Gerin Lorène, Ropars Juliette, Garcia-Uzquiano Rocío, Gómez-García De la Banda Marta, Saugier-Veber Pascale, Desguerre Isabelle, Salort-Campana Emmanuelle, Espil Caroline, Barnerias Christine, Laugel Vincent, Cances Claude, Audic Frederique, Cintas Pascal, Le Goff Laure, Mallaret Martial, Nouguès Marie-Christine, Drunat Séverine, Tard Céline, Grimaldi Lamiae, Quijano-Roy Susana
Centre de Référence Neuromusculaire NEIDF (FILNEMUS), Service de Neuropédiatrie et Réanimation, Hôpital Raymond Poincaré (UVSQ) APHP Université Paris-Saclay, Garches, France.
Centre de Référence Neuromusculaire AOC (FILNEMUS), CHU Brest, LaTIM INSERM UMR 1101, Brest, France.
Neurol Genet. 2025 Apr 1;11(2):e200222. doi: 10.1212/NXG.0000000000200222. eCollection 2025 Apr.
Clinical phenotype and course of individuals with 4 copies of the gene are insufficiently described, and presymptomatic treatment remains controversial.
This is a cohort study that analyzed data from SMA patients with zero SMN1 and 4 SMN2 copies collected in the "Registre SMA France" to describe epidemiology, clinical presentation, and course.
A total of 140 of 1,112 patients with SMA carried 4 copies (16% of those with available copy number). The median age at onset was 3.5 years (6 months-20 years), and the median follow-up was 32 years. Twelve patients (8.6%) did not walk independently (SMA2). Of them, most were able to stand or walk with support (72%). 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 male participants in the whole cohort (63%) and in subcohorts (SMA2, 83%; SMA3, 61%; adult population, 68%). There was a significant lower risk for female participants to lose ambulation ( = 0.01). Sixty-five percent of patients used a wheelchair. Scoliosis surgery and ventilation were required in less than 15%.
Most SMA patients with 4 copies in the French population show 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 targeted approaches. Our results and literature suggest a gender effect in this population.
NCT04177134.
具有该基因4个拷贝的个体的临床表型和病程描述不足，且症状前治疗仍存在争议。
这是一项队列研究，分析了从“法国脊髓性肌萎缩症登记处”收集的零个SMN1拷贝和4个SMN2拷贝的脊髓性肌萎缩症患者的数据，以描述流行病学、临床表现和病程。
1112例脊髓性肌萎缩症患者中共有140例携带4个拷贝（占可获得拷贝数患者的16%）。发病的中位年龄为3.5岁（6个月至20岁），中位随访时间为32年。12例患者（8.6%）不能独立行走（脊髓性肌萎缩症2型）。其中，大多数人能够在支撑下站立或行走（72%）。91%（123例脊髓性肌萎缩症3型，5例脊髓性肌萎缩症4型）能够独立行走，其中三分之一失去了这种能力（中位时间16年）。3岁前发病的儿童（脊髓性肌萎缩症3a型）失去行走能力的时间明显更早。在整个队列中男性参与者占显著优势（63%），在亚组中也是如此（脊髓性肌萎缩症2型，83%；脊髓性肌萎缩症3型，61%；成年人群，68%）。女性参与者失去行走能力的风险显著较低（P = 0.01）。65%的患者使用轮椅。不到15%的患者需要进行脊柱侧弯手术和通气。
法国人群中大多数具有4个拷贝的脊髓性肌萎缩症患者在儿童期发病，病程呈进行性，在成年前出现行走能力缺失或丧失。症状前治疗似乎是一个可以考虑的可接受选择，尽管识别早期或严重表型的个体不良标记将允许采用更有针对性的方法。我们的结果和文献表明该人群存在性别效应。
NCT04177134。
