-
Dentistry Journal May 2024Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The...
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.
PubMed: 38786528
DOI: 10.3390/dj12050130 -
International Dental Journal Apr 2024Correct identification and management of Developmental Defects of Enamel (DDEs) are essential to provide the best possible treatment. The present survey aims to...
OBJECTIVES
Correct identification and management of Developmental Defects of Enamel (DDEs) are essential to provide the best possible treatment. The present survey aims to investigate Italian dentists' knowledge of DDEs, their ability to recognise the different clinical pictures, and to choose the most appropriate clinical approach.
METHODS
A cross-sectional survey was planned based on a questionnaire including 27 closed-ended questions, and that proposed 4 clinical pictures, molar incisor hypomineralisation (MIH), amelogenesis imperfecta (AI), dental fluorosis (DF), and an initial caries lesion (ICL). It was distributed by e-mail to all Italian dentists (N = 63,883) through the Italian Federation of Doctors and Dentists. Discrete variables were expressed as absolute and relative frequencies (%). A multivariate analysis assessed whether socio-demographic variables correlated with the answers' truthfulness.
RESULTS
About 5017 questionnaires were included and analysed. Although 90.19% of the sample stated that they had received information on DDEs, a significant percentage did not recognise MIH (36.36%), AI (48.34%), DF (71.50%), and ICL (46.62%). Only 57.07% correctly classified enamel hypomineralisation as a qualitative defect, and even fewer, 54.45%, classified enamel hypoplasia as a quantitative defect. According to the logistic regressions, female dentists, dentists who treat mainly children and received information about DDEs, were more likely to recognise the 4 clinical pictures (P < .01).
CONCLUSIONS
Italian dentists showed many knowledge gaps on DDEs that need to be filled; those who received formal training were more capable of correctly identifying the defects and were more likely to prescribe an appropriate management approach for the defects.
CLINICAL SIGNIFICANCE
Increasing university courses and continuing education on diagnosing and managing DDEs seems reasonable to fill the knowledge gap on DDEs.
PubMed: 38679519
DOI: 10.1016/j.identj.2024.04.013 -
Scientific Reports Apr 2024Raine syndrome (RNS) is a rare autosomal recessive osteosclerotic dysplasia. RNS is caused by loss-of-function disease-causative variants of the FAM20C gene that encodes...
Raine syndrome (RNS) is a rare autosomal recessive osteosclerotic dysplasia. RNS is caused by loss-of-function disease-causative variants of the FAM20C gene that encodes a kinase that phosphorylates most of the secreted proteins found in the body fluids and extracellular matrix. The most common RNS clinical features are generalized osteosclerosis, facial dysmorphism, intracerebral calcifications and respiratory defects. In non-lethal RNS forms, oral traits include a well-studied hypoplastic amelogenesis imperfecta (AI) and a much less characterized gingival phenotype. We used immunomorphological, biochemical, and siRNA approaches to analyze gingival tissues and primary cultures of gingival fibroblasts of two unrelated, previously reported RNS patients. We showed that fibrosis, pathological gingival calcifications and increased expression of various profibrotic and pro-osteogenic proteins such as POSTN, SPARC and VIM were common findings. Proteomic analysis of differentially expressed proteins demonstrated that proteins involved in extracellular matrix (ECM) regulation and related to the TGFβ/SMAD signaling pathway were increased. Functional analyses confirmed the upregulation of TGFβ/SMAD signaling and subsequently uncovered the involvement of two closely related transcription cofactors important in fibrogenesis, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Knocking down of FAM20C confirmed the TGFβ-YAP/TAZ interplay indicating that a profibrotic loop enabled gingival fibrosis in RNS patients. In summary, our in vivo and in vitro data provide a detailed description of the RNS gingival phenotype. They show that gingival fibrosis and calcifications are associated with, and most likely caused by excessed ECM production and disorganization. They furthermore uncover the contribution of increased TGFβ-YAP/TAZ signaling in the pathogenesis of the gingival fibrosis.
Topics: Humans; Transforming Growth Factor beta; Gingiva; Signal Transduction; Proteomics; Fibrosis; YAP-Signaling Proteins; Osteosclerosis; Adaptor Proteins, Signal Transducing; Transcription Factors; Dental Enamel Hypoplasia; Fibroblasts; Microcephaly; Female; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Male; Trans-Activators; Intracellular Signaling Peptides and Proteins; Casein Kinase I; Extracellular Matrix Proteins; Amelogenesis Imperfecta; Cells, Cultured; Abnormalities, Multiple; Cleft Palate; Exophthalmos
PubMed: 38664418
DOI: 10.1038/s41598-024-59713-0 -
The Chinese Journal of Dental Research Mar 2024To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants.
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.
Topics: Humans; Amelogenesis Imperfecta; Calcification, Physiologic; Computational Biology; Dental Enamel; Dental Enamel Proteins; East Asian People
PubMed: 38546520
DOI: 10.3290/j.cjdr.b5136761 -
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 -
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 Apr 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.
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