The impact of vanishing white matter on unaffected family members

• Published in: Orphanet Journal of Rare Diseases
• Main Authors: Romy J. van Voorst, Daphne H. Schoenmakers, Irene van Beelen, Francesco Gavazzi, Alexandra Chapleau, Adeline Vanderver, Geneviève Bernard, Ingeborg Krägeloh-Mann, Marjo S. van der Knaap
• Format: Article
• Language: English
• Published: BMC 2025-08-01
• Subjects: Leukodystrophy; Vanishing white matter; VWM; Ultra-rare diseases; Impact of disease; Quality of life
• Online Access: https://doi.org/10.1186/s13023-025-03987-8

Abstract Background Vanishing White matter (VWM) is one of the more prevalent leukodystrophies, caused by biallelic pathogenic variants in any of the EIF2B1–5 genes. It is characterized by chronic progressive neurological deterioration and additional stress-provoked episodes of rapid decline, leading to severe neurological impairment and early death. The impact of VWM on unaffected family members has not been investigated. Methods This international cross-sectional study enrolled parents, partners, and unaffected siblings. We used online administration of (1) health-related quality of life questionnaires (quantitative, comprising the EuroQol–5-Dimensions [EQ5-D]–5-Levels questionnaire [EQ-5D-5L], EuroQol–5-Dimensions–Youth–3-Levels questionnaire [EQ-5D-Y-3L], Pediatric Quality of Life Family Impact Module [PedsQL™-FIM], PedsQL™ Child–Adult Self Report [PedsQL™-SC]); (2) VWM-specific customized questionnaires (quantitative, comprising the impact of VWM inventory questionnaires for parents, partners and siblings); and (3) in-depth semi-structured interview (qualitative). Results A total of 100 family members were included: 52 mothers, 29 fathers, 13 unaffected siblings, and 6 partners. Mothers and partners scored significantly poorer on the EQ5D-5L than the reference norms. Fathers and mothers scored significantly poorer on the PedsQL™-FIM than the reference norms. Siblings scored similar to the reference norms on the EQ5D-5L and all domains of the PedsQL™-SC, with the lowest score on the emotional domain. Qualitative interviews revealed three main drivers of the impact of VWM: (1) lack of knowledge and empathy of healthcare professionals, (2) unpredictable disease course, and (3) caregiver responsibilities. Mothers reported substantial impacts on their emotional well-being and dissatisfaction with their professional development. Fathers commonly reported financial concerns and heightened family responsibility. Partners mentioned emotional exhaustion and difficulty in managing family responsibilities. Siblings frequently reported internal struggles, finding it challenging to express their feelings. Conclusions Mothers and partners indicate a significant and consistent reduction in their quality of life on standardized questionnaires. Qualitative interviews revealed in-depth details of VWM’s impact on all family members. Improved healthcare communication, symptom management resources, and support networks are essential for alleviating VWM’s impact on families. This study emphasizes the importance of tailored approaches to supporting family members of VWM patients and enhancing their quality of life.