Centro di riferimento per le Malattie Neurologiche, Neuromuscolari e Distrofie Miotoniche Rare (codice: 12092004)

Responsabile Clinico: Prof. Ronerto Massa

 

  

Definizione della malattia: Disturbi Miotonici 

• Miotonici Miotonia di Thomsen/Becker o Miotonia congenita
• Distrofia Miotonica di tipo 1 o di Steinert (DM1)
• Distrofia Miotonica di tipo 2 o PROMM (DM2)

Codice Esenzione: RF0040

ICD10: G71.1

ICD9: 359.2

 

 

Trasmissione: Autosomico recessiva (Becker), autosomico dominante(Thomsen, DM1, DM2)

Come si manifesta: I disturbi miotonici si caratterizzano per la presenza del fenomeno miotonico: ipereccitabilità associata a lento rilasciamento delle fibre muscolari. Nelle forme distrofiche, tale quadro si associa ad atrofia e debolezza muscolare progressiva prevalentemente distale nella DM1 e prossimale nella DM2.

Età esordio: Qualsiasi età

Decorso: Lentamente progressivo 

Cause: Mutazione gene CLCN1 (CM), espansione tripletta CTG a carico del gene DMPK (DM1), espansione della tetrapletta CCTG del gene ZNF9 (DM2/PROMM)

Terapie: Mexiletina (trattamento sintomatico della miotonia); Monitoraggio cardiologico ed eventuale impianto di PMK/defibrillatore nella DM1 e DM2.

Prevalenza: 10/100.000 (DM1), 1/100.000 (DM2/PROMM) nella provincia di Roma (Vanacore N. et al. Neuroepidemiology 2016;46:191-7

  

 

Associazioni specializzate:
Associazione Italiana Miologia (AIM) www.miologia.org  

  

 

Progetti di ricerca: 
Nazionali:

• “Efficacy of metformin on motility and strength in myotonic dystrophy type 1. a randomized, triple blind, placebo-controlled, multicenter clinical trial.” 2020-23 Finanziato da AIFA.
• “Clinical efficacy of NIV and modafinil on excessive daytime sleepiness: a multicenter, randomized, double-blind, placebo-controlled clinical trial in DM1”. 2018-19. Finanziato da Telethon.

Internazionali:

• “A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Efficacy, Safety, and Tolerability of PXT3003 in Charcot-Marie-Tooth type 1A (CMT1A)”. 2021-23. Finanziato da Pharnext.
  
• “A Prospective, Non-interventional, Long-term, Multinational Cohort Safety Study of Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (hATTR-PN). 2021-23. Finanziato da Akcea Therapeutics, Inc.
  
• “ A Randomized, Double-blind, Placebo-controlled, multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]. 2021-23. Finanziato da Lupin Europe GmbHon.

 

Pubblicazioni scientifiche: 

• Luigetti M, Guglielmino V, Antonini G, Casali C, Ceccanti M, Chiappini MG, De Giglio L, Di Lazzaro V, Di Muzio A, Goglia M, Inghilleri M, Leonardi L, Massa R, Pennisi EM, Petrucci A, Proietti E, Rispoli M, Sabatelli M and Di Girolamo M. ATTRv in Lazio-Italy: A High-Prevalence Region in a Non-Endemic Country. Genes (Basel). 2021 May 28;12(6):829.
• Botta A, Visconti VV, Fontana L, Bisceglia P, Bengala M, Massa R, Bagni I, Cardani R, Sangiuolo FC, Meola G, Antonini G, Petrucci A, Pegoraro E, D'Apice MR, Novelli G. A 14-years Italian experience in DM2 genetic testing: frequency and distribution of normal and premutated CNBP alleles. Frontiers in Genetics, 2021, in press.
• Sansone VA, Proserpio P, Mauro L, Lizio A, Frezza E, Lanza A, Rogliani P, Pezzuto G, Falcier E, Ferrari Aggradi C, Pirola A, Rao F, Roma E, Galluzzi C, Spanetta M, Cattaneo F, Rubino A, Agostoni EC, Amico F, Zanolini A, Izzi F, Greco G, Romigi A, Liguori C, Nobili L, Placidi F, Massa R. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1 (DM1). J Clin Sleep Med, 2021, in press
• Saggio, G. Manoni, A. Errico, V. Frezza, E. Mazzetta, I. Rota, R. Massa, R. Irrera, F. Objective assessment of walking impairments in myotonic dystrophy by means of a wearable technology and a novel severity index. Electronics (Switzerland)Volume 10, Issue 6, 2 March 2021, Article number 708, Pages 1-13
• Grillo P, DI Giuliano F, Massa R, Mercuri NB, Schirinzi T. Movement disorders in primary central nervous system lymphoma: two unreported cases and a review of literature. Neurol Sci. 2021 Mar;42(3):905-910.
• Frezza E, Fuccillo E, Petrucci A, Greco G, Nucera G, Bruno E, Giardina E, Tupler R, Di Mauro R, Di Girolamo S, Massa R. Cochlear Dysfunction Is a Frequent Feature of Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1). Otol Neurotol. 2021 Jan;42(1):18-23.
• Montagnese F, Rastelli E, Stahl K, Massa R, Schoser B. How to capture activities of daily living in myotonic dystrophy type 2? Neuromuscul Disord. 2020 Oct;30(10):796-806.
• Montagnese F, Rastelli E, Khizanishvili N, Massa R, Stahl K, Schoser B. Validation of Motor Outcome Measures in Myotonic Dystrophy Type 2. Front Neurol. 2020 Apr 21;11:306.
• Rossi S, Della Marca G, Ricci M, Perna A, Nicoletti TF, Brunetti V, Meleo E, Calvello M, Petrucci A, Antonini G, Bucci E, Licchelli L, Sancricca C, Massa R, Rastelli E, Botta A, Di Muzio A, Romano S, Garibaldi M, Silvestri G. Reply to the letter entitled "Predictors of respiratory impairment in patients with myotonic dystrophy type 1". J Neurol Sci. 2019 Aug 15;403:166-167.
• Rossi S, Della Marca G, Ricci M, Perna A, Nicoletti TF, Brunetti V, Meleo E, Calvello M, Petrucci A, Antonini G, Bucci E, Licchelli L, Sancricca C, Massa R, Rastelli E, Botta A, Di Muzio A, Romano S, Garibaldi M, Silvestri G. Prevalence and predictor factors of respiratory impairment in a large cohort of patients with Myotonic Dystrophy type 1 (DM1): A retrospective, cross sectional study. J Neurol Sci. 2019 Apr 15;399:118-124.
• Evoli A, Antonini G, Antozzi C, DiMuzio A, Habetswallner F, Iani C, Inghilleri M, Liguori R, Mantegazza R, Massa R, Pegoraro E, Ricciardi R, Rodolico C. Italian recommendations for the diagnosis and treatment of myasthenia gravis. Neurol Sci.2019 Jun;40(6):1111-1124.
• Massa R, Greco G, Testi M, Rastelli E, Terracciano C, Frezza E, Garibaldi M, Marfia GA, Locatelli F, Mercuri NB, Pompeo E, Antonini G, Andreani M. Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity. J Neurol. 2019 Apr;266(4):982-989. R-omigi A, Franco V, Placidi F, Liguori C, Rastelli E, Vitrani G, Centonze D, Massa R. Comparative Sleep Disturbances in Myotonic Dystrophy Types 1 and 2. Curr Neurol Neurosci Rep. 2018 Oct 31;18(12):102.
• Frezza E, Terracciano C, Giacanelli M, Rastelli E, Greco G, Massa R. Late-Onset Pompe Disease with Nemaline Bodies. Case Rep Neurol Med. 2018 Sep 27;2018:4127213.
• Cutellè C, Rastelli E, Gibellini M, Greco G, Frezza E, Botta A, Terracciano C, Massa R. Validation of the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1. Neuromuscul Disord. 2018 Nov;28(11):947-951.
• Astrea G, Romano A, Angelini C, Antozzi CG, Barresi R, Battini R, Battisti C, Bertini E, Bruno C, Cassandrini D, Fanin M, Fattori F, Fiorillo C, Guerrini R, Maggi L, Mercuri E, Morani F, Mora M, Moro F, Pezzini I, Picillo E, Pinelli M, Politano L, Rubegni A, Sanseverino W, Savarese M, Striano P, Torella A, Trevisan CP, Trovato R, Zaraieva I, Muntoni F, Nigro V, D'Amico A, Santorelli FM; Italian CMD Network. Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: an Italian cross-sectional study. Orphanet J Rare Dis. 2018 Sep 26;13(1):170.
• Spitalieri P, Talarico RV, Murdocca M, Fontana L, Marcaurelio M, Campione E, Massa R, Meola G, Serafino A, Novelli G, Sangiuolo F, Botta A. Generation and Neuronal Differentiation of hiPSCs From Patients With Myotonic Dystrophy Type 2. Front Physiol. 2018 Jul 27;9:967.
• Rastelli E, Montagnese F, Massa R, Schoser B. Towards clinical outcome measures in myotonic dystrophy type 2: a systematic review. Curr Opin Neurol. 2018 Oct;31(5):599-609.
• Ricci G, Baldanzi S, Seidita F, Proietti C, Carlini F, Peviani S, Antonini G,Vianello A, Siciliano G; Italian GSD II group. A mobile app for patients with Pompe disease and its possible clinical applications. Neuromuscul Disord. 2018 Jun;28(6):471-475.
• Terracciano C, Pachatz C, Rastelli E, Pastore FS, Melone MAB, Massa R. Neurofibromatous neuropathy: An ultrastructural study. Ultrastruct Pathol. 2018 May-Jun;42(3):312-316.
• Santoro M, Fontana L, Maiorca F, Centofanti F, Massa R, Silvestri G, Novelli G, Botta A. Expanded [CCTG]n repetitions are not associated with abnormalmethylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients.Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):917-924.
• Vizzaccaro E, Terracciano C, Rastelli E, Massa R. Aquaporin 4 expression in human skeletal muscle fiber types. Muscle Nerve. 2018 May;57(5):856-858.
• Campione E, Ventura A, Garofalo V, Torti C, Massa R, Terracciano C, Orlandi A, Bianchi L. Nodular morphea in a patient with Steinert disease. G Ital Dermatol Venereol. 2019 Apr;154(2):209-210.