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. 2023 Dec;94(6):1126-1135.
doi: 10.1002/ana.26788. Epub 2023 Sep 22.

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

Martina Ricci #  1   2 , Gianpaolo Cicala #  1   2 , Anna Capasso #  1   2 , Giorgia Coratti  1   2 , Stefania Fiori  3 , Costanza Cutrona  1 , Adele D'Amico  4 , Valeria A Sansone  5 , Claudio Bruno  6 , Sonia Messina  7 , Tiziana Mongini  8 , Michela Coccia  9 , Gabriele Siciliano  10 , Elena Pegoraro  11 , Riccardo Masson  12 , Massimiliano Filosto  13 , Giacomo P Comi  14   15 , Stefania Corti  14   15 , Dario Ronchi  14   15 , Lorenzo Maggi  16 , Maria G D'Angelo  17 , Veria Vacchiano  18 , Chiara Ticci  19 , Lucia Ruggiero  20 , Lorenzo Verriello  21 , Federica S Ricci  8 , Angela L Berardinelli  22 , Maria Antonietta Maioli  23 , Matteo Garibaldi  24 , Vincenzo Nigro  25   26 , Stefano C Previtali  27 , Maria Carmela Pera  1   2 , Eduardo Tizzano  28 , Marika Pane  1   2 , Francesco Danilo Tiziano  3   29 , Eugenio Mercuri  1   2 ; ITASMAC Working Group
Collaborators, Affiliations
Free article

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

Martina Ricci et al. Ann Neurol. 2023 Dec.
Free article

Abstract

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. ANN NEUROL 2023;94:1126-1135.

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References

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