Oral — Health, Diseases, Therapies, and Technologies

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.

Background: Amelogenesis imperfecta (AI) has recently been realized as not only an inherited enamel anomaly, but also a genetically heterogeneous developmental disorder and a compelling model for the study of enamel biomineralization and craniofacial development. Methods: This review is a narrative synthesis of the state of the art of AI genetics, genotype–phenotype relationships, ameloblast biology, enamel biomineralization, molecular diagnosis and new approaches to regeneration by biomimetic nanomaterials, stem cell engineering, use of organoids, 3D bioprinting, and gene editing. Results: Pathogenic variants of enamel matrix proteins, proteolytic enzymes, ion transport, intracellular trafficking, and signaling between cells and the matrix provide insights into different molecular mechanisms underlying hypoplastic, hypomineralized (hypomaturation), and hypomineralized (hypocalcified) disease. The incorporation of new techniques, such as next-generation sequencing, functional genomics, multi-omics, and computational methods is changing the paradigm of AI from phenotype-based classification to one of molecularly stratified and personalized diagnosis. At the same time, emerging experimental approaches—including biomimetic mineralization, engineered ameloblast-like cells, organoid systems, and genome-editing technologies—provide promising platforms for investigating enamel regeneration, although their clinical applicability remains to be established. Conclusions: AI provides a valuable mechanistic framework for advancing research toward patient-specific, biologically informed approaches in developmental biology, precision dentistry, and regenerative craniofacial medicine; however, regenerative interventions remain investigational and require substantial preclinical validation before potential clinical translation.

Objective: The aim of this study was to determine whether smartphone- and intraoral camera-derived CIELAB parameters reproduce spectrophotometric colour variation across ICDAS defined occlusal caries severity, agree with spectrophotometric measurements, and support machine learning classification and cross-modality transfer. Methods: A total of 298 extracted posterior teeth were classified as sound (ICDAS 0), initial (ICDAS 1–2), or moderate (ICDAS 3–4) lesions. Spectrophotometric measurements were obtained from five predefined occlusal sites per tooth. Each tooth was also imaged using a smartphone and intraoral camera under standardised conditions, and five corresponding regions of interest were analysed for image-derived CIELAB values. CIELAB patterns and agreement were assessed using Linear Mixed-Effects models, Intraclass Correlation Coefficients (ICCs), and Bland–Altman analysis. Nineteen tooth-level colour and spatial variation features were evaluated using five classifiers with stratified fivefold tooth-level cross-validation and identical fold assignments across modalities. Cross-modality transfer was assessed using spectrophotometer-trained models applied to aligned image-derived features. Results: Spectrophotometry showed the most consistent severity-related decrease in L* and increases in a* and b*. Smartphone measurements broadly reproduced the L* pattern and differentiated severity through a*, whereas intraoral cameras showed limited separation for L* and b*. Agreement was device- and coordinate-dependent; the highest ICCs were observed for smartphone L* (0.785) and intraoral camera a* (0.844), while systematic bias and wide limits of agreement indicated non-interchangeability. Smartphone-derived features achieved the highest balanced accuracy (0.836–0.918), followed by the intraoral camera (0.639–0.664) and spectrophotometry (0.443–0.552). Cross-modality transfer remained partial, with prediction agreement of 54.0–74.5% (k = 0.263–0.541). Conclusions: Image-derived CIELAB features captured lesion-related colour information but were not directly interchangeable with spectrophotometry. Image derived features performed best when the model was trained and tested using data from the same measurement method. Cross-device generalisability across different camera systems remains to be established.