Clinical, Genetic, and Pathological Studies in Two Brothers with Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures: A Case Report

Abstract

Introduction: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive disorder caused by biallelic pathogenic variants in the ADPRS gene. Since its first description in 2018, less than fifty cases have been reported worldwide, but thus far, without histopathology of the nervous system. Case Presentation: We summarize the clinical, paraclinical, and genetic characteristics of the disease in the proband, and the pathological workup in his older brother who passed away more than a decade ago. The characteristics of CONDSIAS in the two brothers overlapped with those of Friedreich ataxia. A final clarification of the diagnosis was made possible by whole exome sequencing (WES) that identified the homozygous pathogenic variants in the ADPRS gene. Conclusion: CONDSIAS is a rare disorder with highly variable presentation. Based on solely clinical and even pathological workup, establishing a definite diagnosis may be challenging. In the two brothers, we observed clinical and histopathological features of the disease suggesting, though not completely fulfilling, the diagnosis of Friedreich’s ataxia. WES allowed us to rapidly identify the underlying genetic abnormality and to make a shortcut to the right diagnosis amongst recessive ataxias. As of today, no specific treatment for CONDSIAS is available. Repurposing of certain approved modalities that also target the affected pathway in CONDSIAS recently arose, though as yet without proven success. Knowing the biological relevance of the affected gene product offers potential targets for the development of disease-modifying drugs for this highly disabling disease in the near future.

Keywords

• childhood-onset neurodegeneration with variable ataxia and seizures
• adprs gene
• whole exome sequencing
• histopathology
• case report