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Wolf-Hirschhorn Syndrome (WHS) was the first human chromosomal deletion identified as a variable 4p chromosomal deletion syndrome. The phenotype can vary based on the size and placement of the deletion. Its core characteristics include mental retardation, craniofacial dysmorphology, epilepsy, and growth delay; however, there can be many other defects based on the specific gene deletions. Management of this syndrome is multifaceted, and it often involves multiple specialties and lifelong care. Thus, implications for advanced practice nurses includes accurate diagnosis and treatment of defects and comorbidities involving different body systems, collaboration with different medical teams, and early intervention.