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Towards a patient-centred classification of genetic disease severity

European Journal of Human Genetics (2025)Cite this article

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Abstract

The concept of disease severity is encountered in numerous clinical situations, especially with genetic disorders. However, there is still no standardized method for defining severity. This study aimed to establish a patient-centred approach for classifying genetic disease characteristics into severity groups, with a focus on the perspectives of expectant parents. Additionally, we conducted a comparative analysis between classifications based on expectant parents’ perspectives and those based on healthcare professionals. A questionnaire was administered to 320 expectant women and their partners participating in prenatal classes. The survey gathered ratings for 28 disease characteristics, reflecting their perceived levels of severity. Using these ratings, we constructed two statistical models employing agglomerative hierarchical clustering. The disease characteristics that were most important to our cohort were a shortened lifespan, severe intellectual disability, and severe impaired mobility from childhood or adolescence onwards. Our three-tier expectant parent model revealed a strong association between the severity of disease characteristics and expectant parents’ decisions regarding pregnancy termination. On average, 89% of parents would choose to terminate a pregnancy for Tier 1 characteristics, 55% for Tier 2, and 20% for Tier 3. We found a relatively good alignment of our model with the healthcare professional-based classification, with the primary difference being that expectant parents considered a shortened lifespan more important than intellectual disability, compared to professionals. Through this study, we have gained additional insight into the core factors that expectant parents consider essential when assessing the severity of a genetic disease.

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Fig. 1: Distribution of disease characteristic severity ratings - model I.
Fig. 2: Distribution of disease characteristic severity ratings - model II.
Fig. 3: Ratings from Lazarin's study.

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Data availability

The data that support the findings of this study are available upon request.

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Funding

This study was a part of the project/program Gynecology and Reproduction: Genomics for Personalized Medicine and was financially supported by the Slovenian Research Agency (P3-0326).

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Authors and Affiliations

  1. Clinical Institute for Genomic Medicine, University Medical Centre Ljubljana, Novo mesto, Slovenia

    Mojca Cizek Sajko, Lovro Vidmar, Bernarda Prosenc & Borut Peterlin

  2. Faculty of Health Sciences, University of Novo mesto, Novo mesto, Slovenia

    Bernarda Prosenc & Borut Peterlin

  3. Clinical Department of Perinatology, Division of Gynecology and Obstetrics, University Medical Centre Ljubljana, Novo mesto, Slovenia

    Brigita Grum & Gordana Njenjic

Authors
  1. Mojca Cizek Sajko
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  2. Lovro Vidmar
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  3. Bernarda Prosenc
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  4. Brigita Grum
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  5. Gordana Njenjic
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  6. Borut Peterlin
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Contributions

BoP and LV conceived and designed the study. Data was acquired by BeP, BG and GN, and analyzed by MCS. BoP and MCS contributed to the interpretation of the results. MCS and BoP wrote the manuscript, while LV, BeP, BG, and GN revised it critically. MCS, LV, BeP, BG, GN, and BoP gave the final approval and are accountable for all aspects of the work.

Corresponding author

Correspondence to Borut Peterlin.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study protocol was reviewed and approved by Medical Ethics Committee of the Republic of Slovenia (No. 0120-464/2020/5). Written information about the study was provided to those who expressed interest in taking part. An informed consent was obtained from each participant.

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Sajko, M.C., Vidmar, L., Prosenc, B. et al. Towards a patient-centred classification of genetic disease severity. Eur J Hum Genet (2025). https://doi.org/10.1038/s41431-025-01813-0

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