Practical DMD Course 04. Atypical Phenotypes in Dystrophinopathies

This course addresses the atypical phenotypes associated with dystrophinopathies, providing an updated overview of the wide clinical heterogeneity resulting from alterations in the DMD gene. Beyond the classic muscular involvement, it reviews the various neurological, cognitive, cardiac, ophthalmological, and systemic manifestations that may occur in patients with Duchenne muscular dystrophy (DMD), as well as in female carriers. Throughout the course, the genotype–phenotype relationship is analyzed, including the impact of different genetic variants and dystrophin isoforms on disease clinical expression. Special attention is given to brain and retinal dystrophin isoforms to better understand their association with cognitive impairment, behavioral disturbances, epilepsy, and visual involvement. The course also reviews less recognized presentations such as chronic pain, isolated X-linked cardiomyopathy, symptoms in female carriers, and contiguous gene syndromes associated with metabolic and neurodevelopmental disorders. Overall, the content provides tools to broaden clinical suspicion and improve recognition of non-classical manifestations in dystrophinopathies.