FAM20A-Associated Amelogenesis Imperfecta: Gene Variants with Functional Verification and Histological Features.

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.

Establishment of a clinical network for children with amelogenesis imperfecta and dentinogenesis imperfecta in the UK: 4-year experience.

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.

Renal tubular estrogen ß receptors are expressed at high levels in small vessel vasculitis and are primarily localized in the distal tubule.

This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were investigated in antineutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis and immunoglobulin A (IgA) nephropathy groups, which are small vessel vasculitis subtypes with two different glomerulonephritis development pathophysiologies. The design of this study was prepared as a retrospective cohort study. The study included 42 patients with ANCA-associated vasculitis and 18 with IgA nephropathy in the small vessel vasculitis group. For the control group, intact renal tissues of 28 patients who underwent nephrectomy due to renal cell carcinoma were used. Renal biopsy samples of the groups were stained with ER beta (ß) and ER alpha (α). Tubular ER ß expression score (TERßES) median values were found to be significantly higher in ANCA- associated vasculitis (B = 0.724, OR [95%CI]: 2.064 [1.141-3.731], p = .016) and IgA nephropathy (B = 0.898, OR [95%CI]: 2.454 [1.307-4.609], p = .005) than in intact kidney tissue. It was determined that tubular ERß was most frequently localized in the distal tubule at 57.9% and the second most common in the proximal tubule at 20.4%. The expression of tubular ERß is increased in glomerulonephritis due to small vessel vasculitis. Tubular ERßs are most commonly localized in the distal tubule. Further studies are needed to understand the physiological and pathophysiological effects of altered renal ER levels in small vessel vasculitis.

The Rogdi knockout mouse is a model for Kohlschütter-Tönz syndrome.

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.

Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants.

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.].

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Digenic inheritance accounts for phenotypic variability in amelogenesis imperfecta.

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.

Deep dental phenotyping and a novel FAM20A variant in patients with amelogenesis imperfecta type IG.

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.

Developmental Defects of Enamel: A Bibliometric Analysis of the Top 100 Most-Cited Papers.

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.

Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine.

BACKGROUND: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine. CASE PRESENTATION: We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine. CONCLUSION: To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome.

Perampanel effectiveness in treating ROGDI-related Kohlschütter-Tönz syndrome: first reported case in China and literature review.

PURPOSE: This study reported the first case of Kohlschütter-Tönz syndrome (KTS) in China and reviewed the literature of the reported cases. METHODS: This patient was registered at the Children's Hospital of Chongqing Medical University. The patient's symptoms and treatments were recorded in detail, and the patient was monitored for six years. We employed a combination of the following search terms and Boolean operators in our search strategy: Kohlschütter-Tönz syndrome, KTS, and ROGDI. These terms were carefully selected to capture a broad range of relevant publications in PubMed, Web of Science, WHO Global Health Library, and China National Knowledge Infrastructure, including synonyms, variations, and specific terms related to KTS. The pathogenicity of the variants was predicted using SpliceAI and MutationTaster, and the structures of the ROGDI mutations were constructed using I-TASSER. RESULTS: This is the first case report of KTS in China. Our patient presented with epilepsy, global developmental delay, and amelogenesis imperfecta. A trio-WES revealed homozygous mutations in ROGDI (c.46-37_46-30del). The brain magnetic resonance imaging (MRI) and video electroencephalogram (VEEG) were normal. The efficacy of perampanel (PMP) in treating seizures and intellectual disability was apparent. Furthermore, 43 cases of ROGDI-related KTS were retrieved. 100% exhibited epilepsy, global developmental delay, and amelogenesis imperfecta. 17.2% received a diagnosis of attention deficit hyperactivity disorder (ADHD), and 3.4% were under suspicion of autism spectrum disorder (ASD). Language disorders were observed in all patients. Emotional disorders, notably self-harm behaviors (9.1%), were also reported. CONCLUSION: ROGDI-related KTS is a rare neurodegenerative disorder, characterized by three classic clinical manifestations: epilepsy, global developmental delay, and amelogenesis imperfecta. Moreover, patients could present comorbidities, including ADHD, ASD, emotional disorders, and language disorders. PMP may be a potential drug with relatively good efficacy, but long-term clinical trials are still needed.

A Review of Selected Dental Anomalies With Histologic Features in the Pediatric Patient.

Unique dental conditions in children include odontogenic cysts and tumors, hereditary dental diseases, developmental anomalies, and lesions associated with the eruption of the primary or permanent teeth. Many of these conditions have long lasting effects on the adult dentition in terms of affecting esthetics, function, and overall quality of life. Inherited dental syndromes affect the dental hard tissues specifically the enamel, dentin, and/or cementum in a generalized manner, involving both primary and permanent teeth. These conditions manifest in altered quality or quantity of the hard tissues, leading to fragility, tooth loss and dental diseases such as caries, periapical pathology, and periodontal disease. This category includes amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasia, hypophosphatasia, and hypophosphatemia. Developmental defects such as regional odontodysplasia are defined by involvement of the primary and permanent dentition in a localized manner, identified in early childhood. This review will elaborate on the histologic findings in these selected dental conditions with a discussion on clinical and radiographic findings, as well as molecular features wherever appropriate.

Splicing mutations in AMELX and ENAM cause amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations are reported to be relevant to AI. However, the mechanism underlying AI caused by different mutations is still unclear. This study aimed to reveal the molecular pathogenesis in AI families with 2 novel pre-mRNA splicing mutations. METHODS: Two Chinese families with AI were recruited. Whole-exome sequencing and Sanger sequencing were performed to identify mutations in candidate genes. Minigene splicing assays were performed to analyze the mutation effects on mRNA splicing alteration. Furthermore, three-dimensional structures of mutant proteins were predicted by AlphaFold2 to evaluate the detrimental effect. RESULTS: The affected enamel in family 1 was thin, rough, and stained, which was diagnosed as hypoplastic-hypomature AI. Genomic analysis revealed a novel splicing mutation (NM_001142.2: c.570 + 1G > A) in the intron 6 of amelogenin (AMELX) gene in family 1, resulting in a partial intron 6 retention effect. The proband in family 2 exhibited a typical hypoplastic AI, and the splicing mutation (NM_031889.2: c.123 + 4 A > G) in the intron 4 of enamelin (ENAM) gene was observed in the proband and her father. This mutation led to exon 4 skipping. The predicted structures showed that there were obvious differences in the mutation proteins compared with wild type, leading to impaired function of mutant proteins. CONCLUSIONS: In this study, we identified two new splicing mutations in AMELX and ENAM genes, which cause hypoplastic-hypomature and hypoplastic AI, respectively. These results expand the spectrum of genes causing AI and broaden our understanding of molecular genetic pathology of enamel formation.

How to optimize bonding procedures on healthy and hypomineralized enamel in orthodontics? / Comment optimiser les procédures de collage sur l'émail sain et hypominéralisé en orthodontie ?

Introduction: Bonding to enamel is a daily problem for the orthodontist. While bonding to healthy enamel is nowadays well mastered, bonding to hypomineralized enamel is much less so. The aim of this article was to help the orthodontist to optimise bonding, whatever the clinical situation. Material and Method: Based on data from the literature, the clinical and microscopic characteristics of healthy and hypomineralised enamel, including amelogenesis imperfecta (AI), molar incisor hypomineralization (MIH), fluorosis or erosion will be described. Proposals for optimising bonding will then be identified and summarized. Results: Bonding to enamel is reliable, but the use of an etch-and-rinse mode (even with a universal adhesive) is recommended. For AI, MIH and fluorosis, the use of sodium hypochlorite after etching seems to significantly increase bonding. No treatment is needed for eroded enamel. However, deep resin infiltration for severe MIH or superficial resin infiltration for fluorosis would reduce the risk of enamel fracture during bracket removal. Conclusion: It is important to be aware of the characteristics of the dental substrate and the materials used to optimize procedures.

Introduction: L'adhésion à l'émail est une problématique quotidienne de l'orthodontiste. Si le collage à l'émail sain est aujourd'hui maîtrisé, celui sur l'émail hypominéralisé l'est beaucoup moins. L'objectif de cet article était d'aider l'orthodontiste à optimiser son collage, quelle que soit la situation clinique. Matériel et méthode: À partir des données issues de la littérature, les caractéristiques clinique et microscopique de l'émail sain et de l'émail hypominéralisé en cas d'amélogenèse imparfaite (AI), d'hypominéralisation de molaire incisive (MIH), de fluorose ou d'érosion seront décrites. Puis, les propositions d'optimisation du collage seront recensées et synthétisées. Résultats: Le collage à l'émail est fiable, mais l'utilisation d'un mode mordançage-rinçage (même avec un adhésif universel) est conseillée. Pour l'AI, la MIH et la fluorose, l'utilisation d'hypochlorite de sodium après mordançage semble significativement augmenter l'adhérence. Aucun traitement n'est nécessaire pour l'émail érodé. Cela dit, une infiltration de résine en profondeur pour les MIH sévères ou superficielles pour la fluorose permettrait de réduire le risque de fracture d'émail à la dépose de l'attache. Conclusion: Il convient de connaître les caractéristiques du substrat sur lequel on colle et celles des matériaux utilisés pour optimiser ses procédures.

Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease.

Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis1. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta2. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency3,4, and in patients diagnosed with coeliac disease5-7. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.

Misdiagnosed metabolic bone abnormality: a case report.

BACKGROUND: Metabolic bone disease causes significant morbidity and mortality, especially when misdiagnosed. With genetic testing, multiple disease pathologies can be analyzed. CASE PRESENTATION: A 5-year and 9-month-old otherwise healthy Yemeni girl presented to her Yemen physician for evaluation of inward bending of her right knee and short stature. After extensive medical testing, she was given a diagnosis of hypophosphatemic rickets and growth hormone deficiency and started on treatment. Despite appropriate treatment, however, her condition continued to progress, prompting her family to pursue additional workup including genetic testing outside of Yemen. Genetic testing ultimately revealed a variation of unknown significance associated with amelogenesis imperfecta. CONCLUSIONS: Hypophosphatemic rickets secondary to renal tubular acidosis was the working diagnosis. However, the patient's condition did not improve. Further genetic testing revealed a variation of unknown significance associated with amelogenesis imperfecta. We aim to present this case, provide an overview of the causes, and diagnostic metabolic bone health evaluation.

Oro-dental phenotyping and report of three families with RELT-associated amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of rare genetic conditions characterized by quantitative and/or qualitative tooth enamel alterations. AI can manifest as an isolated trait or as part of a syndrome. Recently, five biallelic disease-causing variants in the RELT gene were identified in 7 families with autosomal recessive amelogenesis imperfecta (ARAI). RELT encodes an orphan receptor in the tumor necrosis factor (TNFR) superfamily expressed during tooth development, with unknown function. Here, we report one Brazilian and two French families with ARAI and a distinctive hypomineralized phenotype with hypoplastic enamel, post-eruptive enamel loss, and occlusal attrition. Using Next Generation Sequencing (NGS), four novel RELT variants were identified (c.120+1G>A, p.(?); c.120+1G>T, p.(?); c.193T>C, p.(Cys65Arg) and c.1260_1263dup, p.(Arg422Glyfs*5)). Our findings extend the knowledge of ARAI dental phenotypes and expand the disease-causing variants spectrum of the RELT gene.

[Analysis of amelogenesis imperfecta with abnormal tooth eruption caused by FAM83H mutation].

Objective: FAM83H is one of the major pathogenic genes of amelogenesis imperfecta (AI). Previous studies focused on the abnormal enamel development and mineralization caused by the mutations in FAM83H. Here we aimed to observe other effects of FAM83H mutations on tooth eruption besides AI through clinical case analysis. Methods: Published AI cases with FAM83H mutations were searched through PubMed database, and the characteristics of tooth eruption of each cases were counted and analyzed. The literature search range was from January 1, 2008 to February 28, 2023, using the keywords FAM83H and amelogenesis imperfecta. The included literature must provide the detailed radiographic imaging or dental eruption information of AI patients, as well as FAM83H gene mutation information. The basic clinical information, tooth phenotypes, and mutations of all the enrolled cases were collected and analyzed in order to find the characteristics of abnormal tooth eruption. Results: Among 45 papers about FAM83H related to AI, twenty meeting the inclusion criteria were selected, involving 50 AI patients carrying FAM83H mutations who had radiographic image data or the detailed description of tooth eruption. A total of 34 abnormal erupted teeth were from 12 patients (12/50, 24%), among which 85% (29/34) had clear eruption path without any eruption obstructions, either embedded (25/34, 74%) or partially erupted (4/34, 12%). Tooth position analysis found that abnormal eruption of canines and second molars accounted for the highest proportion, accounting for 38% (13/34) respectively. Conclusions: The mutations in FAM83H may lead to amelogenesis imperfecta as well as abnormal tooth eruption at specific tooth positions.