Objective: To report the first genetically confirmed case of SPG11-associated hereditary spastic paraplegia (HSP) in the Philippines, featuring a previously undocumented splice-site mutation and comprehensive phenotypic characterization

Background: Hereditary spastic paraplegias are clinically and genetically heterogeneous disorders marked by progressive spasticity and weakness, often complicated by cognitive impairment and distinctive neuroimaging features. SPG11 is the most common autosomal recessive HSP globally but remains underdiagnosed in resource-limited populations.

Method: A 26-year-old female, with a decade-long history of progressive lower limb spasticity and cognitive decline, underwent thorough clinical, neurologic, and imaging assessments. The whole-exome sequencing identified two pathogenic SPG11 variants, including the novel c.3039-1G>A canonical splice-site mutation.

Results: The patient exhibited classic SPG11-HSP features: progressive spastic paraplegia, cognitive impairment, and radiologic signs including corpus callosum thinning and “ears-of-the-lynx.” Genetic analysis confirmed compound heterozygosity for two loss-of-function SPG11 variants, one of which is previously unreported. Symptomatic management with oral baclofen improved spasticity. Genetic counseling and multidisciplinary care were provided.

Conclusion: This case highlights the expanding mutational spectrum of SPG11 and reinforces diagnostic value of genomic testing. Early recognition, neuroimaging evaluation, and multidisciplinary management are essential to optimize outcomes. Further research is needed to address genotype-phenotype correlations and develop targeted therapies for HSP.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-spg11-splice-site-mutation-in-hereditary-spastic-paraplegia-clinical-radiologic-and-genetic-insights-from-the-first-philippine-case/