Towards a patient-centred classification of genetic disease severity

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.