Decoding the Orofacial Phenotype of Mucopolysaccharidosis: From Clinical Features to Dental Implications—A Narrative Review

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage disorders in which impaired glycosaminoglycan degradation triggers a complex cascade of cellular and tissue changes with multisystemic consequences. The craniofacial complex is frequently involved, yet oral and maxillofacial abnormalities are often described as isolated findings rather than interconnected expressions of the disease. This narrative review explores the orofacial phenotype of MPSs as the result of both developmental disturbances and progressive tissue remodeling. Current evidence on craniofacial growth, temporomandibular joint involvement, dental development, eruption disturbances, follicular changes, malocclusion, and soft-tissue abnormalities is integrated with emerging concepts of MPS pathogenesis. Particular attention is given to distinguishing developmental changes, such as enamel defects and altered tooth morphology, from progressive manifestations, including condylar resorption, skeletal remodeling, and functional limitation. Imaging findings are considered not only as diagnostic features but also as potential markers of phenotypic evolution and disease burden. Orofacial involvement may have consequences extending well beyond morphology, affecting mastication, swallowing, speech, airway function, oral hygiene, and oral-health-related quality of life. Moreover, the persistence of some craniofacial abnormalities despite disease-modifying therapies highlights possible differences in tissue-specific treatment response and reinforces the importance of long-term follow-up. By connecting pathogenesis, phenotype, imaging, and function, the craniofacial complex emerges as a clinically accessible window into the broader course of MPS. Recognizing these relationships may support earlier identification of orofacial involvement, more meaningful longitudinal monitoring, individualized dental management, and closer integration of dental professionals into multidisciplinary care.