Revisiting Spontaneous Keloids: Aetiology, Genetics and Evidence for a Polygenic Pathogenesis

Keloids are abnormal scars resulting from dysregulated wound healing extending beyond the original injury. While typically triggered by trauma, rare cases of spontaneous keloid formation challenge this paradigm and suggest potential endogenous drivers. This study synthesises all reported cases to date and explores pathogenic mechanisms underlying their diverse etiologies. Special emphasis is placed on syndromic disorders associated with spontaneous keloids, with clinical and genetic data presented to support informed diagnostic and genetic decision-making. A representative case, in which genetic testing and bioinformatic analyses uncovered potential candidate genes consistent with a polygenic model of keloid pathogenesis, is provided to illustrate the clinical relevance and complexity of this condition. The insights discussed may reframe keloid formation as not solely a reactive complication of wound healing, but rather a primary manifestation of polygenic dysregulation within wound healing cascades.