Clinical Phenotype of Pediatric and Adult Patients With Spinal Muscular Atrophy With Four SMN2 Copies: Are They Really All Stable?

被引：12

作者：

Ricci, Martina ^{[1
,2
]}

Cicala, Gianpaolo ^{[1
,2
]}

Capasso, Anna ^{[1
,2
]}

Coratti, Giorgia ^{[1
,2
]}

Fiori, Stefania ^{[3
]}

Cutrona, Costanza ^{[1
]}

D'Amico, Adele ^{[4
]}

Sansone, Valeria A. ^{[5
]}

Bruno, Claudio ^{[6
]}

Messina, Sonia ^{[7
]}

Mongini, Tiziana ^{[8
]}

Coccia, Michela ^{[9
]}

Siciliano, Gabriele ^{[10
]}

Pegoraro, Elena ^{[11
]}

Masson, Riccardo ^{[12
]}

Filosto, Massimiliano ^{[13
,14
]}

Comi, Giacomo P. ^{[15
,16
]}

Corti, Stefania ^{[15
,16
]}

Ronchi, Dario ^{[15
,16
]}

Maggi, Lorenzo ^{[17
]}

D'Angelo, Maria G. ^{[18
]}

Vacchiano, Veria ^{[19
]}

Ticci, Chiara ^{[20
]}

Ruggiero, Lucia ^{[21
]}

Verriello, Lorenzo ^{[22
]}

Ricci, Federica S. ^{[8
]}

Berardinelli, Angela L. ^{[23
]}

Maioli, Maria Antonietta ^{[24
]}

Garibaldi, Matteo ^{[25
]}

Nigro, Vincenzo ^{[26
,27
]}

Previtali, Stefano C. ^{[28
]}

Pera, Maria Carmela ^{[1
,2
]}

Tizzano, Eduardo ^{[29
]}

Pane, Marika ^{[1
,2
]}

Tiziano, Francesco Danilo ^{[3
]}

Mercuri, Eugenio ^{[1
,2
,30
]}

机构：

[1] Univ Cattolica Sacro Cuore, Pediat Neurol, Rome, Italy

[2] Fdn Agostino Gemelli IRCCS, Ctr Clin Nemo, Rome, Italy

[3] Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, Sect Genom Med, Rome, Italy

[4] Bambino Gesu Pediat Hosp, Dept Neurosci, Unit Neuromuscular & Neurodegenerat Disorders, IRCCS, Rome, Italy

[5] Univ Milan, ASST Niguarda Hosp, NEMO Ctr Milan, Neurorehabil Unit, Milan, Italy

[6] Univ Genoa, IRCCS Ist Giannina Gaslini, Ctr Translat & Expt Myol, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[7] Univ Messina, Dept Clin & Expt Med, Messina, Italy

[8] AOU Citta Salute & Sci Torino, Presidio Molinette & OIRM SS Malattie neuromuscola, Turin, Italy

[9] AOU Osped Riuniti Ancona, Dept Neurol Sci, Ancona, Italy

[10] AOU Pisana, Dept Clin & Expt Med, Neurol Unit, Pisa, Italy

[11] Azienda Osped Padova, Neurol Unit, Padua, Italy

[12] Fdn IRCCS Ist Neurol Carlo Besta, Dev Neurol Unit, Milan, Italy

[13] Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy

[14] NeMO Brescia Clin Ctr Neuromuscular Dis, Brescia, Italy

[15] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Neurol Unit, Milan, Italy

[16] Univ Milan, Dino Ferrari Ctr, Dept Pathophysiol & Transplantat, Milan, Italy

[17] Fdn IRCCS Ist Neurol Carlo Besta, Dev Neurol Unit, Milan, Italy

[18] Sci Inst IRCCS E Medea, NeuroMuscular Unit, Lecce, Italy

[19] IRCCS Inst Neurol Sci Bologna, UOC Clin Neurol, Bologna, Italy

[20] A Meyer Childrens Hosp, Metab Unit, Florence, Italy

[21] Federico II Univ Naples, Dept Neurosci Reprod Sci & Odontostomatol, Naples, Italy

[22] Univ Hosp Santa Maria della Misericordia, Dept Neurosci, Neurol Unit, Udine, Italy

[23] C Mondino Fdn, Pavia, Italy

[24] ASSL, Ctr Sclerosi Multipla, PO Binaghi, Cagliari, Italy

[25] Sapienza Univ Rome, St Andrea Hosp, Dept Neurosci Mental Hlth & Sensory Organs NESMOS, Rome, Italy

[26] Univ Campania Luigi Vanvitelli, Dept Precis Med, Med Genet & Cardiomyol Unit, Naples, Italy

[27] TIGEM, Pozzuoli, Italy

[28] IRCCS San Raffaele Sci Inst, Div Neurosci, Inst Expt Neurol INSPE, Milan, Italy

[29] Hosp Vall Hebron Barcelona, Dept Clin & Mol Genet, Med Genet Grp, VHIR, Barcelona, Spain

[30] Fdn Policlin Univ A Gemelli IRCCS, Dept Lab Sci & Infect Dis, Unit Med Genet, Rome, Italy

来源：

ANNALS OF NEUROLOGY | 2023年 / 94卷 / 06期

关键词：

SHAM CONTROL; COPY NUMBER; GENE; NUSINERSEN;

D O I：

10.1002/ana.26788

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. Methods: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). Results: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow-up = 36.9 +/- 19 years). Six of the 169 patients were presymptomatic, 8 were classified as type II, 145 as type III (38 type IIIA and 107 type IIIB), and 8 as type IV. The remaining 2 patients were asymptomatic adults identified because of a familial case. The cross-sectional functional data showed a reduction of scores with increasing age. Over 35% of the type III and 25% of the type IV lost ambulation (mean age = 26.8 years +/- 16.3 SD). The risk of loss of ambulation was significantly associated with SMA type (p < 0.0001), with patients with IIIB and IV less likely to lose ambulation compared to type IIIA. There was an overall gender effect with a smaller number of women and a lower risk for women to lose ambulation. This was significant in the adult (p = 0.009) but not in the pediatric cohort (p = 0.43). Interpretation: Our results expand the existing literature on natural history of 4 SMN2 copies confirming the variability of phenotypes in untreated patients, ranging from type II to type IV and an overall reduction of functional scores with increasing age.

引用

页码：1126 / 1135

页数：10

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