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The recognition and documentation of novel clinical syndromes and very rare diseases remain critical to the advancement of medical knowledge, precision diagnosis, and ultimately, patient care. Over the last two decades, the author has contributed extensively to the field of rare and ultra-rare diseases through meticulous clinical observation, investigation, and publication of a wide array of new clinical entities, syndromic patterns, and disease associations, many of which had not been previously described in the medical literature. This book includes a comprehensive review which presents a synthesized account of these contributions, based on more than 40 original reports of new syndromes and disorders and over 30 first or ultra-rare case reports, covering both genetic and non-genetic etiologies. The review offers both an academic and reflective overview of the clinical journeys that led to the recognition of these entities and provides insights into the diagnostic strategies, imaging techniques, and clinical reasoning processes that enabled the identification of patterns amidst highly heterogeneous presentations.