Hereditary Spastic Paraplegia With Thin Corpus Callosum due to Compound Heterozygous Novel Mutation in SPG11 Gene: A Case Report
Year: 2025
Type: article
Study design: Case Report
Abstract: ABSTRACT Hereditary spastic paraplegia ( HSP ) encompasses a group of genetically heterogeneous neurodegenerative disorders characterized by progressive lower limb spasticity; SPG11 is a frequent autosomal recessive (AR) subtype typically presenting in adolescence with cognitive decline, thinning of the corpus callosum, and the characteristic “ears of the lynx” Magnetic resonance imaging ( MRI) sign. We report a 19‐year‐old South Asian man, born of a second‐degree consanguineous marriage, who developed insidious gait difficulty and scholastic decline over 4 years. Neurological examination revealed pyramidal weakness confined to the lower limbs with increased tone, brisk deep tendon reflexes, ankle clonus, and a spastic scissoring gait; bedsides, cognitive testing showed mild impairment ( MMSE 23) with features of executive dysfunction. His younger brother reported similar symptoms. Brain MRI demonstrated marked thinning of the corpus callosum and T2 ‐ FLAIR hyperintensity in the forceps minor consistent with the “ears of the lynx” sign. Whole exome sequencing identified compound heterozygous frameshift deletions in SPG11 : a previously reported two‐base pair deletion in exon 4 (p. Met245ValfsTer2 ) and a novel single‐base pair deletion in exon 39 (p. Val2344PhefsTer12 ), confirming the diagnosis of AR SPG11 ‐related HSP . The patient was diagnosed with symptomatic therapies including baclofen and tolperisone, physiotherapy, and ambulatory aids, with plans for regular follow‐up and genetic counseling. This case underscores the diagnostic utility of integrating clinical phenotype, characteristic neuroimaging, and genetic testing, and the identification of a novel exon 39 frameshift expands the mutational spectrum of SPG11 and highlights the importance of genetic screening in consanguineous families. Further research is needed to delineate genotype–phenotype correlations and potential therapeutic avenues and interventions.
DOI: 10.1111/ncn3.70058
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4415847699