Objective: To characterize the demographic, clinical and genetic features of HSP and to define the phenotypic spectrum and genotype-specific differences.

Background: Hereditary spastic paraplegia (HSP) is a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders in which the main neurological symptoms and signs are lowerlimb spasticity and weakness. According to the clinical phenotype, the HSP are classified in pure or complex forms depending on the presence of other neurological features in addition to spastic paraparesis. The estimated prevalence of HSP in Portugal is 4.1 per 100 000 inhabitants, being spastic paraplegia (SPG) types 4, 3 and 11 the most prevalent.

Methods: We present a cross-sectional study of the clinical and genetic characteristics of a cohort of patients with HSP followed at a tertiary centre in Portugal. Multiple sources of information were used (review of clinical files and active collaboration of neurologists and geneticists). Using the available protocols, including single gene and targeted next generation sequencing (NGS).

Results: A total of 43 patients were identified with HSP, and 48.84% had a confirmed genetic diagnosis. We observed a male predominance (58,14%). The mean age of disease onset was 27.25 years. The family history was suggestive of dominant inheritance in approximately half of the patients, most of them presenting a pure phenotype. We identified several forms of HSP, including thirteen patients with SPG4, four with SPG11and one with SPG3A. The NGS was been performed in patients with no molecular diagnosis and we found one patient with SPG5, one with SPG7 and one with SPG76. Additional clinical features were noted, including ataxia for SPG5 and dysarthria and pes cavus for SPG7.

Conclusions: The developmentof genetic techniques brought new possibilities for precise diagnosis and targeted NGS may be a useful method to screen for mutations in multiple genes associated with HSP.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-heterogeneity-in-portuguese-patients-with-hereditary-spastic-paraplegia/