Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012-2022).

As part of the third French National Plan for Rare Diseases, the AnDDI-Rares network compared diagnostic practice for developmental anomalies in 34 French centres, using a randomly selected week in 2012 and one in 2022, in the context of genome sequencing (GS) rollout through the France Genomic Medicine Plan. Activity rose by 28% (430 patients in 2012, 551 in 2022) and the overall diagnostic yield increased from 16% to 27% (p < 0.001), alongside wider use of next-generation sequencing and the shift from targeted gene panels to GS. Among undiagnosed 2012 patients who pursued further investigations, next-generation sequencing provided additional diagnoses, with a GS yield of 42% in individuals with long diagnostic odysseys. Strategies remained heterogeneous across centres, with unequal access to GS, attrition and limited uptake of renewed investigations.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This is a rare snapshot of real-world French practice before and after the arrival of genome sequencing, and the 42% yield in patients with long diagnostic odysseys is a strong argument for reopening unsolved cases. Sampling one week per year limits the reach of between-centre comparisons. The main message is organisational: unequal access to GS and failure to recall patients weigh as much as the technology.

Analysis by Dr Thibaut Benquey