The Impact of RNA Polymerase III–Related Leukodystrophy on Nonaffected Family Members: A Qualitative Study

Adam Le, Kelly Ann Thibault, Pouneh Amir Yazdani, Alexandra Chapleau, Romy J. van Voorst, Enrico Bertini, Francesco Nicita, Daniela Pohl, Sunita Venkateswaran, Stephanie Keller, Deborah Renaud, Dolores Gonzalez Moron, Marcelo Kauffman, Danilo De Assis Pereira, Adeline Vanderver, Marjo S. van der Knaap, Maxime Morsa, Geneviève Bernard*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: RNA polymerase III–related hypomyelinating leukodystrophy (POLR3-HLD) is a rare, neurodegenerative, brain white matter disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Due to the complex and progressive nature of this disorder, parents and siblings of patients face many potential challenges and stressors. We, therefore, sought to explore parents' and siblings’ experiences to understand their specific needs and identify modifiable factors to limit familial burden and improve their quality of life. 

Methods: We conducted semistructured interviews with parents and siblings of patients with POLR3-HLD. Interview questions focused on the financial, emotional, and psychosocial impacts on parents, as well as siblings’ relationship with their affected sibling and the psychosocial impacts they may have experienced. All interviews were recorded, transcribed, and analyzed using reflexive thematic analysis. Through the coding process, themes surrounding the impact on and experiences of parents and siblings were developed. 

Results: Nineteen semistructured interviews with 24 parents and nine interviews with 9 siblings were completed between March and October 2023 and February and May 2024, respectively. Four themes from parent interviews included extensive caregiver burden, emotional and psychosocial challenges, the importance of parental self-health, and comfort in the leukodystrophy community. Three themes from sibling interviews included the spectrum of emotional impacts, limited knowledge about POLR3-HLD, and adapting to their sibling's needs. 

Conclusions: This study provides a comprehensive understanding of the family experience, identifying the common challenges and specific needs of parents and siblings, highlighting areas of improvement in the global care offered to this vulnerable patient population.

Original languageEnglish
JournalPediatric Neurology
DOIs
Publication statusE-pub ahead of print - 16 Dec 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s)

Keywords

  • Burden of disease
  • Impact on siblings
  • Parents and caregivers
  • POLR3-related Leukodystrophy
  • Rare disease
  • Thematic analysis

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