Objectives: To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA.
Methods: A retrospective analysis was performed on the medical data and survival status of 117 children with SMA.
Results: Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (P<0.05) and a significantly shorter diagnostic time window (age from disease onset to consultation) (P<0.05). Pneumonia as the initial symptom, weakness in head control, crying weakness, and eating difficulty were more commonly observed in children with type 1 SMA (P<0.05). Scoliosis and lower limb joint contracture were more common in children with type 2 SMA than in those with type 1 SMA (P<0.05). All 117 SMA children (100%) had homozygous deletion of the SMN1 gene, and the homozygous deletion of exon 7 was the most common type (68.4%, 80/117). The 6-year survival rate of children with type 1 SMA was only 10%±5%, which was significantly lower than that of children with type 2 or 3 SMA (P<0.05). Age of onset ≤3 months, pneumonia as the initial symptom and weakness in head control were the risk factors for death in children with type 1 SMA (P<0.05). The children with type 2 SMA had non-linear regression of motor ability.
Conclusions: There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.
目的: 对重庆及周边地区脊髓性肌萎缩症（spinal muscular atrophy，SMA）的自然病史进行分析，为开展SMA的综合管理、基因修饰治疗提供临床依据。方法: 回顾性分析117例SMA患儿的临床资料及生存现状。结果: 117例患儿中，1型SMA 62例（53.0%）、2型45例（38.5%）、3型10例（8.5%），中位起病年龄分别为2、10、15月龄。1型SMA起病、就诊、确诊时间均早于2、3型SMA（P<0.05），1型SMA就诊时间窗（起病年龄至就诊年龄）短于2、3型SMA（P<0.05）。肺炎为首发症状、抬头无力、哭声无力、进食费力多见于1型SMA（P<0.05），2型SMA脊柱侧弯和下肢关节挛缩发生率高于1型（P<0.05）。117例（100%）SMA患儿均为SMN1基因纯合缺失，其中以7号外显子纯合缺失最常见（68.4%，80/117）。1型SMA的6年生存率仅为10%±5%，低于2、3型SMA（P<0.05）。起病年龄≤3月龄、肺炎为首发症状、抬头无力为1型SMA死亡的危险因素（P<0.05）。2型SMA运动能力可呈非线性倒退。结论: 各型SMA患儿临床表现、生存率均存在异质性，1型SMA生存率低，2型SMA运动能力可呈非线性倒退，临床上应早期识别及管理SMA。.
Keywords: Child; Natural history; SMN1 gene; Spinal muscular atrophy; Survival analysis.