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Clinical Case Reports Mar 2024Treatment 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...
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.
PubMed: 38523819
DOI: 10.1002/ccr3.8704 -
BMC Oral Health Mar 2024Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical...
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.
Topics: Animals; Humans; Child; Female; Pregnancy; Dental Enamel Hypoplasia; Fluorides; Prenatal Exposure Delayed Effects; Dental Enamel; Phenols; Prevalence
PubMed: 38468230
DOI: 10.1186/s12903-023-03786-2 -
Cureus Feb 2024This clinical case report details the comprehensive diagnosis and dental management of a seven-year-old female patient diagnosed with the rare genetic disorder,...
This clinical case report details the comprehensive diagnosis and dental management of a seven-year-old female patient diagnosed with the rare genetic disorder, amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS). The case initially presented as congenital adrenal hyperplasia and amelogenesis imperfecta, but further genetic analysis revealed the involvement of AIGFS due to a mutation in the gene. Diagnosis, confirmed through whole exome sequencing, clinical assessment, and laboratory tests, necessitated a multidisciplinary approach to address the treatment of such cases. The article underscores the critical importance of diagnosing and managing dental manifestations in pediatric patients with complex genetic conditions, highlighting the difficulties of treating AIGFS in mixed dentition. This case also highlights the indispensable role of pediatric dentists in diagnosing and treating these cases, ultimately improving the quality of life for individuals with AIGFS.
PubMed: 38465125
DOI: 10.7759/cureus.53787 -
Journal of Medical Genetics Jun 2024Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical...
BACKGROUND
Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic and variants have so far been associated with Mendelian genetic disease.
METHODS
Eight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice.
RESULTS
Rare biallelic pathogenic variants in plexin B2 (), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. expression was detected in differentiating ameloblasts.
CONCLUSION
We identify rare biallelic pathogenic variants in as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in knockout mice, and, together with the rarity of human variants, may explain why pathogenic variants in have not been reported previously.
Topics: Humans; Animals; Male; Female; Mice; Intellectual Disability; Pedigree; Amelogenesis Imperfecta; Receptors, Cell Surface; Nerve Tissue Proteins; Alleles; Child; Hearing Loss; Hearing Loss, Sensorineural; Adult; Mutation; Adolescent; Child, Preschool; Phenotype
PubMed: 38458752
DOI: 10.1136/jmg-2023-109728 -
European Archives of Paediatric... Feb 2024Amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are two groups of genetically inherited conditions resulting in abnormal enamel and dentin formation,...
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.
Topics: Child; Humans; Adolescent; Amelogenesis Imperfecta; Dentinogenesis Imperfecta; Quality of Life; Dentin; United Kingdom
PubMed: 38308725
DOI: 10.1007/s40368-023-00859-2 -
Journal of Dental Sciences Jan 2024Amelogenesis imperfecta (AI), an assemblage of genetic diseases with dental enamel malformations, is generally grouped into hypoplastic, hypomaturation, and...
BACKGROUND/PURPOSE
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.
MATERIALS AND METHODS
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.
RESULTS
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 (previously designated ) 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 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 TV2.
CONCLUSION
Loss-of-function 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 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.
PubMed: 38303846
DOI: 10.1016/j.jds.2023.09.020 -
Revista Cientifica Odontologica... 2023The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this...
The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this condition in various ways. The present clinical case from the Teaching Dental Clinic of the Peruvian University Cayetano Heredia is of a 6-year 5-month-old male child who came to the dental office accompanied by his father and 8-year-old sister, diagnosed with the same AI condition. The comprehensive treatment proposed for this patient was determined by radiographic and clinical examinations and consultations with specialists in different areas. The purpose of this publication was to report a case and describe possible clinical approaches.
PubMed: 38288452
DOI: 10.21142/2523-2754-1102-2023-156 -
Frontiers in Physiology 2023Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar-incisor...
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 calcium-binding phosphoproteins (SCPPs) critical for enamel formation. When the gene is mutated or deleted, teeth are affected by hypoplastic amelogenesis imperfecta. In this study, enamel formation in mice was analyzed when transgenic was overexpressed from the amelogenin promoter encoding full-length Ambn. was under- and overexpressed at six increasing concentrations in separate mouse lines. Mice overexpressing 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 dentino-enamel 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.
PubMed: 38274050
DOI: 10.3389/fphys.2023.1233391 -
Iranian Journal of Biotechnology Oct 2023Dental enamel formation is a complex process that is regulated by various genes. One such gene, Family With Sequence Similarity 83 Member H (Fam83h), has been identified...
BACKGROUND
Dental enamel formation is a complex process that is regulated by various genes. One such gene, Family With Sequence Similarity 83 Member H (Fam83h), has been identified as an essential factor for dental enamel formation. Additionally, Fam83h has been found to be potentially linked to the Wnt/β-catenin pathway.
OBJECTIVES
This study aimed to investigate the effects of the Fam83h knockout gene on mineralization and formation of teeth, along with mediators of the Wnt/β-catenin pathway as a development aspect in mice.
MATERIALS AND METHODS
To confirm the Fam83h-KnockOut mice, both Sanger sequencing and Western blot methods were used. then used qPCR to measure the expression levels of genes related to tooth mineralization and formation of dental root, including Fam20a, Dspp, Dmp1, Enam, Ambn, Sppl2a, Mmp20, and Wnt/β-catenin pathway mediators, in both the Fam83h-Knockout and wild-type mice at 5, 11 and 18 days of age. also the expression level of Fgf10 and mediators of the Wnt/β-catenin pathway was measured in the skin of both Knockout and wild-type mice using qPCR. A histological assessment was then performed to further investigate the results.
RESULTS
A significant reduction in the expression levels of Ambn, Mmp20, Dspp, and Fgf10 in the dental root of Fam83h-Knockout mice compared to their wild-type counterparts was demonstrated by our results, indicating potential disruptions in tooth development. Significant down-regulation of CK1a, CK1e, and β-catenin in the dental root of Fam83h-Knockout mice was associated with a reduction in mineralization and formation-related gene. Additionally, the skin analysis of Fam83h-Knockout mice revealed reduced levels of Fgf10, CK1a, CK1e, and β-catenin. Further histological assessment confirmed that the concurrent reduction of Fgf10 expression level and Wnt/β-catenin genes were associated with alterations in hair follicle maturation.
CONCLUSIONS
The concurrent reduction in the expression level of both Wnt/β-catenin mediators and mineralization-related genes, resulting in the disruption of dental mineralization and formation, was caused by the deficiency of Fam83h. Our findings suggest a cumulative effect and multi-factorial interplay between Fam83h, Wnt/Β-Catenin signaling, and dental mineralization-related genes subsequently, during the dental formation process.
PubMed: 38269199
DOI: 10.30498/ijb.2023.391902.3673 -
The Journal of Clinical Pediatric... Jan 2024Despite efforts to promote breastfeeding, many babies aged <6 months receive only baby formula reconstituted with bottled water. The intake of high levels of fluoride...
Despite efforts to promote breastfeeding, many babies aged <6 months receive only baby formula reconstituted with bottled water. The intake of high levels of fluoride during amelogenesis has been associated with hypomineralization of the tooth enamel, with aesthetic and mechanical repercussions. The objective of this study was to determine the potential risk of dental fluorosis associated with baby formulas marketed in Spain. We measured 26 baby formulas frequently consumed in Spain; 17 brands for babies aged <6 months, 5 for those aged >6 months, and 4 ready-to-use brands. They were prepared with 4 types of water: distilled water and three brands of bottled water with different levels of fluoride. The fluoride concentration (mg/L or ppm F) was measured with an ion-specific electrode coupled to an ion analyzer. Each sample was prepared according to the manufacturer's instructions and analyzed in triplicate. A descriptive analysis was carried out. The minimum fluoride level found was 0.04 mg/L and the maximum was 1.02 mg/L. Considering the daily intake of these formulas, none exceeded the clinically-acceptable daily dose limit risk for fluorosis (0.07 mg F/day/kg body weight) when mixed with bottled water with a low level of fluoride (0.1 mg/L). However, when the same brands of formula were reconstituted with bottled water with a higher fluoride content (0.99 mg/L), they all exceeded the daily dose limit for the risk of fluorosis. As the potential risk of dental fluorosis associated with the formulas tested depends exclusively on the fluoride concentration of the waters used for reconstitution, formula packaging should contain a warning.
Topics: Infant; Humans; Infant Formula; Fluorides; Fluorosis, Dental; Drinking Water; Spain; Water Supply
PubMed: 38239163
DOI: 10.22514/jocpd.2024.013