Insights into the pathogenesis of macrodactyly

Mirror-image symmetry in limbs is normal in the vertebrate phenotype. Genetic and epigenetic factors regulate the differentiation, patterning, and development of the embryo and foetus. Growth after birth is influenced by hormonal and environmental factors such as nutrition. Limb size asymmetry in a child should trigger a search for associated pathology that may include neoplastic conditions, sequelae of injury, vascular, and neurogenic factors. Macrodactyly, part of the PIK3CA Related Overgrowth Spectrum, offers the physician a clinical challenge, while at the same time an opportunity to study morphology, histology, and more recently the molecular mechanisms from which the conditions arise. Collaboration between clinicians and basic scientists offers an exceptional opportunity for coordinated study and the potential for improved patient outcomes.