Objective: To explore the genetic spectrum of hereditary spastic paraparesis in Indian patients.

Background: HSP belongs to a heterogenous group of monogenic neurological disorders with multi-axial involvement. Its prevalence is between 2-5 per 100,000 population and is associated with length dependent degeneration of the corticospinal tracts. The inheritance pattern ranges between autosomal recessive, autosomal dominant, X-linked and mitochondrial types with 13-40% cases being sporadic. SPG4 mutations on the spastin gene is the most commonly HSP subtype worldwide. Approximately 50% cases remain undiagnosed despite genetic testing.

Method: We prospectively enrolled all suspected HSP cases (based on clinical and radiological findings) who presented to the Neurology out patient department of a tertiary care centre in India between January 2021 to December 2022. Genetic testing was carried by whole exome sequencing from the DNA extracted from the blood of these individuals.

Results: 51 suspected HSP cases underwent genetic testing during this duration and 24 were found to be positive for pathogenic mutations on HSP genes. We had a male predominance (M:F=7:1) with a median age of 21 years. The approximate symptom duration before diagnosis was 5.5 years with SPG11 mutations being the most common (n=11). These were followed by SPG7 and SPG4 (n=3 for both), 2 cases of HSP76 and one case each of SPG30, SPG31, SPG3A, SPG6 and SPG8. The differences between SPG11 mutations versus the others are highlighted in table 1. We also observed a founder mutation at SPG11 locus in our cohort confined to one ethnic population.

Conclusion: HSP is a heterogenous disease with varied clinical presentations in addition to spastic paraparesis. SPG11 mutations might be the commonest in the Indian subcontinent.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spectrum-of-hereditary-spastic-paraparesis-hsp-a-study-from-india/