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Journal of Pediatric Ophthalmology and... 2024To report two new cases with confirmed diagnosis of Heimler syndrome and describe their systemic and ophthalmic phenotype and visual rehabilitation. (Review)
Review
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 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 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. .
Topics: Humans; Amelogenesis Imperfecta; Mutation; Siblings; Nails, Malformed; Phenotype; Eye Abnormalities; Pedigree; ATPases Associated with Diverse Cellular Activities; Membrane Proteins; Hearing Loss, Sensorineural
PubMed: 37092661
DOI: 10.3928/01913913-20230220-01 -
BDJ Open Apr 2023To characterize phenotype and genotype of amelogenesis imperfecta (AI) in a Thai patient, and review of literature.
OBJECTIVES
To characterize phenotype and genotype of amelogenesis imperfecta (AI) in a Thai patient, and review of literature.
MATERIALS AND METHODS
Variants were identified using trio-exome and Sanger sequencing. The ITGB6 protein level in patient's gingival cells was measured. The patient's deciduous first molar was investigated for surface roughness, mineral density, microhardness, mineral composition, and ultrastructure.
RESULTS
The patient exhibited hypoplastic-hypomineralized AI, taurodontism, and periodontal inflammation. Exome sequencing identified the novel compound heterozygous ITGB6 mutation, a nonsense c.625 G > T, p.(Gly209*) inherited from mother and a splicing c.1661-3 C > G from father, indicating AI type IH. The ITGB6 level in patient cells was significantly reduced, compared with controls. Analyses of a patient's tooth showed a significant increase in roughness while mineral density of enamel and microhardness of enamel and dentin were significantly reduced. In dentin, carbon was significantly decreased while calcium, phosphorus, and oxygen levels were significantly increased. Severely collapsed enamel rods and a gap in dentinoenamel junction were observed. Of six affected families and eight ITGB6 variants that have been reported, our patient was the only one with taurodontism.
CONCLUSION
We report the hypoplasia/hypomineralization/taurodontism AI patient with disturbed tooth characteristics associated with the novel ITGB6 variants and reduced ITGB6 expression, expanding genotype, phenotype, and understanding of autosomal recessive AI.
PubMed: 37041139
DOI: 10.1038/s41405-023-00142-y -
Children (Basel, Switzerland) Mar 2023Pediatric esthetic dentistry is a sensitive technique, as children can be less cooperative; hence, minimal appointments are preferred. The most conservative treatment...
Pediatric esthetic dentistry is a sensitive technique, as children can be less cooperative; hence, minimal appointments are preferred. The most conservative treatment modality for anterior esthetic rehabilitation is using direct composite veneer restorations. In many instances, esthetic improvements using composite resin are the only possible option until the growth phase of the pediatric patient is complete. In this article, we present three different case scenarios in young teenagers with different treatment needs requiring esthetic restorations. The first case report is a patient with amelogenesis imperfecta, the second is with generalized spacing, and the third is with localized microdontia. All three patients were followed up for six months post direct composite veneering and were highly satisfied with their treatment outcomes, which boosted their self-confidence.
PubMed: 36980104
DOI: 10.3390/children10030546 -
Frontiers in Physiology 2023The intracellular Ca2+ sensor stromal interaction molecule 1 (STIM1) is thought to play a critical role in enamel development, as its mutations cause Amelogenesis...
The intracellular Ca2+ sensor stromal interaction molecule 1 (STIM1) is thought to play a critical role in enamel development, as its mutations cause Amelogenesis Imperfecta (AI). We recently established an ameloblast-specific (AmelX-iCre) Stim1 conditional deletion mouse model to investigate the role of STIM1 in controlling ameloblast function and differentiation (Stim1 cKO). Our pilot data (Said et al., J. Dent. Res., 2019, 98, 1002-1010) support our hypothesis for a broad role of Stim1 in amelogenesis. This paper aims to provide an in-depth characterization of the enamel phenotype observed in our Stim1 cKO model. We crossed AmelX-iCre mice with Stim1-floxed animals to develop ameloblast-specific Stim1 cKO mice. Scanning electron microscopy, energy dispersive spectroscopy, and micro- CT were used to study the enamel phenotype. RNAseq and RT-qPCR were utilized to evaluate changes in the gene expression of several key ameloblast genes. Immunohistochemistry was used to detect the amelogenin, matrix metalloprotease 20 and kallikrein 4 proteins in ameloblasts. Stim1 cKO animals exhibited a hypomineralized AI phenotype, with reduced enamel volume, diminished mineral density, and lower calcium content. The mutant enamel phenotype was more severe in older Stim1 cKO mice compared to younger ones and changes in enamel volume and mineral content were more pronounced in incisors compared to molars. Exploratory RNAseq analysis of incisors' ameloblasts suggested that ablation of Stim1 altered the expression levels of several genes encoding enamel matrix proteins which were confirmed by subsequent RT-qPCR. On the other hand, RT-qPCR analysis of molars' ameloblasts showed non-significant differences in the expression levels of enamel matrix genes between control and -deficient cells. Moreover, gene expression analysis of incisors' and molars' ameloblasts showed that ablation caused changes in the expression levels of several genes associated with calcium transport and mitochondrial kinetics. Collectively, these findings suggest that the loss of in ameloblasts may impact enamel mineralization and ameloblast gene expression.
PubMed: 36935757
DOI: 10.3389/fphys.2023.1100714 -
Frontiers in Pediatrics 2022(solute carrier family 13, member 5) encodes sodium/citrate cotransporter, which mainly localizes in cellular plasma membranes in the frontal cortex, retina, and liver....
BACKGROUND
(solute carrier family 13, member 5) encodes sodium/citrate cotransporter, which mainly localizes in cellular plasma membranes in the frontal cortex, retina, and liver. Pathogenic variants of the gene cause an autosomal recessive syndrome known as "developmental and epileptic encephalopathy 25 with amelogenesis imperfecta."
RESULTS
Here, we have investigated six patients from three different consanguineous Saudi families. The affected individuals presented with neonatal seizures, developmental delay, and significant defects in tooth development. Some patients showed other clinical features such as muscle weakness, motor difficulties, intellectual disability, microcephaly, and speech problems in addition to additional abnormalities revealed by electroencephalography (EEGs) and magnetic resonance imaging (MRI). One of the MRI findings was related to cortical thickening in the frontal lobe. To diagnose and study the genetic defects of the patients, whole exome sequencing (WES) coupled with confirmatory Sanger sequencing was utilized. Iterative filtering identified two variants of , one of which is novel, in the families. Families 1 and 2 had the same insertion (a previously reported mutation), leading to a frameshift and premature stop codon. The third family had a novel splice site variant. Confirmatory Sanger sequencing corroborated WES results and indicated full segregation of the variants in the corresponding families. The patients' conditions were poorly controlled by multiple antiepileptics as they needed constant care.
CONCLUSION
Considering that recessive mutations are common in the Arab population, screening should be prioritized in future patients harboring similar symptoms including defects in molar development.
PubMed: 36923948
DOI: 10.3389/fped.2022.1051534 -
Heliyon Feb 2023To investigate the use of optical coherence tomography (OCT) as a tool to assess general and localised hypomineralisation defects in the enamel.
A pilot study comparing optical coherence tomography, radiography, clinical photography, and polarisation microscopy for studies of hypomineralisation disturbances in enamel.
AIM
To investigate the use of optical coherence tomography (OCT) as a tool to assess general and localised hypomineralisation defects in the enamel.
DESIGN AND MATERIALS
Ten extracted permanent teeth (four teeth with localised hypomineralisation, four teeth with general hypomineralisation, and two healthy controls) were used in this study. In addition, four participants who underwent OCT served as living controls for the extracted teeth.
METHODS
The OCT results were compared with clinical photographs, digital radiographs, and polarising microscopy images of tooth sections (considered the gold standard) to determine the method with the most accurate information regarding the extent of enamel disturbances: 1) visibility of enamel disturbance (visible yes/no); if yes, 2) extent of the disturbance in the enamel; and 3) determination of the plausible involvement of the underlying dentin.
RESULTS
OCT was more accurate than digital radiography and visual assessment. OCT could provide information about the extent of localised hypomineralised disturbances in the enamel that was comparable to that with polarisation microscopy of the tooth sections.
CONCLUSION
Within the limitations of this pilot study, it can be concluded that OCT is suitable for investigating and evaluating localised hypomineralisation disturbances; however, it is less useful in cases with generalised hypomineralisation of the enamel. In addition, OCT complements radiographic examination of enamel; however, more studies are necessary to elucidate the full extent of the use of OCT in case of hypomineralisation.
PubMed: 36865454
DOI: 10.1016/j.heliyon.2023.e13688 -
Journal of Personalized Medicine Feb 2023Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or...
Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and disease-causing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by defects.
PubMed: 36836560
DOI: 10.3390/jpm13020326 -
Cureus Dec 2022Amelogenesis imperfecta (AI) is a hereditary condition that affects the clinical features and structure of the enamel. The enamel formation diseases are inherited and...
Amelogenesis imperfecta (AI) is a hereditary condition that affects the clinical features and structure of the enamel. The enamel formation diseases are inherited and might be X-linked, autosomal dominant, recessive, sex-related, or sporadic. Dental professionals should evaluate such patients completely, both clinically and radiographically, to detect any cysts associated with impacted or unerupted teeth. This report describes the case of a 10-year-old patient affected by amelogenesis imperfecta with a dentigerous cyst involving an impacted tooth and an unerupted tooth of the maxilla.
PubMed: 36686148
DOI: 10.7759/cureus.32696 -
Materia Socio-medica 2023Dental anomalies (DAs) represent a significant chapter in pediatric dentistry with a lot of practical relevance. Both primary and permanent dentitions may be affected.
BACKGROUND
Dental anomalies (DAs) represent a significant chapter in pediatric dentistry with a lot of practical relevance. Both primary and permanent dentitions may be affected.
OBJECTIVE
The main objective of our study was to evaluate, using digital panoramic radiographs, the prevalence, distribution, and patterns of DAs in a sample of Lebanese children aged between 8 and 15 years old.
METHODS
112 digital panoramic radiographs of patients aged between 8 and 15 years (60 males and 52 females) from the year 2017 till 2022 attending the department of Pediatric Dentistry and Dental Public Health at the Faculty of Dental Medicine at the Lebanese University were assessed for DAs of number (hypodontia, oligodontia, hyperdontia), of size (microdontia, macrodontia), of shape (fusion, gemination, dilaceration, taurodontism), of position (transposition, ectopia, impaction), and of structure (dentin dysplasia, amelogenesis imperfecta, dentinogenesis imperfecta). The data were analyzed statistically using Chi-square and Fisher's exact tests.
RESULTS
Out of 112 patient radiographs, 84 showed at least one DA, which suggests a very high prevalence (75%). Among them, 36.9% exhibited multiple types of anomalies. These 84 patients showed a total of 274 DAs, distributed equally among males and females.
CONCLUSION
Dentists should be alerted to the presence of DAs. Their high prevalence requires careful clinical and radiological examinations for early detection. Regular monitoring is mandatory and could guide preventive approaches to minimize associated dental complications.
PubMed: 38380282
DOI: 10.5455/msm.2023.35.319-324 -
Proceedings of the National Academy of... Dec 2022The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the...
The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 µm (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 µm). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg and CO/Na) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. By revealing additional complexity at the rod/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.
Topics: Humans; Dental Caries; Crystallography; Amelogenesis Imperfecta; Amelogenesis; Dental Enamel
PubMed: 36534796
DOI: 10.1073/pnas.2211285119