Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.

Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin-related disorders. We report a patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation. Click https://www.wileyhealthlearning.com/#/online-courses/a6ef1275-8325-4834-89d2-aa18fa31e63f for the corresponding questions to this CME article.

Dental anomalies in primary dentition and their corresponding permanent teeth.

OBJECTIVES: The objectives of this paper are to estimate the prevalence of dental anomalies in primary dentition in a sample of 2- to 5-year-old Brazilian preschool children, determine their distribution, and investigate their occurrence in the succedaneous teeth of the sample compared with a control group of children with no dental anomalies in the primary dentition. MATERIALS AND METHODS: The one-stage sample comprised 1,718 two to five-year-old children with fully erupted primary dentition clinically examined for dental anomalies. All children presenting dental anomalies underwent panoramic radiographs. Descriptive statistics were performed for the studied variables. A control group matched by sex and age was studied to compare the prevalence ratio for dental anomalies in the permanent dentition. RESULTS: The prevalence of dental anomalies in the primary dentition was 1.8 %, with no significant statistical difference between sexes. Double teeth were the most frequently observed. Dental anomalies on the succedaneous permanent teeth were diagnosed in 54.8 % of the children with affected primary dentition. The prevalence ratio (PR) for dental anomalies in the succedaneous permanent teeth was 17.1 (confidence interval (CI) 5.33-54.12) higher compared with the control group, higher in children with bilateral anomalies (PR = 31.2, CI 10.18-94.36). CONCLUSIONS: An association between anomalies of the permanent dentition and the presence of dental anomalies in primary teeth was observed, especially when they occur bilaterally. CLINICAL RELEVANCE: The results in the present study have a clinical relevance in the diagnosis of children with dental anomalies in primary dentition. Early identification of these anomalies can aid the dentist in planning dental treatment at the appropriate time.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Oral Manifestations in Patients with COVID-19: A 6-Month Update.

This is the first update of the previously published living systematic review that summarized evidence on the prevalence of oral signs and symptoms in patients with COVID-19. Hitherto, 183 studies were included, reporting data from 64,876 patients with COVID-19 worldwide. The overall prevalence of taste disorders was 38% (95% CI = 22% to 56%, I2 = 98%). Hypogeusia, dysgeusia, and ageusia were also evaluated by a meta-analysis, and the pooled prevalence was 34% for hypogeusia, 33% for dysgeusia, and 26% for ageusia. Taste disorders were associated with a positive COVID-19 test (odds ratio [OR] = 7.54, 95% CI = 5.24 to 10.86, I2 = 93%, P < 0.00001), showing high certainty of evidence. However, the association between taste disorders and mild/moderate severity of COVID-19 (OR = 1.63, 95% CI = 1.33 to 1.99, I2 = 69%, P < 0.0001) and female patients with COVID-19 (OR = 1.77, 95% CI = 1.26 to 2.48, I2 = 79%, P = 0.001) presented low certainty of evidence. Xerostomia was a new feature of this update, and the pooled data demonstrated a prevalence of 43% (95% CI = 36% to 50%, I2 = 71%) in patients with COVID-19. Regarding oral mucosal lesions, the most common clinical pattern was aphthous like, followed by herpes-like lesions, candidiasis, glossitis/depapillation/geographic tongue, parotitis, and angular cheilitis. Oral lesions were more frequent in the tongue, lips, and palate, presenting miscellaneous clinical aspects that are more likely to represent coinfections. Therefore, the reanalysis of current evidence suggests the triad xerostomia, taste dysfunction, and oral mucosal lesions as common manifestations in patients with COVID-19. However, these outcomes are under discussion, and more studies will be necessary to confirm their association with direct SARS-CoV-2 infection in the oral cavity.

Oral Manifestations in Patients with COVID-19: A Living Systematic Review.

This living systematic review aims to summarize evidence on the prevalence of oral signs and symptoms in patients with COVID-19. The review was reported per the PRISMA checklist, and the literature search was conducted in 6 databases and in gray literature. Studies published in any language mentioning oral symptoms and signs in patients with COVID-19 were included. The risk of bias was assessed by the Joanna Briggs Institute appraisal tools. The certainty of evidence was evaluated through GRADE assessment. After a 2-step selection, 40 studies were included: 33 cross-sectional and 7 case reports. Overall, 10,228 patients (4,288 males, 5,770 females, and 170 unknown) from 19 countries were assessed. Gustatory impairment was the most common oral manifestation, with a prevalence of 45% (95% CI, 34% to 55%; I2 = 99%). The pooled eligible data for different taste disorders were 38% for dysgeusia and 35% for hypogeusia, while ageusia had a prevalence of 24%. Taste disorders were associated with COVID-19 (odds ratio [OR], 12.68; 95% CI, 6.41 to 25.10; I2 = 63%; P < 0.00001), mild/moderate severity (OR, 2.09; 95% CI, 1.25 to 3.49; I2 = 66%; P = 0.005), and female patients (OR, 1.64; 95% CI, 1.23 to 2.17; I2 = 70%; P = 0.0007). Oral mucosal lesions presented multiple clinical aspects, including white and erythematous plaques, irregular ulcers, small blisters, petechiae, and desquamative gingivitis. Tongue, palate, lips, gingiva, and buccal mucosa were affected. In mild cases, oral mucosal lesions developed before or at the same time as the initial respiratory symptoms; however, in those who required medication and hospitalization, the lesions developed approximately 7 to 24 d after onset symptoms. Therefore, taste disorders may be common symptoms in patients with COVID-19 and should be considered in the scope of the disease's onset and progression. Oral mucosal lesions are more likely to present as coinfections and secondary manifestations with multiple clinical aspects (PROSPERO CRD42020184468).

Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families.

The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II (DGI-II) attending the Dental Anomalies Clinic in Brasilia, Brazil. Physical and oral examinations, as well as radiographic and histopathological analyses, were performed on 28 affected and unaffected individuals. Clinical, radiographic and histopathological analyses confirmed the diagnosis of DGI-II in 19 individuals. Pulp stones were observed in ground sections of several teeth in 2 families, suggesting that obliteration of pulp chambers and root canals results from the growth of these nodular structures. Mutational DSPP gene analysis of representative affected family members revealed 7 various non-disease-causing alterations in exons 1-4 within the dentin sialoprotein domain. Further longitudinal studies are necessary to elucidate the progression of pulpal obliteration in the DGI-II patients studied as well as the molecular basis of their disease.

Case report of a rare syndrome associating amelogenesis imperfecta and nephrocalcinosis in a consanguineous family.

A rare syndrome associating amelogenesis imperfecta (AI) with nephrocalcinosis has been reported. The purpose of this study is to characterise the phenotype of a consanguineous family presenting amelogenesis imperfecta, delayed permanent teeth eruption and nephrocalcinosis. Six family members were examined. Ground sections of the case index deciduous teeth and biopsies of enlarged dental follicles were analysed. The patients's parents were first cousins. The case index had yellow discoloration and altered teeth shapes, retention of deciduous teeth, and delayed eruption. Panoramic radiographs revealed multiple enlarged pericoronal follicles in unerupted teeth and generalised intrapulpal calcifications. Renal ultrasound showed the presence of nephrocalcinosis. No other family members presented enamel defects or nephrocalcinosis. Histologically, the enamel appeared hypoplastic, and dental follicles indicated pericoronal hamartoma. The consanguineous marriage suggests an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect behind this syndrome that associates AI, nephrocalcinosis and impaired tooth eruption.

Dental mineralization.

Extracellular matrix components and cell-derived microstructures are implicated in mineralization processes which occur in dental tissues. The respective role(s) of collagenic and non-collagenic matrix components are reviewed: phosphorylated and non-phosphorylated proteins, proteoglycans and phosphpholipids. Space-filling amphiphilic molecules seem to play an important role in the preorganization and oriented deposition of calcium phosphate on structures serving more or less as passive support in dentine as well as in enamel.

Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI.

Scanning electron microscopy and energy-dispersive X-ray analysis of defects in mature rat incisor enamel after thyroparathyroidectomy.

The surface and the structure of the erupted enamel of the continuously growing rat incisor were studied by scanning electron microscopy (SEM) to analyse the effect of thyroparathyroidectomy on enamel formation. Ten male 21-day-old Wistar rats were thyroparathyroidectomized and five sham-operated rats were used as controls. Two months after surgery the rats were perfused with 1% glutaraldehyde and their mandibles dissected. The erupted ends of the incisors were cut off and routinely processed for SEM. An energy-dispersive analysis of X-rays (EDX analysis) was performed for the calcium:iron ratio of the enamel surface defects. Thyroparathyroidectomy induced surface defects and structural abnormalities in the outer layer of the mature erupted enamel. It was established that the surface and structural defects were related. The EDX analysis of the outer enamel showed that the enamel defects were associated with an abnormal elevation of the iron content. The SEM appearance and the EDX analyses indicated that these defects were hypomineralized and rich in iron. The reddish colour of the enamel is due to the high concentrations of iron.

Autosomal-dominant ankyloglossia and tooth number anomalies.

Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic lingual frenulum. It frequently accompanies X-linked cleft palate and is sometimes seen alone due to mutations in the gene encoding the transcription factor TBX22, while knockout of Lgr5 in the mouse results in ankyloglossia. The aim of the present study was to characterize the phenotype and to verify sequence variations in the LGR5 gene in a Brazilian family with ankyloglossia associated with tooth number anomalies. Twelve individuals of three generations were submitted to physical, oral, and radiographic examinations and molecular analysis. Eight had ankyloglossia with various degrees of severity. Six also had hypodontia in the lower incisor region; one had a supernumerary tooth in this region, and another had a supernumerary tooth in the lower premolar region. The characterization of this family determined an autosomal-dominant inheritance and excluded the LGR5 gene mutations as being involved in the pathogenesis of this condition.

SEM study of the development of rat incisor enamel hypoplasia under hypocalcemia induced by thyro-parathyroidectomy.

Several clinical studies have reported the presence of enamel hypoplasia in congenital hypoparathyroidism or hypocalcemia. In previous studies we showed that thyroparathyroidectomy (TPTX) induced perturbations of the ameloblast morphology and secretion, of the rod pattern and of the enamel surface at late secretory stage and beginning of maturation, and limited hypoplasia in the erupted enamel of rat incisor. The aim of the present study was to evaluate by SEM, the extent and evolution of the enamel alterations of thyro-parathyroidectomized rats during the maturation stage. Wistar rats were thyro-parathyroidectomized and sacrificed 57 days later. The incisors were dissected out and processed for SEM. The surface of the incisor was observed from the end of secretion/beginning of maturation to its incisal erupted end. Transverse sections were prepared to study the structural defects and the prism pattern at different stages. The results showed that the surface of the TPTX incisors presented large hypoplastic defects at the end of secretion/beginning of maturation and only small defects in the erupted part. Transverse sections showed that, at the transition from secretion to maturation, the enamel defects extended to the mid-thickness of the tissue. At the incisal end the defects were limited to the outer enamel. As it is difficult to understand how the large apical defects could recover to appear as small hypoplasia at the incisal end, these results raise new questions concerning: (1) the effect of a long term calcium deficiency upon the cellular activity of the ameloblasts, and (2) the capacity of the enamel organ to compensate structural abnormalities.

Development of enamel defects in rat mandibular incisor after thyro-parathyroidectomy.

Previous studies with scanning electron microscopy (SEM) demonstrated the presence of small hypoplastic defects in the incisal third of incisors and deep hypoplasia in the apical third of the incisors after thyro-parathyroidectomy in the rat. These studies provided a morphological description of the defects, but uncertainty remained concerning their development throughout amelogenesis. The aim of the present investigation was to study, with SEM operated in the backscattered mode, the development of the hypoplastic defects, from the beginning of the secretion to the end of the maturation zone of the enamel, in the lower incisor of thyroparathyroidectomized rats. The results of the present study showed that the large and small defects developed are separate entities that do not develop into the other. The distribution of large defects might be linked to a reduction of the eruption rate in these rats. The pathogenesis of these defects needs further investigation.

Effects of thyro-parathyroidectomy and parathyroidectomy upon dentinogenesis: Part I: Light microscopy.

In order to determine the differential effects of the thyroid hormones and the parathyroid hormone upon dentinogenesis in the rat incisor one control group (C) and four groups of surgically treated rats were studied: parathyroid autotransplanted (PTT), thyroidectomized (TX), parathyroidectomized (PTX), and thyro-parathyroidectomized group. One month after surgery the incisors were dissected and the tissues were prepared for light microscopy and morphometric measurements. This study revealed modifications in the TPTX rats as well as in the PTX rats: an enlargement of the predentin, alterations in the predentin appearance and the presence of mineralization defects. These results confirm that the effects observed are probably due to a PTH deficiency and/or hypocalcemia and suggest that their occurrence is associated with a determined stage of dentinogenesis in the rat.

Effects of thyro-parathyroidectomy and parathyroidectomy upon dentinogenesis: Part II: Electron microscopy.

An ultrastructural study was carried out in order to better characterize the findings observed in the first part of our study. The materials and methods are the same as those used in the preceding paper. This study reveals the occurrence of structures which display a symmetrical cross-banded pattern within the predentin and dentin of thyro-parathyroidectomized (TPTX) and parathyroidectomized (PTX) rats. A difference in the distribution of the symmetrical banded structures as dentinogenesis advances, as well as differences in the amount of the symmetrical banded structures between TPTX and PTX rats were observed. The symmetrical banded structures correspond with the so-called symmetrical SLS previously described in the incisor of normal and pathologic rats. The occurrence of these structures at a given stage of the incisor development suggests that the odontoblast is sensitive to the parathyroid hormone deficiency and/or hypocalcemia in a precise stage of its maturation.

Morphological study of amelogenesis in the rat lower incisor after thyro-parathyroidectomy, parathyroidectomy and thyroidectomy.

The effects of thyro-parathyroidectomy, parathyroidectomy or thyroidectomy upon enamel formation in the rat incisor were studied. One control group and four groups of surgically treated rats were used: parathyroid autotransplanted, thyroidectomized, parathyroidectomized, and thyro-parathyroidectomized. One month after surgery, the incisors were processed for light and electron microscopy. The present study revealed perturbations of the Tomes process morphology, of the rod pattern in the inner enamel formation, of the enamel surface, and of the mineralization after thyro-parathyroidectomy. After parathyroidectomy, only mineralization defects could be visualised. No effects were observed in enamel after thyroidectomy. A severe hypocalcemic state as seen in thyro-parathyroidectomized rats affects the enamel shape, and mineralization, and the morphology and function of secretory ameloblasts. Knowledge of the way in which the alteration of the enamel surface is produced should contribute to a better understanding of the development of tooth enamel.