Frequently observed polyneuropathy expands phenotypic spectrum of apparently pure autosomal dominant hereditary spastic paraplegias

Abstract

Background: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous, progressive disorders with a broad spectrum of clinical presentation. Among autosomal dominant inherited forms of HSP, the most common are SPG4, SPG3 and SPG31.

Material and methods: Our aim was the clinical characterisation of a large group of patients with SPG4, SPG3 and SPG31. Neurological assessments as well as neuroimaging, electrophysiological, neuropsychological and ophthalmological examinations were performed to characterise in detail the clinical picture in HSP patients.

Results: In our study group of 179 individuals from 60 families, three forms of AD-HSP: SPG4, SPG3 and SPG31 were diagnosed in 125, 36 and 18 patients, respectively. 48 of the probands had a positive family history of autosomal dominant hereditary disorder, while the other 12 probands represented apparently isolated cases. The pure form of HSP (pHSP) was found in a large majority (138 symptomatic patients), whereas a distinctly complex phenotype (cHSP) was found only in 32 individuals. The number of patients with cHSP became greater after including the results of electroneurography.

Conclusions: The primarily pure form of HSP is present in patients with SPG4, SPG3 and SPG31. Nevertheless, the presence of additional symptoms provides evidence that in AD-HSP not only the cortico-spinal tract is involved. The most common additional symptom is polyneuropathy. We suggest that all patients with a genetic diagnosis of SPG4 and SPG3 should have electrophysiological testing performed, and then periodically repeated, for the purpose of controlling the involvement of peripheral nerves. We found a considerable variability, including in terms of age at onset and the progression rate of disability, mainly in SPG4.

Keywords: ATL1; REEP1; SPAST; genotype-phenotype correlations; hereditary spastic paraplegia.