Characteristics of oral health of patients with X-linked hypophosphatemia: case reports and literature review.

BACKGROUND: Oral health is impaired in X-linked hypophosphatemia (XLH), resulting in delayed dental development, malocclusion, and radiographic abnormalities. This study investigates the oral manifestations in Slovenian XLH patients, focusing on enamel and dentin abnormalities and a literature review of spontaneous periapical abscesses in XLH cases. OBJECTIVES: To report XLH patients with specific oral signs and symptoms, histological analysis of affected teeth, and review of reported cases of XLH patients with spontaneous periapical abscesses. METHODS: Case reports: Seven XLH patients from the National Registry of Patients with Rare Diseases underwent a detailed oral examination, including X-ray reviews. The patients who were expected to have tooth exfoliation or extraction were asked to donate their teeth for histological analysis by scanning electron microscopy. LITERATURE SEARCH: A literature search of four electronic databases and a manual bibliography search aimed to identify documented cases of XLH with periapical abscesses up to January 21, 2024. Inclusion criteria were confirmed XLH patients with periapical abscesses in English peer-reviewed publications. RESULTS: Tooth samples from three XLH patients showed reduced dentin mineralisation, affecting one-third to one-half of the outer dentin. Inadequate mineralisation, uneven dentin tubules, and cracks and chipping in the enamel were observed, indicating mineralisation deviations. Similar cracks extended into the dentin and were also present in the root of the examined tooth. Based on the content of the 75 items identified in the search, spontaneous abscesses are not uncommon in patients with XLH. CONCLUSIONS: XLH significantly affects patients' lives and requires lifelong treatment. Dental examinations consistently revealed oral problems, including malocclusion. Histological analysis confirmed structural changes, especially in the dentin. Despite continued treatment, XLH patients may have an increased risk of oral pathologies. Further research is needed to understand the impact of XLH and its treatment on dental health.

The Development and Evaluation of the Slovenian Version of the Early Childhood Oral Health Impact Scale (ECOHIS-SVN).

Introduction: There has been no valid and reliable instrument available to measure the impact of oral health on the quality of life of Slovenian preschool children. The main aim of this study was to develop and evaluate the validity and reliability of the first Slovenian instrument assessing Oral Health-Related Quality of Life (OHRQoL) preschool children: the ECOHIS-SVN. Methods: The ECOHIS-SVN was developed using forward-backward translations and with the participation of children aged under six and their parents. The children's teeth were examined, and parents were asked to complete questionnaires, including the ECOHIS-SVN. The internal consistency of ECOHIS-SVN was evaluated through the calculation of Cronbach's alpha (α), test-retest reliability with an intra-class-correlation coefficient (ICC), convergent validity with Spearman's rank correlation (r) and criterion validity with the Mann-Whitney test. The association between the ECOHIS-SVN score and parents' age, educational level, self-reported oral health and OHIP-SVN14 was estimated using multiple linear regression. Results: In the study, 255 children participated, with a mean age of 4.8 years (±0.8). The ECOHIS-SVN questionnaire was completed by the parents of all 255 children and re-filled by 71 parents. The results of the total ECOHIS-SVN scale include α=0.85, ICC=0.85, and r=0.6-0.75. A statistically significant association was found between the ECOHIS-SVN and parents' age and between the ECOHIS-SVN and parents' OHIP-SVN14 in the whole group and in the subgroup of children with no teeth affected by cavitated caries (dmft=0) (p=0.025, p=0.028), respectively. Conclusion: ECOHIS-SVN enables further studies to assess the OHRQoL of preschool children in the Slovenian-speaking population.

An Intron c.103-3T>C Variant of the AMELX Gene Causes Combined Hypomineralized and Hypoplastic Type of Amelogenesis Imperfecta: Case Series and Review of the Literature

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders of dental enamel. X-linked AI results from disease-causing variants in the AMELX gene. In this paper, we characterise the genetic aetiology and enamel histology of female AI patients from two unrelated families with similar clinical and radiographic findings. All three probands were carefully selected from 40 patients with AI. In probands from both families, scanning electron microscopy confirmed hypoplastic and hypomineralised enamel. A neonatal line separated prenatally and postnatally formed enamel of distinctly different mineralisation qualities. In both families, whole exome analysis revealed the intron variant NM_182680.1: c.103-3T>C, located three nucleotides before exon 4 of the AMELX gene. In family I, an additional variant, c.2363G>A, was found in exon 5 of the FAM83H gene. This report illustrates a variant in the AMELX gene that was not previously reported to be causative for AI as well as an additional variant in the FAM83H gene with probably limited clinical significance.

Dataset on amelogenesis-related genes variants (ENAM and ENAM interacting genes) and on human leukocyte antigen alleles (DQ2 and DQ8) distribution in children with and without molar-incisor hypomineralisation (MIH).

All children, who were born in 2004 and had undergone surgical treatment for recurrent acute tonsillitis and/or acute otitis media at the ear, nose and throat clinic (ENT) between 2004 and 2010, were called on dental examination and blood sampling. Out of 441 invitees, 113 children and their parents/legal guardians agreed to participate. The following data from this group of subjects are presented: the presence of clinical signs of molar-incisor hypomineralisation (MIH), the distribution of human leukocyte antigen (HLA) alleles DQ2 and DQ8 and eight single nucleotide polymorphisms (SNPs) located in amelogenesis-related genes (rs3796704 in the ENAM gene, rs546778141 in the AMBN gene, rs2106416 in the AMELX gene, rs7660807 and rs35286445 in the AMTN gene, rs4870723 in the COL14A1 gene, rs2245803 in the MMP20 gene, and rs3828054 in the TUFT1 gene). Data on clinical signs of MIH were collected in accordance with the recommendation and on the proposed MIH clinical data recording sheet [1], and with appropriate preliminary training and calibration. Data on HLA DQ2 and DQ8 haplotypes and on SNPs of amelogenesis-related genes were obtained using DNA isolated from blood samples taken from subjects. The HLA DQ2 and DQ8 alleles were determined using the EliGene® Coeliac RT Kits (90,048-RT; Elisabeth Pharmacon spol. s.r.o., Brno-Zidenice, Czech Republic) on a 7500 Fast RT-PCR System (Applied Biosystems, Waltham, MA, USA). The distributions of SNPs in the amelogenesis-related genes were determined using high resolution melting (HRM) using the Type-IT HRM Master Mix (Qiagen), TaqMan genotyping assays (ID: C__25766207_10; Thermo Fisher Scientific, Waltham, MA, USA) with the TaqMan Universal Master Mix II, or Sanger sequencing using sequencing master mix BigDye® Terminator v3.1 (Applied Biosystems) and ABI 3500 Genetic Analyser (Applied Biosystems). L. Hocevar, J. Kovac, K. Trebusak Podkrajsek, S. Battelino, A. Pavlic, 2020. The possible influence of genetic aetiological factors on molar-incisor hypomineralisation, Arch. Oral. Biol. 118, 104848. https://doi.org/10.1016/j.archoralbio.2020.104848.

The possible influence of genetic aetiological factors on molar-incisor hypomineralisation.

OBJECTIVE: The present study searched for evidence of possible associations between some genetic factors that could affect the development of molar-incisor hypomineralisation (MIH). METHODS: In 113 patients who were surgically treated at an Otorhinolaryngology and Cervicofacial Surgery Clinic (ORL) during early childhood, human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes and single nucleotide polymorphisms (SNP) of eight amelogenesis-related genes were searched in genomic DNA. Genotypes were determined by high resolution melting (HRM), TaqMan genotyping assays, and Sanger sequencing. Association between MIH and the HLA DQ2 and DQ8 alleles was tested using a univariate logistic regression. The significance of genetic variants was analysed using the Cochran-Armitage tests for trend and the Fisher exact tests. RESULTS: We identified MIH in 22 (19.5 %) of the 113 children. Among the evaluated genetic variants, SNP rs2245803 in the MMP20 gene in a homozygous form in a recessive model was associated with MIH development (OR, 2.796; 95 %CI, 1.075 - 4.783; p = 0.0496) with the genotype distribution of TT(3), TG(6) or GG(13) in children with MIH and distribution of TT(18), TG(42) or GG(31) in children without MIH. CONCLUSIONS: While the aetiology of MIH remains unclear, our findings suggest that variants of genes associated with amelogenesis may play important roles in susceptibility to MIH.

The effectiveness of completely and incompletely sealed first permanent molars on caries prevention.

Fissure sealants are effective caries preventive measure. However, a dilemma has been expressed more than once, whether incompletely sealed fissures provides sufficient protection against caries. Dental examinations were performed in 88 children, aged 8 and then 4 years later at 12 years. All first permanent molars (FPMs), as diagnosed at the age of 8, were divided into three groups: nonsealed, incompletely and completely sealed. Four years later caries incidence and changes in presence and quality of fissure sealant were analyzed. At the age of 8 and 12 mean DMFT were 0.73 ± 1.24 and 3.48 ± 3.04, respectively. 71.59% of the 8-year-olds and 78.41% of the 12-year-olds had at least one sealed FPM. At the age of 8, 154 FPMs were completely sealed and 42 FPMs were incompletely sealed. Four years later, 81.17%, 71.43% and 69.4% of FPMs were healthy (sound or with noncavitated caries) in the baseline groups completely sealed, incompletely sealed and nonsealed FPMs, respectively. Incompletely sealed fissures were more susceptible to caries development than completely sealed fissures. It is important that incompletely sealed fissures are resealed as soon as possible.

Case report of a molar-root incisor malformation in a patient with an autoimmune lymphoproliferative syndrome.

BACKGROUND: Molar-root incisor malformation (MRIM) is a novel dental phenotype likely related to a patient's past medical history. This case aimed to confirm MRIM by histological and scanning electron microscopy (SEM) examination for the first time in a patient diagnosed with autoimmune lymphoproliferative syndrome (ALPS) and to propose a possible link between ALPS and MRIM that could be attributable to abnormally proliferated bone marrow. CASE PRESENTATION: A 12.5-year-old boy with an extensive medical history, including diagnosis of ALPS, was examined clinically and radiologically to elucidate the reason for pain primarily originating from the area of the lower left permanent first molar tooth (PFM; tooth 36). Dental examination and radiographic survey revealed abnormal pulp cavity morphology of all four PFMs, and these were extracted, resolving the dental pain in the patient. The extracted PFMs were subjected to light microscopy, SEM evaluation and mineral density and elemental composition analyses. Histology of two PFMs revealed the presence of dentin-, bone- and cartilage-like tissues with abundant blood vessels occupying the majority of the pulp chamber. The root canals were obliterated with mineralized structures resembling pulp stones. Two different, highly mineralized abnormal tissues filling the majority of the pulp chamber revealed by SEM and confirming the diagnosis of MRIM displayed a mineral density and elemental composition similar to those of enamel and dentin, respectively. CONCLUSIONS: It appears likely that in addition to the complex medical history during early childhood in the present case, extensive lymphoid infiltrates that are possible in ALPS patients can be regarded as a cofactor in the development of MRIM by exerting considerable pressure on the developing tooth bud and providing cells capable of differentiating into diverse cell types.

Effect of Repeated Antimicrobial Photodynamic Therapy in Treatment of Periodontitis Associated with Fanconi Anemia.

BACKGROUND AND OBJECTIVE: Periodontal disease is one of common oral manifestations in patients with Fanconi anemia (FA). The aim of the study was to evaluate the effect of photodynamic therapy (PDT) on periodontal clinical and microbial parameters in a patient with FA. MATERIALS AND METHODS: For a 16-year-old girl, diagnosed with having FA and periodontal disease, the protocol treatment with duration of 10 months was designed. Every 2 months, thorough oral cavity disinfection was followed by PDT, using photosensitizer phenothiazine chloride activated by a diode laser light. During each visit, periodontal parameters were evaluated: plaque index (PI), gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP), and clinical attachment level. Simultaneously, the presence of Candida albicans and of five periodontal pathogens was evaluated. RESULTS: Clinical results showed improvement in GI, BOP, and PPD during this 10-month period. BOP subsequently reduced from 100% to 79%, 72%, and 60% at 6, 8, and 10 months, respectively. The proportion of sites with PPD of ≥4 mm decreased from 38.7% at the baseline to zero after 10 months. Further, all five bacterial species and C. albicans were reduced significantly. CONCLUSIONS: PDT effectively influences periodontal healing and reduces periodontopathogenic bacteria without damaging the patient's tissues.

Oral health needs of athletes with intellectual disability in Eastern Europe: Poland, Romania and Slovenia.

OBJECTIVES: The aims of this study were to evaluate the oral condition and treatment needs of Special Olympics (SO) athletes from Poland, Romania and Slovenia. METHODS: A cross-sectional study was performed with data collected through standardised oral screening of athletes who participated in the annual SO events held in Poland, Romania and Slovenia, between 2011 and 2012. The data were compiled and transferred to an SPSS data file for analysis using descriptive statistics. RESULTS: A total of 3,545 athletes participated in the study. Among the main findings, the prevalence of untreated decay was 41% in Poland and 61% in Slovenia, whilst 70% of the Romanian athletes had signs of gingival disease and only 3.8% presented molar fissure sealants. In addition, 47% of Polish athletes were in need of urgent treatment. CONCLUSIONS: Analysis of the results obtained following screening showed comparable oral health needs of athletes with intellectual disability among countries. Exploration of the oral health systems of the countries revealed similar significant co-payments and lack of incentive for dentists to treat patients with special needs. The results from Romania, Poland and Slovenia demonstrated the need for a structured system in which a special population is a target for oral-health-related education programmes and system-included preventive, restorative and maintenance interventions.

Combined effect of amoxicillin and sodium fluoride on the structure of developing mouse enamel in vitro.

OBJECTIVE: Excess fluoride intake during tooth development is known to cause dental fluorosis. It has also been suggested that amoxicillin use in early childhood is associated with enamel hypomineralization. The aim was to investigate separate and combined effects of sodium fluoride (NaF) and amoxicillin on enamel formation in vitro. DESIGN: Mandibular molar tooth germs of E18 mouse embryos were cultured for 10 days in a medium containing NaF (10, 12 or 15µM) and/or amoxicillin (0.5, 1, 2 or 3.6mg/mL) or sodium clavulanate (0.07mg/mL) alone or in combination with 0.5mg/mL of amoxicillin. Morphological changes were studied from the whole tooth photographs and histological tissue sections with light microscope. RESULTS: Only with the highest concentrations of NaF or amoxicillin alone the extent of enamel in the first molars measured as the vertical enamel height/crown height ratio was reduced (p<0.01, p<0.001, respectively). At lower concentrations, combination of NaF (12µM) and amoxicillin (2mg/mL) significantly reduced enamel extent compared with the controls (p<0.001). Histologically, the ameloblasts were still columnar but poorly organized and the nascent enamel was often non-homogeneous. Enamel formation was not seen in any second molars exposed to 12µM NaF and 2mg/mL of amoxicillin (or higher concentrations) compared with the presence of enamel in half of the controls (p<0.001). CONCLUSIONS: Amoxicillin and NaF dose dependently affect developing enamel of mouse molars in vitro and the effects are potentiative. The clinical significance of the results remains to be studied.

Oral health of the elderly living in residential homes in Slovenia.

OBJECTIVES: To evaluate oral health status of the elderly, living in eight randomly selected residential homes for senior citizens across the country. BACKGROUND: The percentage of the elderly is growing worldwide. With ageing, risks of various oral diseases, including dental caries and periodontal disease, are growing. METHODS: Altogether 296 elderly people (88 men, 208 women) of average age 79.89 ± 7.4 years were questioned about their medical condition and oral health practice and examined orally. Evaluation of clinical examination was carried out by DMFT, plaque index (Silness and Löe, 1964) and Community Periodontal Index of Treatment Need (CPITN). RESULTS: Of 296 participants, 106 (35.8%) were edentulous, 95 (32.1%) had one to nine teeth and 95 persons (32.1%) had 10 or more teeth. The average number of teeth in an individual was small: 6.76 ± 7.47. The average number of teeth with caries lesions was 3.59 ± 4.70, filled teeth 1.94 ± 3.63 and teeth without caries or fillings 1.19 ± 2.41. The average DMFT value was 30.75. In 69.5% of participants, dental plaque was visible with the naked eye. Of 171 subjects, in whom CPITN index was appraised, 81.9% would need oral hygiene education, 56.7% would need scaling and root planning and 21.6% would need periodontal surgical treatment. CONCLUSIONS: The results of this study indicate poor oral health of the elderly living in residential homes situated in different towns in Slovenia. It is of utmost importance to highlight the necessity of improving oral health care of this population.

Craniofacial characteristics and genotypes of amelogenesis imperfecta patients.

The aims of the study were to identify craniofacial characteristics in patients with the rough hypoplastic amelogenesis imperfecta (AI) phenotype and to evaluate whether craniofacial variables are related to a mutation in either of the two genes associated with AI, enamelin (ENAM) and amelogenin (AMGX). Eight children (five males and three females) with rough hypoplastic AI phenotype, aged 6.5-15 years, from three families and their parents (three males and three females) were examined clinically, radiographically, and genetically. Seventeen variables were measured on lateral cephalometric radiographs in AI affected (n = 11) and AI unaffected (n = 3) members. Craniofacial measurements were statistically analysed using a Student's t-test. In all 14 individuals, mutation analysis of the ENAM and AMGX genes was performed by direct sequencing of the coding region. All AI affected patients had hypoplastic enamel with a rough surface and malocclusions. In the vertical plane, all AI children presented an anterior and/or posterior open bite (OB). Craniofacial analysis confirmed increased vertical relationships, with increased vertical jaw relationships and higher values for gonial angle. In two AI affected families, A and B, the same heterozygous ENAM g.8344delG mutation was confirmed, while in the third family, neither ENAM nor AMGX mutation was found. All patients with rough hypoplastic AI had a moderate to severe malocclusion with increased vertical dimensions regardless of the presence or absence of the ENAM g.8344delG mutation. As an OB requires appropriate timing of therapy, it is important to diagnose these patients as early as possible.

Clinical and microstructural aberrations of enamel of deciduous and permanent teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) causes multiple endocrine deficiencies, oral candidiasis and different forms of ectodermal dystrophy including enamel hypoplasia, documented in permanent teeth. Our purpose was to examine dental aberrations associated with APECED, including possible manifestations in primary teeth. DESIGN: We studied clinically, radiographically, and by scanning electron microscopy (SEM) teeth of children belonging to two APECED families with different mutations in the AIRE gene. RESULTS: In addition to enamel defects in the permanent teeth we observed hypoplastic pits and hypomaturated patches in the deciduous teeth with underlying changes in the prismatic ultrastructure. The enamel of the permanent molars exhibited a layered arrangement with included whirl-like formations. CONCLUSIONS: Our findings confirm that APECED causes enamel defects that are individually but chronologically distributed, and can alter enamel development early enough to affect deciduous teeth.

Clinical and microstructural aberrations of enamel of deciduous and permanent teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) causes multiple endocrine deficiencies, oral candidiasis and different forms of ectodermal dystrophy including enamel hypoplasia, documented in permanent teeth. Our purpose was to examine dental aberrations associated with APECED, including possible manifestations in primary teeth. DESIGN: We studied clinically, radiographically, and by scanning electron microscopy (SEM) teeth of children belonging to two APECED families with different mutations in the AIRE gene. RESULTS: In addition to enamel defects in the permanent teeth we observed hypoplastic pits and hypomaturated patches in the deciduous teeth with underlying changes in the prismatic ultrastructure. The enamel of the permanent molars exhibited a layered arrangement with included whirl-like formations. CONCLUSIONS: Our findings confirm that APECED causes enamel defects that are individually but chronologically distributed, and can alter enamel development early enough to affect deciduous teeth.

Severely hypoplastic amelogenesis imperfecta with taurodontism.

BACKGROUND: The prominent dental feature of a boy was severely hypoplastic enamel in both primary and permanent teeth. CASE REPORT: Many permanent teeth were already infected while emerging in the oral cavity. Panoramic radiograph showed enlarged and elongated pulp chambers (taurodontism) in the permanent first molars. The clinical and radiological diagnosis was either hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (AIHHT) or tricho-dento-osseous syndrome (TDO). Histological examination of the upper right permanent first molar revealed thin lamellar or somewhat thicker amorphous enamel on approximal surface only with no rods or incremental lines visible. Histologically, the Witkop type AIG designated 'enamel agenesis' cannot be excluded. The medical and dental history of the family members, as well as the boy's medical examination, was noncontributing. He had thick, blond, curly hair. The bone structure of the jaws and skull was normal. For genetic analysis, DLX3 gene was sequenced but no mutation was found. CONCLUSIONS: Since the gene defect of TDO has been localized only in the DLX3 gene, the more probable diagnosis was AI.

Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG.

OBJECTIVE: The main clinical manifestations of amelogenesis imperfecta (AI) include alteration in the quality and quantity of enamel. AI is associated with different mutations in four genes: enamelin (ENAM), amelogenin (AMGX), kallikrein (KLK4) and enamelysin (MMP-20). Seven different mutations have been identified in the enamelin gene (ENAM). DESIGN: In this paper, we describe the phenotype and ultrastructure of enamel observed using scanning electron microscopy (SEM) in patients with two autosomal dominant (AD) mutations in the ENAM gene: g.13185-13186insAG and g.8344delG, each in one of two unrelated families. Mutations were confirmed by sequence analysis of PCR amplified products of all 10 exons and exon/intron boundaries of the ENAM gene. RESULTS: Phenotypic diversity was observed in patients with ENAM gene mutations g.13185-13186insAG with consecutive protein alteration designated as p.P422fsX488 within family 1. In the proband, the enamel of his entire dentition was chalky white with only mild local hypoplastic alteration, while the phenotypic appearance of his father's dentition was that of local hypoplastic AI. In patients with the ENAM gene mutation g.8344delG from family 2 with consecutive protein alteration designated as p.N197fsX277, generalised hypoplastic AI was observed. CONCLUSIONS: Ultrastructural enamel changes in the patient with the autosomal dominant ENAM g.13185-13186insAG mutation, described for the first time in this study, were less pronounced compared to ultrastructural changes in patients with the autosomal dominant ENAM mutation 8344delG. Ultrastructural characteristics of the g.13185-13186insAG mutation revealed deformed prisms, an oval shape on the cross-section and wider interprism spaces, while enamel with the ENAM mutation 8344delG was laminated, but prismless.