Infantile-Onset Ascending Hereditary Spastic Paraplegia due to a Homozygous ALS2 Exons 24-25 Deletion: Expanding the Genotypic Spectrum

ABSTRACT

We describe a novel homozygous intragenic deletion in the ALS2 gene in an 8-year-old boy with Infantile-onset Ascending Hereditary Spastic Paraplegia (IAHSP) and oculomotor apraxia, thereby contributing to the expanding genetic landscape of ALS2-related disorders. Comprehensive neurological evaluation, chromosomal microarray analysis (CMA), and trio-based whole exome sequencing (WES) were performed. CMA revealed a run of homozygosity (ROH) at 2q33.1. WES identified a homozygous deletion encompassing exons 24-25 of ALS2, inherited from heterozygous parents. This clinical phenotype was consistent with the IAHSP spectrum, and no previous cases due to intragenic deletion have been reported. Our findings further expand the mutational spectrum of ALS2-related disorders and underscore the relevance of combining CMA and WES in the diagnostic workup of early-onset motor disorders, particularly in consanguineous families and unresolved cases. Greater awareness of rare intragenic deletions may improve early recognition and facilitate accurate genetic counseling in pediatric neurogenetics.