Two Sibling Cases of Spastic Paraplegia-45 with a Novel Pathogenic Variant in <i>NT5C2</i> Gene: Concomitant <i>RYR1</i> Gene in One Sibling

Abstract

<b><i>Introduction:</i></b> Hereditary spastic paraplegia (<i>SPG</i>) is a genetically and clinically heterogeneous group of rare neurodegenerative disorders. SPG45 is the AR inherited type of complicated SPG, which is due to a mutation in the <i>NT5C2</i> gene. <b><i>Case Presentation:</i></b> Two sisters, aged 8 and 4, exhibited delayed motor development since early childhood. They also experienced learning difficulties, dysarthric speech, ataxia, nystagmus, strabismus, and spasticity in their extremities. Additionally, brisk deep tendon reflexes were observed in their upper and lower limbs, and they exhibited positive pathological reflexes. Whole-exome sequencing identified a previously unidentified homozygous mutation in the <i>NT5C2</i> gene, leading to the diagnosis of SPG45 in both siblings. A mutation in the <i>RYR1</i> gene associated with malignant hyperthermia was also detected in one of the siblings, necessitating ongoing monitoring. <b><i>Discussion/Conclusion:</i></b> To the best of our knowledge, we report the first case of a patient with coexistence of the <i>NT5C2</i> gene and the <i>RYR1</i> gene.