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Treatment of acute cases of amelogenesis imperfecta (AI) is challenging in children due to the absence of a consensus statement on therapeutic recommendations. This article presents the effectiveness of an interdisciplinary approach--including orthodontics, orthognathic surgery, and prosthodontics using digital technology--in a child with AI and skeletal deformities. The early management over a 6-year period had a very positive impact on the quality of life related to oral health. The full-mouth rehabilitation in adulthood with all-ceramic crowns showed a fully satisfactory result after 60 months of follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To examine the long-term performance of bonded all-ceramic restorations, specifically veneers, in patients with amelogenesis imperfecta (AI). There are few studies of long-term outcomes using a minimally invasive procedure in these patients. This aspect is essential when treating young patients. All-ceramic restorations, especially veneers, offer a more tissue-preserving treatment but rely on successful bonding. However, due to the defect enamel in AI patients, the bond strength is lower. Materials and Methods: A retrospective evaluation of 40 subjects with AI (26 women, 14 men) was provided with a total of 360 bonded restorations (282 veneers, 78 crowns). The restorations were evaluated according to complications, survival, and success rate. Results: The patients were observed up to 25.3 years (mean 15.4 ± 4.3 years). The mean age when receiving the restorations was 18.5 ± 4.2 years. In total, 59 (16.4%) restorations with prosthetic complications were made, 29 of which (8.1%) were remade (6 due to esthetic reasons, all in one patient) and 30 (8.3%) were recemented (60% caused by trauma). We found 11 teeth with caries and 3 with endodontic complications. The overall survival rate was 91.9%, and the overall success rate was 83.6%. Conclusions: Bonded all-ceramic restorations with no active retention in AI patients have excellent performance. The most common complications were debonding and fractures. The treatment should be based on individual indications and be preceded by a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

The article describes interdisciplinary dentistry (ID) and how it can be applied to better care for pediatric patients. Topics discussed include the interdisciplinary dental treatment process, ID treatment plan, and University of Washington interdisciplinary dentistry example interdisciplinary problem list template.

Background: Amelogenesis imperfecta (AI) is a group of genetic disorders characterized by tooth discoloration and enamel defects. Patients with AI always exhibit generalized attrition and defective tooth structure, leading to the loss of occlusal vertical dimension (OVD). Appropriate rehabilitation is challenging and essential to improve patients' aesthetics and function. Case presentation: This case report presents a comprehensive management of a 30-year-old woman with hypoplastic AI. A 52-month follow-up revealed satisfactory full-mouth rehabilitation performances of lithium disilicate ceramic crowns after clinical crown lengthening, with increased vertical dimension. Conclusions: Patients with severe hypoplastic AI require proper full-mouth rehabilitation. Using full-crown lithium disilicate restorations to increase the OVD by 2‒4 mm is a safe and predictable recommendation for such cases. In addition, patients with AI require complex and comprehensive management. The long-term effects of full-mouth rehabilitation with lithium disilicate ceramic crowns still necessitate further follow-ups. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is a genetic disease characterized by poor formation of tooth enamel. AI occurs due to mutations, especially in AMEL, ENAM, KLK4, MMP20, and FAM83H, associated with changes in matrix proteins, matrix proteases, cell-matrix adhesion proteins, and transport proteins of enamel. Due to the wide variety of phenotypes, the diagnosis of AI is complex, requiring a genetic test to characterize it better. Thus, there is a demand for developing low-cost, noninvasive, and accurate platforms for AI diagnostics. This case-control pilot study aimed to test salivary vibrational modes obtained in attenuated total reflection fourier-transformed infrared (ATR-FTIR) together with machine learning algorithms: linear discriminant analysis (LDA), random forest, and support vector machine (SVM) could be used to discriminate AI from control subjects due to changes in salivary components. The best-performing SVM algorithm discriminates AI better than matched-control subjects with a sensitivity of 100%, specificity of 79%, and accuracy of 88%. The five main vibrational modes with higher feature importance in the Shapley Additive Explanations (SHAP) were 1010 cm−1, 1013 cm−1, 1002 cm−1, 1004 cm−1, and 1011 cm−1 in these best-performing SVM algorithms, suggesting these vibrational modes as a pre-validated salivary infrared spectral area as a potential biomarker for AI screening. In summary, ATR-FTIR spectroscopy and machine learning algorithms can be used on saliva samples to discriminate AI and are further explored as a screening tool. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous features of enamel renal syndrome (ERS) make diagnosis and treatment challenging. The main symptoms are disturbed amelogenesis and nephrocalcinosis. Bi-allelic likely pathogenic (LP) or pathogenic (P) variants in FAM20A have been associated with the syndrome since 2012. Affected patients often receive extensive dental treatment because of deviant orofacial morphology. However, knowledge about long-term prognosis and treatment guidelines are still lacking. The complex nature of ERS might endanger both dental and general health. The purpose of this article is to highlight the risks of overlooking the symptoms of the syndrome, and to discuss management strategies, surveillance and prognosis. Case presentation: We report the management of a case with suspected ERS after initial dental treatment elsewhere with no adjustment for the syndrome. Dental treatment was revised and followed for 8 years. Complementary medical examinations were conducted, and ERS was genetically confirmed, revealing homozygosity for a LP c.755_757del, p.(Phe252del) variant in FAM20A. The nephrological investigation revealed medullary calcium deposits, normal renal function and hypophosphatemia. Urine analysis revealed hypocitraturia and hypocalciuria. Accordingly, the patient now medicates with potassium citrate to decrease the risk of progressive renal stone formation. Conclusion: We herein describe a patient with confirmed ERS with an 8-year follow-up. Diagnostic delay until adulthood led to complicated dental treatment. The results of nephrological investigations are presented. The importance of dental and medical multidisciplinary management in syndromic disorders affecting the formation of the enamel is also exemplified. The dental prognosis after rehabilitation is likely affected by anatomical variations and patient cooperation. The prognosis for renal function seems to be good. However, lifelong surveillance of renal function is recommended. Registration: The ethics committee in Uppsala, Sweden, determined that ethical approval was not necessary in this case (2019-04835). Informed consent was obtained from the participant in writing and is documented in the medical records.

Abstract Background Amelogenesis imperfecta (AI) is a group of genetic disorders characterized by tooth discoloration and enamel defects. Patients with AI always exhibit generalized attrition and defective tooth structure, leading to the loss of occlusal vertical dimension (OVD). Appropriate rehabilitation is challenging and essential to improve patients’ aesthetics and function. Case presentation This case report presents a comprehensive management of a 30-year-old woman with hypoplastic AI. A 52-month follow-up revealed satisfactory full-mouth rehabilitation performances of lithium disilicate ceramic crowns after clinical crown lengthening, with increased vertical dimension. Conclusions Patients with severe hypoplastic AI require proper full-mouth rehabilitation. Using full-crown lithium disilicate restorations to increase the OVD by 2‒4 mm is a safe and predictable recommendation for such cases. In addition, patients with AI require complex and comprehensive management. The long-term effects of full-mouth rehabilitation with lithium disilicate ceramic crowns still necessitate further follow-ups.

Enamel hypoplasia is a disease that results in enamel formation and mineralization abnormalities due to the effects of hereditary or environmental variables during tooth development. Affected teeth may appear to have an aberrant color and structural flaws. Patients often display clinical signs such as tooth defects, tooth sensitivity, and tooth discoloration. The disease can cause patients to feel physically and mentally uncomfortable and negatively impact their ability to chew, swallow, speak, and smile. In this review, the pathophysiology of enamel hypoplasia, which is caused by anomalies in gene regulation and changes in environmental variables, is summarized, along with a list of clinical diagnostic indicators based on the most commonly used disease classifications. The main points are as follows: ① enamel hypoplasia changes only the color and transparency of the affected teeth; ② lesions often occur symmetrically in groups; ③ the age at which systemic diseases or nutritional disorders occur during tooth development can be predicted based on the patient's impaired teeth; and ④ banded or pitted brown depression on the enamel surface can easily be confused with dental fluorosis. It also elaborates on the comprehensive application of tooth bleaching, desensitization, direct or indirect restoration and other treatment modalities according to unique chief complaints by different patients and suggests the use of multidisciplinary cooperative sequential treatment for critical infants and young children. The goal of this review is to provide professionals with the most recent information and advice about enamel hypoplasis. Current literature on this condition is primarily case reports. To further standardize the diagnostic and management approaches for this disease, additional high-quality clinical research and systematic reviews are required.

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Ameloblastin (Ambn) is multifunctional in its facilitation of enamel formation. • Human amelogenesis imperfecta cases and animal models emphasize importance of Ambn. • Its functions include ameloblast cell signaling, polarization, and matrix adhesion. • A conserved amphipathic helix motif mediates direct Ambn-cell membrane interaction. • The motif is part of a multitargeting domain mediating multiple Ambn interactions. • These various interactions could enable Ambn's cell polarization and adhesion roles. Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro , and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Amelogenesis imperfecta (AI) is a rare developmental anomaly characterized by poorly developed or absent tooth enamel, which complicates orthodontic treatment due to weak enamel‐bracket bond strength. This case report presents a successful management of AI using fixed orthodontic appliances and prosthodontic rehabilitation. Amelogenesis imperfecta (AI) causes enamel defects, complicating oral hygiene, reducing masticatory function and lowering self‐esteem. This case report details an 18‐year‐old female with AI who underwent fixed orthodontic treatment followed by prosthodontic rehabilitation. The multidisciplinary approach restored function and aesthetics, significantly improving her quality of life. [ABSTRACT FROM AUTHOR]

Regional odontodysplasia (ROD) is a rare developmental disorder characterized by hypo-mineralization and hypoplasia of enamel and dentin. Symptoms include poorly developed tooth buds, delayed eruption of permanent teeth in affected quadrants, and ghost teeth. The affected teeth often become necrotic due to abnormal enamel and dentin development, making them susceptible to caries and infection. The aim of this case report is to describe the treatment of ROD through pulp revascularization. A 13-year-old girl was referred for endodontic treatment. The mandibular left incisors and first premolar, which were affected by regional odontodysplasia, lost their vitality because of the impaired structure of the enamel. Due to the teeth's early developmental stage, a regenerative endodontic treatment was attempted. All 3 teeth were treated using the same protocol following the AAE guidelines. After 4 weeks, treatment of the premolar was completed, whereas the incisor teeth remained symptomatic and were and therefore, intracanal dressing with calcium hydroxide was repeated and left in place for 5 months. Finally, the regenerative procedure was completed, and the crowns were restored. The patient was scheduled for follow-up examinations after 6 months, and then yearly for the next 3 years. After 1 year, the periapical lesion around the central incisor and premolar had resolved, the lesion around the apex of the lateral incisor was healing, and the roots had continued to develop. After 3 years, complete healing and pulp canal obliteration were observed in the central incisor and in the premolar. However, the root of the lateral incisor tooth was split, and it was recommended to extract this tooth. The positive outcomes of regenerative endodontics in the central incisor and premolar suggest that revascularization of the pulp may be optional for the treatment of immature necrotic teeth affected by developmental disorders, such as ROD, amelogenesis imperfecta, or dentinogenesis imperfecta. [ABSTRACT FROM AUTHOR]

Jalili syndrome (JS) (MIM#217080) is a rare autosomal recessive disorder with oculo‐dental malformations. The clinical phenotype is characterized by the presence of Cone‐Rod Dystrophy (CRD) and Amelogenesis Imperfecta (AI). Genetic mechanism entails a mutation in the CNNM4, a metal transporter gene located on Chromosome 2q11.2. A high fluoride concentration in groundwater has also been identified as an epigenetic factor in this syndrome. JS draws the attention of dentists due to its distinct oral manifestations. To the best of our knowledge, this is the first genetically confirmed pediatric case report from the Indian subcontinent emphasizing the clinical and radiographic features of this condition and its management in a 6‐year‐old child. [ABSTRACT FROM AUTHOR]

Enamel formation is a highly complex and regulated process. However, specific genetic mutations can cause dysregulation, resulting in defects in the enamel quantity, structure and composition. Inherited disorders such as amelogenesis imperfecta exclusively affect the formation of enamel. Nevertheless, enamel defects can also present as a feature of many inherited systemic diseases and syndromes. The defects present in a spectrum of mild to severe enamel pitting, mottling and loss of email, causing psychological and functional concerns for patients. Early diagnosis and intensive caries prevention along with a multidisciplinary specialist input are required in most cases. In this paper, we provide a comprehensive discussion of inherited enamel defects. [ABSTRACT FROM AUTHOR]

Introduction: : Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can commonly be classified into four primary groups. In this retrospective analysis, specific orofacial characteristics are described and associated with each of the AI types based on a patient cohort from Witten/Herdecke University, Germany. Methods: Data from 19 patients (ten male and nine female, mean age 12.27 ± 4.06 years) with AI who presented at the Department of Orthodontics between July 2011 and December 2023 were analyzed. Baseline skeletal and dental conditions were assessed, including the presence of hypodontia, displacements, and taurodontism. AI was classified into classes I–IV based on phenotype. Treatment needs were evaluated according to the main findings following the German KIG classification, while the radiological enamel situation was determined using panoramic radiographs. Results: An approximately equal distribution between classes II and III was found and a slight inclination toward a dolichofacial configuration (ΔML-NSL: 5.07 ± 9.23°, ΔML-NL: 4.24 ± 8.04°). Regarding orthodontic findings, disturbance in tooth eruption as well as open bite were the most prevalent issues (both 36.8%, n = 7). The most common AI classes were type I and II, which show an almost even distribution about the skeletal classes in sagittal dimension, while dolichofacial configuration was found most frequently in vertical dimension. Conclusion: Both clinical and radiological orthodontic findings in context with AI are subject to extensive distribution. It seems that no specific orofacial findings can be confirmed in association with AI with regard to the common simple classes I–IV. It may be more appropriate to differentiate the many subtypes according to their genetic aspects to identify possible associated orthodontic findings. [ABSTRACT FROM AUTHOR]

Aim: Loss‐of‐function mutations in FAM20A result in amelogenesis imperfecta IG (AI1G) or enamel‐renal syndrome, characterized by hypoplastic enamel, ectopic calcification, and gingival hyperplasia, with some cases reporting spontaneous tooth infection. Despite previous reports on the consequence of FAM20A reduction in gingival fibroblasts and transcriptome analyses of AI1G pulp tissues, suggesting its involvement in mineralization and infection, its role in deciduous dental pulp cells (DDP) remains unreported. The aim of this study was to evaluate the properties of DDP obtained from an AI1G patient, providing additional insights into the effects of FAM20A on the mineralization of DDP. Methodology: DDP were obtained from a FAM20A‐AI1G patient (mutant cells) and three healthy individuals. Cellular behaviours were examined using flow cytometry, MTT, attachment and spreading, colony formation, and wound healing assays. Osteogenic induction was applied to DDP, followed by alizarin red S staining to assess their osteogenic differentiation. The expression of FAM20A‐related genes, osteogenic genes, and inflammatory genes was analysed using real‐time PCR, Western blot, and/or immunolocalization. Additionally, STRING analysis was performed to predict potential protein–protein interaction networks. Results: The mutant cells exhibited a significant reduction in FAM20A mRNA and protein levels, as well as proliferation, migration, attachment, and colony formation. However, normal FAM20A subcellular localization was maintained. Additionally, osteogenic/odontogenic genes, OSX, OPN, RUNX2, BSP, and DSPP, were downregulated, along with upregulated ALP. STRING analysis suggested a potential correlation between FAM20A and these osteogenic genes. After osteogenic induction, the mutant cells demonstrated reduced mineral deposition and dysregulated expression of osteogenic genes. Remarkably, FAM20A, FAM20C, RUNX2, OPN, and OSX were significantly upregulated in the mutant cells, whilst ALP, and OCN was downregulated. Furthermore, the mutant cells exhibited a significant increase in inflammatory gene expression, that is, IL‐1β and TGF‐β1, whereas IL‐6 and NFκB1 expression was significantly reduced. Conclusion: The reduction of FAM20A in mutant DDP is associated with various cellular deficiencies, including delayed proliferation, attachment, spreading, and migration as well as altered osteogenic and inflammatory responses. These findings provide novel insights into the biology of FAM20A in dental pulp cells and shed light on the molecular mechanisms underlying AI1G pathology. [ABSTRACT FROM AUTHOR]

Objective: The aim of this review was to compare various types of restorations used in children and young adults affected with amelogenesis imperfecta (AI) to determine the most effective restorative treatment. Methods: This systematic review included randomized controlled trials, retrospective and prospective cohorts conducted on children and young adults diagnosed with amelogenesis imperfecta and written in French or English. A systematic search was conducted using four databases, namely Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Science Direct and Scopus, using a selection of MeSH terms: "Amelogenesis Imperfecta," "Therapeutics," "Treatment Outcome," "Adult, young," "Child," "Dental Restoration, Permanent," "Dental Restoration, Temporary," and "Esthetics, Dental." Results: Out of 138 articles identified in the initial search, four articles met all the inclusion criteria. The results showed that ceramic restorations had better quality scores and longevity compared to other restorations. Conclusion: Ceramic restorations could be considered the restorative treatment modality of choice for AI‐affected children and young adults. However, more high‐quality clinical trials involving young patients affected with AI are required to evaluate and compare the outcomes of different restorative approaches. Clinical Significance: Young patients affected with amelogenesis imperfecta usually suffer from low self‐esteem, psychological problems and social avoidance, caused by the alteration of teeth such as discoloration, sensitivity, fractures and reduced size. For the dentist, selecting the appropriate restorative treatment for AI in young patients could be a veritable challenge. Therefore, it is important to have an evidence‐based modality. For this reason, in this review, the different restorative approaches used in AI‐affected young patients were compared to recommend the most effective treatment. [ABSTRACT FROM AUTHOR]

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins. [ABSTRACT FROM AUTHOR]

Tooth eruption is an essential process for the development of the oral and maxillofacial system. Several inherited and acquired diseases might affect this tightly regulated process, resulting in premature, delayed, or even failed tooth eruption. The purpose of this article is to review the literature and the clinical parameters of metabolic bone diseases that affect tooth eruption. It examines the physiological aspects of tooth eruption and the pathophysiological changes induced by metabolic bone diseases, including changes in bone metabolism, density, and structure. The search strategy for this review included an electronic search in PubMed, Google Scholar, Medline, Scopus, and the Cochrane Library using the following keywords: "metabolic bone diseases", "tooth eruption", "delayed tooth eruption", and each reported disease in combination with "tooth eruption disorders", covering publications up to March 2024 and limited to English-language sources. Understanding the influence of metabolic bone diseases on tooth eruption is crucial for managing both dental and skeletal manifestations associated with these disorders. This review suggests that a multidisciplinary approach to treatment may significantly improve oral outcomes for patients suffering from such conditions. Clinicians should be aware of the specific dental abnormalities that may arise and consider comprehensive evaluations and individualized treatment plans. These findings underscore the need for further research into targeted therapies that address these abnormalities. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)–related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM -associated AI. [ABSTRACT FROM AUTHOR]

ABSTRACT Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by fragility of the skin and mucous membranes due to alterations in the dermal epidermal junction. This condition manifests as mechanically induced bullous lesions that heal with hypertrophic granulation tissue and/or atrophic scars. Here, we report two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp, which affects the N‐terminal end of the laminin‐332 (LM332) β3 chain, previously described in another JEB family sharing a common ethnic origin and LAMB3 haplotype with the siblings reported here. Moreover, all affected patients with p.Gly254Asp mutation from both families exhibits a distinct phenotype consisting of a few localized long‐standing skin lesions characterized by excessive granulation tissue formation or keloid scars, without new blistering, and associated with amelogenesis imperfecta. Our patients also showed nail dystrophy, expanding the phenotypic spectrum and confirming the peculiar role of the N‐terminal end of the β3 chain in regulating the granulation tissue response associated with the wound healing process. [ABSTRACT FROM AUTHOR]

Background: Amelogenesis Imperfecta (AI) is a disorder of tooth development characterized by abnormal enamel formation. In order to detect other dental and jawbone abnormalities that could be associated with AI, a retrospective and analytic study was conducted comparing panoramic radiographs of AI and non‐AI patients. Material and Methods: Digital panoramic radiographs of 60 AI and 60 non‐AI patients were examined. Abnormalities in dental number, size, shape, eruption, and in the shape of the dental arches were checked and blindly recorded by two experimented observers. Descriptive statistics using percentages and chi‐square test with.05 level of significance value was used. Results: Prevalence of supernumerary teeth, dental agenesis, microdontia, taurodontism, radicular dilacerations, dental inclusions, temporary teeth persistence, and pulp calcifications was significantly higher in AI patients compared to control patients. Prevalence of periapical images, cysts, and hypercementosis was lower in AI patients compared to control patients, with no statistically significant difference. A significant prevalence of mandibular hypoplasia was also noted in AI patients. Conclusion: In addition to enamel defect, panoramic radiography was useful in detecting other dental abnormalities and mandibular hypoplasia associated with AI and should therefore be systematically indicated for AI patients' care. [ABSTRACT FROM AUTHOR]

Background: Enamel renal syndrome is a rare genetic disorder transmitted through an autosomal recessive mode. It is featured by a hypoplastic amelogenesis imperfecta, delayed tooth eruption, gingival fibromatosis, and nephrocalcinosis. The aim of this study was to describe clinically, radiologically, and histologically the main features of enamel renal syndrome and to point out the role of dentists in early diagnosing this genetic disease. Materials and methods: Our case of enamel renal syndrome was initially described by clinical, radiographic, and genealogic data, then complemented by ultrasound examination of the kidneys and microscopic observation of gingivae. Results: The study showed the presence of amelogenesis imperfecta (AI), several teeth impaction, gingival hyperplasia, bilateral nephrocalcinosis, and multiple calcifications in pulp, gingiva, dental follicle, and kidneys. Conclusion: The patient was followed for a full mouth rehabilitation and also referred to a nephrology for global medical checkup. The dentist plays a key role in diagnosing genetic diseases and in referring patients for medical comprehensive care. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ege University School of Dentistry / Ege Üniversitesi Dis Hekimligi Fakültesi Dergisi is the property of Ege University Faculty of Dentistry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The resulting hypocalcemia may lead to dental abnormalities, such as enamel hypoplasia. The aim of this paper was to describe the full-mouth rehabilitation of a 15-year-old girl with chronic hypocalcemia due to a rare congenital hypoparathyroidism. Clinical considerations: In this patient, in the young adult dentition, conservative care was preferred. Onlays or stainless-steel crowns were performed on the posterior teeth, and direct or indirect (overlays and veneerlays) were performed on the maxillary premolars, canines, and incisors, using a digital wax-up. The mandibular incisors were bleached. The treatment clearly improved the patient's oral quality of life, with fewer sensitivities, better chewing, and aesthetic satisfaction. The difficulties were the regular monitoring and the limited compliance of the patient. Conclusion: Despite no clinical feedback in the literature, generalized hypomineralized/hypoplastic teeth due to hypoparathyroidism in a young patient can be treated as amelogenesis imperfecta (generalized enamel defects) with a conservative approach for medium-term satisfactory results. Highlights: This study provides new insights into the management of enamel hypoplasia caused by familial isolated hypoparathyroidism, helping to improve patient outcomes in similar cases. [ABSTRACT FROM AUTHOR]

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development. Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA). Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35). In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) represents a group of clinically and genetically heterogeneous disorders that affect enamel formation and mineralization. Although AI is commonly considered a monogenic disorder, digenic inheritance is rarely reported. In this study, we recruited two nonconsanguineous Chinese families exhibiting diverse phenotypes of enamel defects among affected family members. Digenic variants were discovered in both probands. In family 1, the proband inherited a paternal frameshift variant in LAMA3 (NM_198129.4:c.3712dup) and a maternal deletion encompassing the entire AMELX gene. This resulted in a combined hypoplastic and hypomineralized AI phenotype, which was distinct from the parents' manifestations. In family 2, whole‐exome sequencing analysis revealed the proband carried a maternal heterozygous splicing variant in COL17A1 (NC_000010.11 (NM_000494.3): c.4156 + 2dup) and compound heterozygous variants in RELT (paternal: NM_032871.4:c.260A > T; maternal: NM_032871.4:c.521 T > G). These genetic changes caused the abundant irregular enamel defects observed in the proband, whereas other affected family members carrying heterozygous variants in both COL17A1 and RELT displayed only horizontal grooves as their phenotype. The pathogenicity of the novel COL17A1 splice site variant was confirmed through RT‐PCR and minigene assay. This study enhances our understanding by highlighting the potential association between the co‐occurrence of variants in two genes and variable phenotypes observed in AI patients. [ABSTRACT FROM AUTHOR]

Objectives: To identify etiologic variants and perform deep dental phenotyping in patients with amelogenesis imperfecta (AI). Methods: Three patients of two unrelated families were evaluated. Genetic variants were investigated by exome and Sanger sequencing. An unerupted permanent third molar (AI1) from Patient1 and a deciduous first molar (AI2) from Patient2, along with three tooth‐type matched controls for each were characterized. Results: All three patients harbored biallelic pathogenic variants in FAM20A, indicating AI1G. Of the four identified variants, one, c.1231C > T p.(Arg411Trp), was novel. Patient1 possessed the largest deletion, 7531 bp, ever identified in FAM20A. In addition to hypoplastic enamel, multiple impacted teeth, intrapulpal calcification, pericoronal radiolucencies, malocclusion, and periodontal infections were found in all three patients, gingival hyperplasia in Patient1 and Patient2, and alveolar bone exostosis in Patient3. Surface roughness was increased in AI1 but decreased in AI2. Decreased enamel mineral density, hardness, and elastic modulus were observed in AI1 enamel and dentin and AI2 dentin, along with decreased phosphorus, increased carbon, and increased calcium/phosphorus and carbon/oxygen ratios. Severely collapsed enamel rods and disorganized dentin–enamel junction were observed. Conclusions: We report a novel FAM20A variant and, for the first time, the defective mineral composition and physical/mechanical properties of AI1G teeth. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Treatment of patients with amelogenesis imperfecta extends over many years, from childhood to early adulthood. Their management at any age is complex and has to be adapted in relation to therapies validated in the general population. [ABSTRACT FROM AUTHOR]

Background: Developmental defects of enamel (DDE) are a result of disturbances during formation and maturation of the enamel. Evaluating the most-cited DDE papers can provide important tools that point to the gaps and strengths of this important topic in dentistry. Summary: This bibliometric study analyzed the 100 most-cited papers on DDE. Using a combined keyword search strategy, the 100 most-cited papers were selected in the Web of Science Core Collection. Papers that addressed any type of DDE were included. The extracted data were title, number of citations, study theme, authorship, journal, type of DDE, type of dentition (primary or permanent), type of diagnosis, study design, year, and country of publication. The bibliometric networks were generated through VOSviewer software. The 100 papers had a range from 78 to 459 citations. The main themes of studies were etiopathogenesis (53%), prevalence and incidence (22%), and diagnosis (8%). The authors with the highest number of citations were Goodman AH and Rose JC (459 citations). Most articles were published in dental journals (47%). The most studied types of DDE were fluorosis and amelogenesis imperfecta in the permanent dentition (47%). Observational (24%) and non-systematic reviews (24%) were the most common study designs and ranged from 1977 to 2019. The country with the highest number of publications was the USA (41%). Key Messages: Most of the top 100 DDE papers were about fluorosis and amelogenesis imperfecta, with top papers from three continents with English as the native language. This topic is of great importance in dentistry, and the need for further studies is highlighted, especially regarding the diagnosis and treatment of some DDEs. [ABSTRACT FROM AUTHOR]

Background: KohlschüttereTönz syndrome (KTS), also called amelo‐cerebro‐hypohidrotic syndrome, is a very rare genetic condition, described for the first time by Kohlschutter, which typically manifests as a triad of symptoms: amelogenesis imperfecta, infantile onset epilepsy, and intellectual disability. 47 cases were reported in English language literature since 1974–2021. Case report: A 7‐year‐old girl was referred for dental evaluation. Oral examination revealed yellowish color of all the teeth due to enamel hypoplasia. The radiographic exam revealed a thin layer of enamel with decreased radiopacity of the enamel compared to that of dentin. The diagnosis of amelogenesis Imperfecta was established. In addition to that, the child's parents reported that she had spasticity, epileptic seizures and psychomotor developmental delay. The association of all these features leads us to conclude to KTS. Conclusion: It seems that numerous cases of KTS are still undiagnosed in the world, so this paper highlights the common clinical features of Kohlschütter‐Tönz Syndrome helping to an early diagnosis and more research about this condition. [ABSTRACT FROM AUTHOR]

Key Clinical Message Amelogenesis imperfecta (AI) is a rare developmental anomaly characterized by poorly developed or absent tooth enamel, which complicates orthodontic treatment due to weak enamel‐bracket bond strength. This case report presents a successful management of AI using fixed orthodontic appliances and prosthodontic rehabilitation. Abstract Amelogenesis imperfecta (AI) causes enamel defects, complicating oral hygiene, reducing masticatory function and lowering self‐esteem. This case report details an 18‐year‐old female with AI who underwent fixed orthodontic treatment followed by prosthodontic rehabilitation. The multidisciplinary approach restored function and aesthetics, significantly improving her quality of life.

Introduction: Amelogenesis imperfecta (AI) is a diverse collection of inherited diseases that show quantitative and qualitative defects in tooth enamel in the absence of systemic manifestations. Patients with AI often have open bite, which also requires complex care. In the final dental treatment, the focus should be on the preparation of indirect restorations, so early detection and care can be key factors for long-term success, as poor-quality enamel can be more easily attacked by caries. Case report: A 15-year-old young female patient presented to the Department of Prosthodontics of Semmelweis University in 2022 because of her worn down teeth due to amelogenesis imperfecta. The patient also had open bite. During the intraoral examination, reduced enamel was detected on all teeth, with partial enamel breakdown, exposing the dentin. Following the current professional recommendations, we planned monolithic zirconia crowns and splints as well as bridges to correct the tooth gaps on the upper and lower arches. In the first phase of the treatment, we increased the occlusal vertical dimension using a gothic arch tracer and digital face bow (Zebris for Ceramill). The impressions were taken by the 3Shape Trios 3 Pod, making it more comfortable for the patient and easier to copy accurately the increased occlusal vertical dimension from the temporary restoration to the final restoration. Due to the damaged tooth structure, for the final cementation resin modified glass ionomer was used. Protecting the monolithic zirconia restorations, the temporomandibular joint and the muscles, a Michigan-splint was created for the patient. Summary: For patients with AI, the appearance of the teeth can cause psychological and functional problems, so the goal of every treatment plan is restoration, and regular follow-up. Maintaining proper oral hygiene is also essential for patients with AI, and according to the literature, treatment with indirect restorations increases success compared to direct treatments.

Purpose: To evaluate the clinical performance of direct composite restorations using nanohybrid and nanofill composite materials in anterior teeth in patients with amelogenesis imperfecta (AI). Materials and Methods: The study included 15 patients with AI aged 14-30 years. During the study, the patients received anterior direct composite laminate veneer restorations using either a nanohybrid (Clearfil Majesty ES-2 and Clearfil Universal Bond, Kuraray Noritake) or a nanofill resin composite (Filtek Ultimate Universal Restorative and Single Bond Universal Adhesive, 3M Oral Care). The restorations were evaluated according to the modified USPHS criteria at baseline and at 1-, 2-, 3- and 4-year follow-up periods. Results: The cumulative success rate of anterior restorations was 80.5% for nanohybrid and 92.5% for nanofill composite after 4 years. Eight restorations with nanohybrid and three restorations with nanofill resin composites failed. Ten restorations failed due to fracture; the fracture rate was 12.3%. Statistically significant differences were found between nanohybrid and nanofill composites regarding marginal discoloration and surface texture after 3 years. Furthermore, statistically significant differences were observed with respect to color match after 4 years. Conclusion: The use of a nanohybrid or nanofill composite for anterior direct restorations in patients with AI was observed to be satisfactory, based on the rate of ideal and clinically acceptable restorations. The primary reason for restoration failure was fracture. The failure rate of nanohybrid composite restorations was higher than with nanofill composite restorations with respect to survival and marginal adaptation criteria. [ABSTRACT FROM AUTHOR]

Background: Amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are two groups of genetically inherited conditions resulting in abnormal enamel and dentin formation, respectively. Children and young people may be adversely affected by these conditions, with significant reduction in oral health related quality of life. Dental management of children with AI and DI is often complex, which is exacerbated by the absence of clear referral pathways and scarce evidence-based guidelines. Method: The need for increased knowledge and peer support led to the development of a group of UK paediatric dentists with a special clinical interest in the management of children with AI and DI. Purpose: The aims of this paper are to describe the establishment of an AI/DI Clinical Excellence Network (AI/DI CEN) in paediatric dentistry including outputs and future plans, and to share our collective learning to help support others anywhere in the world advance the care of people with AI or DI. [ABSTRACT FROM AUTHOR]

Introduction: Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar–incisor hypomineralization (MIH), a prevalent disease in children originating from environmental and epigenetic factors. MIH enamel presents as the abnormal enamel marked by loss of translucency, demarcation between the healthy and affected enamel, and reduced mineral content. The pathophysiology of opaque, demarcated enamel lesions is not understood; however, the retention of enamel proteins in the matrix has been suggested. Ameloblastin (Ambn) is an enamel protein of the secreted calciumbinding phosphoproteins (SCPPs) critical for enamel formation. When the Ambn gene is mutated or deleted, teeth are affected by hypoplastic amelogenesis imperfecta. Methods: In this study, enamel formation in mice was analyzed when transgenic Ambn was overexpressed from the amelogenin promoter encoding full-length Ambn. Ambn was under- and overexpressed at six increasing concentrations in separate mouse lines. Results: Mice overexpressing Ambn displayed opaque enamel at low concentrations and demarcated lesions at high concentrations. The severity of enamel lesions increased starting from the inner enamel close to the dentinoenamel junction (DEJ) to span the entire width of the enamel layer in demarcated areas. Associated with the opaque enamel were 17-kDa Ambn cleavage products, a prolonged secretory stage, and a thin basement membrane in the maturation stage. Ambn accumulations found in the innermost enamel close to the DEJ and the mineralization front correlated with reduced mineral content. Demarcated enamel lesions were associated with Ambn species of 17 kDa and higher, prolonged secretory and transition stages, a thin basement membrane, and shortened maturation stages. Hypomineralized opacities were delineated against the surrounding mineralized enamel and adjacent to ameloblasts detached from the enamel surface. Inefficient Ambn cleavage, loss of contact between ameloblasts, and the altered basement membrane curtailed the endocytic activity; thus, enamel proteins remained unresorbed in the matrix. Ameloblasts have the ability to distinguish between Ambn concentration and Ambn cleavage products through finely tuned feedback mechanisms. The under- or overexpression of Ambn in murine secretory ameloblasts results in either hypoplastic amelogenesis imperfecta or hypomineralization with opaque or sharply demarcated boundaries of lesions, similar to MIH. [ABSTRACT FROM AUTHOR]

Kohlschütter–Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and amelogenesis imperfecta. Here, we present a novel Rogdi mutant mouse deleting exons 6–11- a mutation found in KTS patients disabling ROGDI function. This Rogdi−/− mutant model recapitulates most KTS symptoms. Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility. Spontaneous locomotion and circadian activity tests demonstrate Rogdi mutant hyperactivity mirroring patient spasticity. Object recognition impairment indicates memory deficits. Rogdi−/− mutant enamel was markedly less mature. Scanning electron microscopy confirmed its hypomineralized/hypomature crystallization, as well as its low mineral content. Transcriptomic RNA sequencing of postnatal day 5 lower incisors showed downregulated enamel matrix proteins Enam, Amelx, and Ambn. Enamel crystallization appears highly pH-dependent, cycling between an acidic and neutral pH during enamel maturation. Rogdi−/− teeth exhibit no signs of cyclic dental acidification. Additionally, expression changes in Wdr72, Slc9a3r2, and Atp6v0c were identified as potential contributors to these tooth acidification abnormalities. These proteins interact through the acidifying V-ATPase complex. Here, we present the Rogdi−/− mutant as a novel model to partially decipher KTS pathophysiology. Rogdi−/− mutant defects in acidification might explain the unusual combination of enamel and rare neurological disease symptoms. [ABSTRACT FROM AUTHOR]

Enamel renal gingival syndrome is a rare clinical condition characterized by the presence of amelogenesis imperfecta hypoplastic type, gingival fibromatosis and delayed tooth eruption, in addition to nephrocalcinosis with normal blood calcium levels. It is inherited as an autosomal recessive trait caused by mutations in the FAM20A gene located on chromosome 17q24.2. The purpose of this report is to describe a case of enamel renal gingival syndrome and discuss its distinct features and management. [ABSTRACT FROM AUTHOR]

Amelogenesis Imperfecta (AI) is a rare genetic disease that affects the structure and appearance of the enamel. The etiology of AI can be various such as genetic, vitamin deficiency, local infection caused by trauma, birth defects, or idiopathic factors. Due to the fact that AI patients have thin layer of enamel, the treatment should cover all the surface and not alter or reduce the enamel structures. To cover all the teeth surface, preformed metal crowns (PMC) can be done by the technique called Hall technique. It is a method for managing primary molar with caries or other defects where the tooth is sealed under PMC without local anaesthesia, tooth preparation, and caries removal. An 8-year-old girl came to our attention showing yellowish teeth with rough surface, very sensitive to both cold and warm temperature on both upper and lower dentition. It was diagnosed as Amelogenesis Imperfecta. A complete treatment plan was carried. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI), an assemblage of genetic diseases with dental enamel malformations, is generally grouped into hypoplastic, hypomaturation, and hypocalcified types. This study aimed to identify the genetic etiology for a consanguineous Iranian family with autosomal recessive hypocalcified AI. Dental defects were characterized, and whole exome analysis conducted to search for disease-causing mutations. Minigene assay and RT-PCR were performed to evaluate molecular consequences of the identified mutation and expression of the causative gene in human dental tissues. The defective enamel of erupted teeth showed extensive post-eruptive failure and discoloration. Partial enamel hypoplasia and indistinct dentino-enamel junction were evident on unerupted teeth, resembling hypocalcified AI. A novel homozygous ODAPH (previously designated C4orf26) mutation of single-nucleotide deletion (NG_032974.1:g.5103del, NM_178497.5:c.67+1del) was identified to be disease-causing. The mutation would cause a frameshift to different ODAPH transcript variant (TV) products: p.(Ala23Hisfs∗29) for TV1 and p.(Gly23Aspfs∗140) for TV2. Both dental pulps of developing and exfoliating primary teeth expressed ODAPH TV2. Loss-of-function ODAPH mutations can cause AI type IIIB (the hypocalcified, autosomal recessive type), rather than type IIA4 (the hypomaturation, pigmented autosomal recessive type). This study supports a hypothesis that the product of ODAPH TV2 is the single dominant ODAPH protein isoform critical for dental enamel formation and may also play an unappreciated role in development and homeostasis of dentin-pulp complex. Due to genetic heterogeneity and a nonideal genotype-phenotype correlation of AI, it is essential to perform genetic testing for patients with inherited enamel defects to make a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To report two new cases with confirmed diagnosis of Heimler syndrome and describe their systemic and ophthalmic phenotype and visual rehabilitation. Methods: Retrospective review of medical records. Results: Both siblings were diagnosed as having sensori-neural hearing loss and retinal dystrophy with exuberant intraretinal cystoid spaces and cone–rod dysfunction. The older sibling also had amelogenesis imperfecta and neither had nail abnormalities. Genetic analysis identified homozygosity for the pathogenic variant c.2528G>A p.(Gly843Asp) in the PEX1 gene in both siblings. The parents were heterozygous carriers of the variant. Conclusions: The authors report a familial case of Heimler syndrome due to biallelic PEX1 pathogenic variants that manifested as macular dystrophy characterized by cone–rod dysfunction and complicated by intraretinal cystoid spaces. Review of the literature shows that ocular phenotype is variable in patients with Heimler syndrome. [J Pediatr Ophthalmol Strabismus. 2024;61(1):59–66.] [ABSTRACT FROM AUTHOR]

Objective: To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants. Methods: Whole-exome sequencing (WES) and Sanger sequencing were used to identify pathogenic gene variants in three Chinese families with amelogenesis imperfecta. Bioinformatics analysis, in vitro histological examinations and experiments were conducted to study the functional impact of gene variants, and the histological features of enamel, keratinised oral mucosa and dental follicle. Results: The authors identified two nonsense variants c. 406C > T (p.Arg136*) and c.826C > T (p.Arg176*) in a compound heterozygous state in family 1, two novel frameshift variants c.936dupC (p.Val313Argfs*67) and c.1483dupC (p.Leu495Profs*44) in a compound heterozygous state in family 2, and a novel homozygous frameshift variant c.530_531insGGTC (p.Ser178Valfs*21) in family 3. The enamel structure was abnormal, and psammomatoid calcifications were identified in both the gingival mucosa and dental follicle. The bioinformatics and subcellular localisation analyses indicated these variants to be pathogenic. The secondary and tertiary structure analysis speculated that these five variants would cause structural damage to FAM20A protein. Conclusion: The present results broaden the variant spectrum and clinical and histological findings of diseases associated with FAM20A, and provide useful information for future genetic counselling and functional investigation. [ABSTRACT FROM AUTHOR]