A rare case of hereditary spastic paraplegia with homozygous mutation in the ZFYVE26 gene.

Abstract

Hereditary spastic paraplegia (HSP) refers to a group of rare, progressive neurodegenerative disorders characterized by spasticity and weakness predominantly affecting the lower limbs, with significant clinical and genetic heterogeneity. Clinically, HSP is classified into "pure" and "complicated" forms. SPG15 (ZFYVE26) is a rare autosomal recessive subtype typically presenting in childhood with cognitive decline, followed by the development of gait disturbances and spasticity, often accompanied by thinning of the corpus callosum. Here, we report the case of a 19-year-old female patient, born to consanguineous parents, presenting with gait disturbance, lower limb spasticity, and dysarthria. Neurological examination revealed motor and mental retardation, bilateral lower limb spasticity, increased deep tendon reflexes, thinning of the corpus callosum on brain MRI, white matter hyperintensities, and the characteristic "lynx ear sign". Electromyography demonstrated marked sensorimotor demyelinating polyneuropathy in the lower limbs and evidence of anterior horn cell involvement. Genetic analysis, prompted by clinical and radiological findings, revealed a homozygous mutation in exon 19 of the ZFYVE26 gene: c.3382C>T p.Q1128*.