In the HSP-MD cohort, patients with SPG49 (0.3 ± 0.4 years) and SPG20 (3.0 ± 5.5 years) genotypes had the youngest age of onset, while those with SPG7 (34.4 ± 12.7 years) and SPG8 (33.5 ± 14.2 years) were the oldest at the time of initial manifestation (Supplementary Table 1 and Supplementary Fig. 3). This evidence concerns the gene SPG7 and Menkes disease.