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Open Access 01-12-2022 | Spastic Paraplegia | Research

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations

Authors: Jiannan Chen, Zhe Zhao, Hongrui Shen, Qi Bing, Nan Li, Xuan Guo, Jing Hu

Published in: BMC Neurology | Issue 1/2022

Abstract

Background

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis.

Methods

Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented.

Results

A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe’s disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained.

Conclusions

HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.

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Title: Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations
Authors: Jiannan Chen
Zhe Zhao
Hongrui Shen
Qi Bing
Nan Li
Xuan Guo
Jing Hu
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Spastic Paraplegia
Cranial MRI
Leukodystrophy
Published in: BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-022-02708-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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