Assessment of SMN2 copy number in patients with spinal muscular atrophy (SMA) is essential to establish careful genotype-phenotype correlations and predict disease evolution. This issue is becoming crucial in the present scenario of therapeutic advances with the perspective of SMA neonatal screening and early diagnosis to initiate treatment, as this value is critical to stratify patients for clinical trials and to define those eligible to receive medication. Several technical pitfalls and interindividual variations may account for reported discrepancies in the estimation of SMN2 copy number and establishment of phenotype-genotype correlations.

We propose a management guide based on a sequence of specified actions once SMN2 copy number is determined for a given patient. Regardless of the method used to estimate the number of SMN2 copies, our approach focuses on the manifestations of the patient to recommend how to proceed in each case.

We defined situations according to SMN2 copy number in a presymptomatic scenario of screening, in which we predict the possible evolution, and when a symptomatic patient is genetically confirmed. Unexpected discordant cases include patients having a single SMN2 copy but noncongenital disease forms, 2 SMN2 copies compatible with type II or III SMA, and 3 or 4 copies of the gene showing more severe disease than expected.

Our proposed guideline would help to systematically identify discordant SMA cases that warrant further genetic investigation. The SMN2 gene, as the main modifier of SMA phenotype, deserves a more in-depth study to provide more accurate genotype-phenotype correlations.

评估脊髓性肌萎缩症 (SMA) 患者的SMN2拷贝数对于建立仔细的基因型-表型相关性和预测疾病演变至关重要。从 SMA 新生儿筛查和早期诊断开始治疗的角度来看，在目前治疗进展的情况下，这个问题变得至关重要，因为这个值对于临床试验的患者分层和确定有资格接受药物治疗的患者至关重要。一些技术缺陷和个体差异可能导致在估计SMN2拷贝数和建立表型-基因型相关性方面报告的差异。

一旦确定给定患者的SMN2拷贝数，我们就会根据一系列指定操作提出管理指南。无论使用何种方法来估计SMN2拷贝的数量，我们的方法都侧重于患者的表现，以建议在每种情况下如何进行。

我们在症状前筛查场景中根据SMN2拷贝数定义了情况，我们预测了可能的演变，以及何时有症状的患者被基因证实。意外不一致的病例包括具有单个SMN2拷贝但非先天性疾病形式的患者，2 个SMN2拷贝与 II 或 III 型 SMA 相容，以及 3 或 4 个基因拷贝显示出比预期更严重的疾病。

我们提出的指南将有助于系统地识别需要进一步基因调查的不一致 SMA 病例。SMN2基因作为 SMA 表型的主要修饰因子，值得进行更深入的研究，以提供更准确的基因型-表型相关性。