190P Spectrum of phenotypes in SMA patients with four SMN2 copies in France (Registre SMA France)

• Published in: Neuromuscular disorders : NMD 2024-10, Vol.43, p.104441, Article 104441.441
• Main Authors: Banda, M. Gomez Garcia De La, Gerin, L., Ropars, J., Garcia-Uzquiano, R., Saugier-Veber, P., Desguerre, I., Salort-Campana, E., Espil, C., Barnerias, C., Laugel, V., Cances, C., Audic, F., Cintas, P., Tard, C., Goff, L. Le, Dieterich, K., Drunat, S., Grimaldi, L., Quijano-Roy, S.
• Format: Article
• Language: English
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.450

The clinical presentation and prognosis of individuals harbouring four copies of SMN2 gene are not well-known and presymptomatic treatment remains controversial. The aim of this study was to describe the clinical phenotypes associated with 4 SMN2 copies in France. Collected data from all SMA patients with 0SMN1 and 4SMN2 enrolled in the national French Registry (Registre SMA France) were analyzed to better understand epidemiology, clinical presentation and course of the disease. SMN2 copy number was available in 872 patients of 1112 SMA enrolled patients. 140 patients (16.1%) carried four SMN2 copies (0 SMN1 4 SMN2). Median age at onset was 3.5 years (6 months to 20 years) and median follow-up was 32 years. 12 patients (8.6%) never walked independently (SMA type 2). 72% of the cohort was able to stand or walk with support. Independent walking was acquired in 91% (123 SMA3, 5 SMA4) and one third of them lost this ability (median 16 years). Loss of ambulation was significantly earlier in children with onset before 3 years (SMA3a). There was a significant predominance of men in the whole cohort (63%) and in sub-cohorts (SMA2-83%; SMA3-61%; adult population-68%). There was a significant lower risk for women to lose ambulation (p=0.01). 65% of patients used a wheelchair. Scoliosis surgery and ventilation was required in less than 15%. Most SMA patients with 4 SMN2 copies in the French population showed an onset during childhood and a progressive course with absence or loss of ambulation before adulthood. Presymptomatic treatment seems an acceptable option to consider, although identification of individual pejorative markers of early or severe phenotypes would allow more tailored approaches. Our results confirm the phenotypic variability reported in literature, suggesting an overall gender effect in this population.