Clinical-Genomic Analysis of 1261 Patients with Ehlers-Danlos Syndrome Outlines an Articulo-Autonomic Gene Network (Entome).

Systematic evaluation of 80 history and 40 history findings diagnosed 1261 patients with Ehlers-Danlos syndrome (EDS) by direct or online interaction, and 60 key findings were selected for their relation to clinical mechanisms and/or management. Genomic testing results in 566 of these patients supported EDS relevance by their differences from those in 82 developmental disability patients and by their association with general rather than type-specific EDS findings. The 437 nuclear and 79 mitochondrial DNA changes included 71 impacting joint matrix (49 COL5 ), 39 bone (30 COL1/2/9/11 ), 22 vessel (12 COL3/8VWF) , 43 vessel-heart (17 FBN1 /11 TGFB / BR) , 59 muscle (28 COL6/12 ), 56 neural (16 SCN9A / 10A / 11A ), and 74 autonomic (13 POLG /25porphyria related). These genes were distributed over all chromosomes but the Y, a network analogized to an 'entome' where DNA change disrupts truncal mechanisms (skin constraint, neuromuscular support, joint vessel flexibility) and produces a mirroring cascade of articular and autonomic symptoms. The implied sequences of genes from nodal proteins to hypermobility to branching tissue laxity or dysautonomia symptoms would be ideal for large language/artificial intelligence analyses.