Infantile-onset Hereditary spastic paraplegia associated with SPAST mutations (SPG4): clinical and follow-up studies

Introduction: Hereditary spastic paraplegia (HSP) associated with SPAST mutations (SPG4) is the most frequent form of autosomal dominant HSP accounting approximately for 40% of reported cases. The phenotype associated with HSP due to mutation in the spastin gene (SPG4) tends to be pure HSP with slowly progress- ing spasticity of the legs and hyper- reflexia. Onset is mostly in the third to fifth decade but ample variability has been reported with congenital as well as late onset cases. Methods: We searched an ample series of families harboring SPAST mutation (over 100 patients) for SPG4 patients with in- fantile or congenital onset. We iden- tified 12 patients with onset rang- ing from 0 to 5 years. We reviewed past information, and assessed their clinical condition by means of clini- cal examination and SPRS scale for HSP evaluation. Results: While clini- cal characteristics of infantile-onset SPG4 is apparently similar to more common adult-onset form, the pro- gression of the disease was found to be significantly slower. Conclusions: Age of onset seems to be correlated with a significantly slower and more “benign” course of HSP as compared to classical adult-onset form. This result is clearly relevant for prognos- tic considerations as well as genetic counseling and could even reflect a different pathogenetic mechanism of SPAST mutations during fetal development and early infancy.