Mortality Patterns and Phenotypic Clusters in Trisomy 13: A Population-Based Study From Japan

Trisomy 13, the third most common autosomal trisomy after trisomy 21 and trisomy 18, is associated with a significantly high infant mortality rate. However, large-scale studies examining causes of death in trisomy 13 remain scarce. Therefore, we aimed to better understand the mortality patterns. To this end, a population-based study was conducted using Japanese population-based mortality data from the Vital Statistics Database (n = 4,230,092 death records); we examined early mortality and identified phenotypic subgroups based on combinations of co-occurring causes of death. We identified 150 individuals with trisomy 13 who died between 2019 and 2021. Cardiovascular disease was significantly associated with early mortality. Using K-means clustering based on principal components of cause-of-death categories, we identified three distinct subgroups: respiratory-dominant (19%), cardiovascular-dominant (64%), and multi-organ involvement (17%). The cardiovascular-dominant cluster showed the highest rate of death before age 1 (83%; p = 0.001), while surgical intervention rates did not significantly differ across clusters. These findings highlight phenotypic heterogeneity and may support individualized care planning for trisomy 13 and provide insights that may support future care and decision-making.