Hereditary spastic paraplegias consist of a group of rare neurodegenerative diseases characterized by lower limb spasticity. These inherited Mendelian disorders show high genetic variability associated with wide clinical diversity. Pathophysiological investigations have suggested that mutations in genes affecting the same cellular pathway generally lead to similar clinical symptoms, highlighting the importance of genetic mutation in these diseases. However, phenotype-genotype correlations have failed to explain the observed large inter-individual variability linked to mutations in a single gene, suggesting that genetics alone is not sufficient to explain symptom diversity. The identification of biomarkers, such as neurofilament light chain, could fill the gap and predict disease evolution.

遗传性痉挛性截瘫由一组以下肢痉挛为特征的罕见神经退行性疾病组成。这些遗传的孟德尔疾病表现出与广泛的临床多样性相关的高遗传变异性。病理生理学研究表明，影响同一细胞通路的基因突变通常会导致相似的临床症状，突出了基因突变在这些疾病中的重要性。然而，表型-基因型相关性未能解释观察到的与单个基因突变相关的巨大个体间变异性，这表明仅靠遗传学不足以解释症状多样性。生物标志物的鉴定，如神经丝轻链，可以填补空白并预测疾病的演变。