Orphanet Journal of Rare Diseases | A qualitative study on health-related quality of life in children and adolescents with hypohidrotic ectodermal dysplasia

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This study systematically reveals, for the first time through in-depth interviews with patients and parents, the multidimensional impact of hypohidrotic ectodermal dysplasia on the quality of life in children and adolescents, and develops a targeted patient-reported outcome measure based on real-life experiences.

 

Literature Overview

This article, 'A qualitative study on health-related quality of life in children and adolescents with hypohidrotic ectodermal dysplasia,' published in the Orphanet Journal of Rare Diseases, reviews and summarizes qualitative interview studies conducted with families affected by X-linked hypohidrotic ectodermal dysplasia (XLHED). By conducting focus groups and individual interviews, the study collected subjective experiences from 24 patients and their family members, systematically identifying six core dimensions affecting health-related quality of life (HRQoL), and developed a preliminary questionnaire (ED-QoL) to assess HRQoL in this rare disease population. The study highlights critical issues such as thermoregulatory dysfunction, appearance-related differences, and social adaptation, laying a solid foundation for the future development of disease-specific patient-reported outcome measures (PROMs). The research resulted in an age-stratified questionnaire with 83 items, available in both self-report and observer-report formats, aiming to more comprehensively capture patients' real-life experiences. Through rich quotations, the article illustrates the emotional burden, coping strategies, and unmet needs of patients and families, filling a gap in the rare disease field regarding the development of patient-centered assessment tools.

Background Knowledge

Hypohidrotic ectodermal dysplasia (HED) is a group of genetic disorders caused by abnormal development of ectodermal tissues, with X-linked hypohidrotic ectodermal dysplasia (XLHED) being the most common type. The condition is primarily caused by mutations in the EDA gene, affecting the development of sweat glands, teeth, hair, and certain glands. Patients typically present with reduced or absent sweating, missing or malformed teeth, sparse hair, and characteristic facial features. Due to impaired sweat gland function, patients have significantly compromised thermoregulation, making them prone to overheating in hot environments, which can lead to fatigue, headaches, and even seizures, potentially life-threatening in severe cases. Additionally, missing teeth affect chewing and speech development, while appearance differences may cause psychological stress and social rejection. Although clinical features are well-defined, the comprehensive impact of this condition on patients’ daily quality of life has long lacked systematic assessment. Current generic quality-of-life scales fail to capture the symptom burden specific to HED, particularly in children and adolescents, where self-reported data are especially scarce. Therefore, developing a disease-specific HRQoL assessment tool based on patients’ real experiences has become a critical need for improving clinical management and research quality. This study, grounded in FDA guidelines for PROM development, adopts a qualitative approach to systematically construct an HRQoL conceptual framework from the perspectives of patients and families, laying the foundation for the standardization and validation of future scales.

 

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Research Methods and Experiments

The study employed a qualitative research design, collecting data through semi-structured focus groups and individual interviews. Participants were recruited from the HED patient registry at the University Hospital Erlangen in Germany, including 24 patients aged 2 to 17 years and their family members, with 9 children/adolescents providing self-reports and 22 parents offering observer reports. Interviews were conducted via video conference, lasting approximately 90 minutes, and divided into two parts: the first part involved open-ended questions about the disease’s impact on quality of life; the second part involved cognitive debriefing to evaluate the understandability and relevance of a preliminary questionnaire. All interview recordings were transcribed and analyzed using MAXQDA 2022 software. A hybrid inductive-deductive approach was used to establish a classification system. The research team independently coded portions of the text to ensure reliability, reaching consensus through team discussions. Based on 562 quality-of-life-related statements, a classification system comprising six main dimensions and 45 subdimensions was developed, and a preliminary item pool was generated using card sorting.

Key Conclusions and Insights

• The study identified six core quality-of-life dimensions: physical health, emotional health, social health, autonomy, child care/schooling, and parental health—the latter being a newly identified dimension in this research
• Thermoregulatory dysfunction is the most significant factor affecting quality of life; patients often experience fatigue, weakness, headaches, nausea, or even a 'burning sensation inside' in hot environments, severely impacting daily activities and learning
• Although some children hold positive attitudes toward their condition, perceiving benefits such as 'not needing to brush teeth' or 'no body odor,' emotional distress is widespread, particularly among adolescents who exhibit irritability, low self-esteem, and anxiety about the future
• Appearance-related differences lead some children to face peer rejection and bullying, affecting social integration; however, most families report that their children receive support at home and school and feel a sense of belonging
• Restricted autonomy is evident in the inability to participate in outdoor sports or summer camps in hot environments, leading to frustration and social isolation
• Hot classrooms and physical education classes represent major challenges at school, with some students missing classes due to excessive heat, highlighting the importance of environmental adaptation
• Parents commonly experience anxiety and worry, particularly regarding infants’ risk of choking, the burden of disease management, and concerns about their children’s future social adaptation, while insufficient insurance and healthcare support further exacerbate caregiving burdens
• Based on interview data, the research team developed the 83-item ED-QoL questionnaire, available in a parent-report version for ages 2–7 and a self-report plus parent-report version for ages 8–17, laying the foundation for future validation studies

Research Significance and Outlook

This study is the first systematic qualitative exploration of quality of life in children and adolescents with HED, overcoming previous reliance on generic scales and revealing the profound impact of thermoregulatory dysfunction on psychological, social, and educational functioning. The study emphasizes that focusing solely on clinical symptoms is insufficient for a comprehensive assessment of disease burden; patient subjective experiences must be integrated to achieve truly patient-centered care.

The developed ED-QoL questionnaire provides a sensitive assessment tool for future clinical trials and long-term follow-ups, helping to detect subtle changes in response to interventions. Furthermore, the methodology can serve as a paradigm for PROM development in other rare diseases, advancing rare disease research toward greater precision and humanization. Future studies need to validate the questionnaire’s reliability and validity in larger samples and explore differences in quality of life across various genotypes and phenotypes.

 

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Conclusion

Through in-depth interviews with children affected by hypohidrotic ectodermal dysplasia and their families, this study systematically reveals the multidimensional impact of the disease on health-related quality of life. The findings show that thermoregulatory dysfunction is not only a physiological challenge but also profoundly affects emotional states, social functioning, and daily autonomy, leading to restricted learning and psychological burden. Although many families demonstrate positive adaptation, bullying, medical misunderstandings, and caregiving stress remain significant challenges. Based on real-life experiences, the study constructs an HRQoL framework encompassing six dimensions and develops a preliminary ED-QoL questionnaire, laying the foundation for the validation of standardized assessment tools. This work fills a gap in the rare disease field regarding patient-reported outcome measures and underscores the importance of incorporating patient voices into clinical decision-making. In the future, the application of this tool is expected to improve individualized management of children with HED and provide methodological insights for patient-centered research in other rare diseases. By listening to the real-life experiences of patients and families, the study advances a paradigm shift from 'treating disease' to 'improving life,' providing scientific evidence to enhance the overall well-being of the rare disease community.

 

Cosima Kügler, Stefanie Witt, Johanna Hammersen, Julia Quitmann, and Holm Schneider. Health-related quality of life of children and adolescents with the most common ectodermal dysplasia: focus group study and item development for a condition-specific patient-reported outcome measure. Orphanet Journal of Rare Diseases.