Genetics in hereditary spastic paraplegias: Essential but not enough

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, phenotypegenotype 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.

Automated summary

Hereditary spastic paraplegias are rare neurodegenerative diseases characterized by lower limb spasticity, with high genetic variability and clinical diversity. While genetic mutations play a significant role, genetics alone cannot fully explain the diversity of symptoms. The discovery of biomarkers may provide insights into disease progression.