aktipi K, Botti S, Arrigo A, et al. Facial nerve is liable to pressure palsy. Neurology. 1998;51(1):320-2.
27. Verhagen WI, Gabreels-Festen AA, van Wensen PJ, Joosten EM, Vingerhoets HM, Gabreels FJ, et al. Hereditary neuropathy with liability to pressure palsies: a clinical, electroneurophysiological and morphological study. J Neurol Sci. 1993;116(2):176-84.
28. Davies DM. Recurrent peripheral nerve palsies in a family. Lancet. 1954;267(6832):266-8.
29. Winter WC, Juel VC. Hypoglossal neuropathy in hereditary neuropathy with liability to pressure palsy. Neurology. 2003;61(8):1154-5.
30. Ohkoshi N, Kohno Y, Hayashi A, Wada T, Shoji S. Acute vocal cord paralysis in hereditary neuropathy with liability to pressure palsies. Neurology. 2001;56(10):1415.
31. Lewis RA, Sumner AJ, Shy ME. Electrophysiological features of inherited demyelinating neuropathies: A reappraisal in the era of molecular diagnosis. Muscle Nerve. 2000;23(10):1472-87.
32. Pareyson D, Scaioli V, Laura M. Clinical and electrophysiological aspects of Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):3-22.
33. Behse F, Buchthal F, Carlsen F, Knappeis GG. Hereditary neuropathy with liability to pressure palsies. Electrophysiological and histopathological aspects. Brain. 1972;95(4):777-94.
34. Cruz-Martinez A, Arpa J, Palau F. Peroneal neuropathy after weight loss. J Peripher Nerv Syst. 2000;5(2):101-5.
35. Earle N, Zochodne DW. Is carpal tunnel decompression warranted for HNPP? J Peripher Nerv Syst. 2013;18(4):331-5.
36. Heng HS, Tang SS, Goyal S, Wraige EA, Lim MJ. Beneficial use of steroids in hereditary neuropathy with liability to pressure palsy. Dev Med Child Neurol. 2012;54(2):183-6.
37. Passage E, Norreel JC, Noack-Fraissignes P, Sanguedolce V, Pizant J, Thirion X, et al. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat Med. 2004;10(4):396-401.
38. Meyer zu Horste G, Prukop T, Liebetanz D, Mobius W, Nave KA, Sereda MW. Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy. Ann Neurol. 2007;61(1):61-72.
39. Attarian S, Young P, Brannagan TH, Adams D, Van Damme P, Thomas FP, 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(1):433.
40. Zhao HT, Damle S, Ikeda-Lee K, Kuntz S, Li J, Mohan A, et al. PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models. J Clin Invest. 2018;128(1):359-68.
41. Krauter D, Ewers D, Hartmann TJ, Volkmann S, Kungl T, Fledrich R, et al. Inversely proportional myelin growth due to altered <em>Pmp22</em> gene dosage identifies PI3K/Akt/mTOR signaling as a novel therapeutic target in HNPP. bioRxiv. 2021:2021.11.08.467756.