Clinico-Genetic Characterization of a Large Italian Cohort with Primary Spastic Paraplegia

M1002. Clinico-Genetic Characterization of a Large Italian Cohort with Primary Spastic Paraplegia Andrea Martinuzzi, Mariateresa Bassi, Grazia D’Angelo, Sara Bonato, Gabriella Paparella, Olimpia Musumeci, Mariagiovanna Rossetto, Marianna Fantin, Francesca Peruch, Alessia Arnoldi, Claudia Crimella, Erika Tenderini, Paolo Bonanni, Vanessa Casanova, Giovanni Meola, Giacomo Comi, Antonio Toscano and Nereo Bresolin; Conegliano, TV, Italy; Bosisio Parini, LC, Italy; Messina, Italy and Milano, Italy Background: Diagnostic definition of hereditary spastic paraplegias (HSPs) is complicated by the wide genetic heterogeneity. Objectives: Establish in a large cohort of Italian HSP patients the relative frequency of the various forms, provid- ing indications for an efficient diagnostic algorhythm. Methods: 478 index cases (72 familial, 98 pure, 380 complicated) HSP were clinically and molecularly assessed. Results: 80 cases were molecularly defined. SPG4 was the most frequent form (55%), followed by SPG11 (16.6%) SPG7 (9%), SPG10 (8,8% ) and 5 (5.1%). SPG3a and SPG31 were rarer (2.5%). No mutations were identified in SPG6, 8, 13, 20, 21, 35, 48. There was wide inter and intrafamilial variation. Neurophysiology showed invariably increased central conduction time at lower limbs. Axonal polyneuropathy was detected in some SPG3a, 5, 10, 11, 17 and SPG4 (15%). MRI showed abnormalities in SPG 5, 10, 11 and 15. Conclusion: Frequency of SPG forms within this cohort of Italian HSPs confirms the prevalence of SPG4, reveals the recurrence of SPG11 and 7 and the low frequency of SPG3a and 31. Once SPG4 and SPG11 are excluded, fam- ily history, neurophysiology and neuroimaging may direct the choice of genetic testing. Study supported by: Italian Ministry of Health