Individualized digitally designed surgical template for guided soft tissue surgery in cases with severe gingival enlargement: A clinical application in hereditary gingival fibromatosis.

AIM: The purpose of this study was to present the use of computer-assisted periodontal surgery utilizing a novel surgical guide for cases with severe gingival enlargement through a clinical application in a patient with hereditary gingival fibromatosis. MATERIALS AND METHODS: The treatment plan included nonsurgical periodontal therapy, surgical periodontal treatment, and regular periodontal maintenance before the initiation of orthodontic treatment. Due to the increased soft tissue thickness, a surgical guide with a novel design was fabricated to facilitate the periodontal surgery since most of the patient's teeth were malpositioned and underexposed due to fibromatosis. For this purpose, the patient's intraoral scan was merged with a CBCT image in order to plan surgical excisions based on the anatomy of the teeth and the bone contour. RESULTS: The customized surgical guide facilitated the gingivectomy by controlling not only the shape of the initial incisions but also their orientation toward the level of the cementoenamel junction, improving the efficiency of the clinical time compared with freehand surgery and assisting in the verification of the final soft tissue shape, based on the treatment plan. CONCLUSION: Digital technology through the superimposition of multiple data sets can assist in the diagnosis and multidisciplinary management of cases with gingival fibromatosis. The proposed design of the surgical guide can facilitate soft tissue surgery based on the digital treatment plan, leading to more predictable management of the soft tissue, especially in patients with severe gingival enlargement, as in cases with hereditary gingival fibromatosis or drug-induced gingival overgrowth.

Loss of TBC1D2B causes a progressive neurological disorder with gingival overgrowth.

Biallelic loss-of-function variants in TBC1D2B have been reported in five subjects with cognitive impairment and seizures with or without gingival overgrowth. TBC1D2B belongs to the family of Tre2-Bub2-Cdc16 (TBC)-domain containing RAB-specific GTPase activating proteins (TBC/RABGAPs). Here, we report five new subjects with biallelic TBC1D2B variants, including two siblings, and delineate the molecular and clinical features in the ten subjects known to date. One of the newly reported subjects was compound heterozygous for the TBC1D2B variants c.2584C>T; p.(Arg862Cys) and c.2758C>T; p.(Arg920*). In subject-derived fibroblasts, TBC1D2B mRNA level was similar to control cells, while the TBC1D2B protein amount was reduced by about half. In one of two siblings with a novel c.360+1G>T splice site variant, TBC1D2B transcript analysis revealed aberrantly spliced mRNAs and a drastically reduced TBC1D2B mRNA level in leukocytes. The molecular spectrum included 12 different TBC1D2B variants: seven nonsense, three frameshifts, one splice site, and one missense variant. Out of ten subjects, three had fibrous dysplasia of the mandible, two of which were diagnosed as cherubism. Most subjects developed gingival overgrowth. Half of the subjects had developmental delay. Seizures occurred in 80% of the subjects. Six subjects showed a progressive disease with mental deterioration. Brain imaging revealed cerebral and/or cerebellar atrophy with or without lateral ventricle dilatation. The TBC1D2B disorder is a progressive neurological disease with gingival overgrowth and abnormal mandible morphology. As TBC1D2B has been shown to positively regulate autophagy, defects in autophagy and the endolysosomal system could be associated with neuronal dysfunction and the neurodegenerative disease in the affected individuals.

A recurrent KCNK4 variant in a dominant pedigree with hypertrichosis and gingival fibromatosis syndrome: Variable phenotypic expressivity and insights on patients' dental management.

Abnormal hyperpolarization of the KCNK4 gene, expressed in the nervous system, brain, and periodontal ligament fibroblasts, leads to impaired neurotransmitter sensitivity, cardiac arrhythmias, and endocrine dysfunction, as well as, progressive cell proliferation. De novo gain of function variants in the KCNK4 gene were reported to cause a recognizable syndrome characterized by facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG, OMIM# 618381). FHEIG is extremely rare with only three reported cases in the literature. Herein, we describe the first inherited KCNK4 variant (c.730G>C, p.Ala244Pro) in an Egyptian boy and his mother. Variable phenotypic expressivity was noted as the patient presented with the full-blown picture of the syndrome while the mother presented only with hypertrichosis and gingival overgrowth without any neurological manifestations. The c.730G>C (p.Ala244Pro) variant was described before in a single patient and when comparing the phenotype with our patient, a phenotype-genotype correlation seems likely. Atrial fibrillation and joint laxity are new associated findings noted in our patient extending the clinical phenotype of the syndrome. Dental management was offered to the affected boy and a dramatic improvement was noted as the patient regained his smile, restored the mastication function, and resumed his psychological stability.

Gingivectomy with Diode Laser Versus the Conventional Scalpel Surgery and Nonsurgical Periodontal Therapy in Treatment of Orthodontic Treatment-Induced Gingival Enlargement: A Systematic Review.

Background and objective: Some studies support the superiority of diode laser gingivectomy to scalpel surgery and nonsurgical treatments. However, a systematic review on this topic is lacking. This study aimed to compare gingivectomy with diode laser versus the conventional scalpel surgery and nonsurgical periodontal therapy (NSPT) in the treatment of orthodontic treatment-induced gingival enlargement (GE). Materials and methods: In this systematic review, an electronic search of the relevant literature was conducted in Web of Science, Medline/PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ProQuest with no language restriction. Randomized clinical trials published between 1985 and 2020 on comparative treatment of orthodontic treatment-induced GE by diode laser gingivectomy and scalpel surgery or NSPT regarding intraoperative and postoperative bleeding and/or pain were included. Risk of bias was assessed by the Cochrane 1 tool. Results: Of the initially retrieved 288 articles, 40 were duplicates and excluded; 236 articles were excluded following title and abstract screening, and 5 others were excluded following full-text assessment. Finally, 7 studies underwent systematic review. In the risk-of-bias assessment, 5 studies scored 2, and 2 studies scored 3 out of 6. Intraoperative and postoperative bleeding and pain were found to be significantly lower in the laser group. Conclusions: Within the limitations of this systematic review and with respect to the quality of evidence, the present results revealed lower level of pain and bleeding in diode laser gingivectomy compared with the conventional scalpel surgery and NSPT for treatment of orthodontic treatment-induced GE.

Detection of tooth numbering, frenulum attachment, gingival overgrowth, and gingival inflammation signs on dental photographs using convolutional neural network algorithms: a retrospective study.

OBJECTIVES: This study aimed to develop an artificial intelligence (AI) model that can determine automatic tooth numbering, frenulum attachments, gingival overgrowth areas, and gingival inflammation signs on intraoral photographs and to evaluate the performance of this model. METHOD AND MATERIALS: A total of 654 intraoral photographs were used in the study (n = 654). All photographs were reviewed by three periodontists, and all teeth, frenulum attachment, gingival overgrowth areas, and gingival inflammation signs on photographs were labeled using the segmentation method in a web-based labeling software. In addition, tooth numbering was carried out according to the FDI system. An AI model was developed with the help of YOLOv5x architecture with labels of 16,795 teeth, 2,493 frenulum attachments, 1,211 gingival overgrowth areas, and 2,956 gingival inflammation signs. The confusion matrix system and ROC (receiver operator characteristic) analysis were used to statistically evaluate the success of the developed model. RESULTS: The sensitivity, precision, F1 score, and AUC (area under the curve) for tooth numbering were 0.990, 0.784, 0.875, and 0.989; for frenulum attachment these were 0.894, 0.775, 0.830, and 0.827; for gingival overgrowth area these were 0.757, 0.675, 0.714, and 0.774; and for gingival inflammation sign 0.737, 0.823, 0.777, and 0.802, respectively. CONCLUSION: The results of the present study show that AI systems can be successfully used to interpret intraoral photographs. These systems have the potential to accelerate the digital transformation in the clinical and academic functioning of dentistry with the automatic determination of anatomical structures and dental conditions from intraoral photographs.

Drug-Induced Gingival Overgrowth-Molecular Aspects of Drug Actions.

Drug-induced gingival overgrowth (DIGO) is one of the side effects produced by therapeutic agents, most commonly phenytoin, nifedipine and cyclosporin A. However, the precise mechanism of DIGO is not entirely understood. A literature search of the MEDLINE/PubMed databases was conducted to identify the mechanisms involved in DIGO. The available information suggests that the pathogenesis of DIGO is multifactorial, but common pathogenic sequelae of events emerge, i.e., sodium and calcium channel antagonism or disturbed intracellular handling of calcium, which finally lead to reductions in intracellular folic acid levels. Disturbed cellular functions, mainly in keratinocytes and fibroblasts, result in increased collagen and glycosaminoglycans accumulation in the extracellular matrix. Dysregulation of collagenase activity, as well as integrins and membrane receptors, are key mechanisms of reduced degradation or excessive synthesis of connective tissue components. This manuscript describes the cellular and molecular factors involved in the epithelial-mesenchymal transition and extracellular matrix remodeling triggered by agents producing DIGO.

Cyclosporine A-induced gingival overgrowth in renal transplant patients accompanied by epithelial-to-mesenchymal transition.

OBJECTIVE: To investigate the association between the prevalence of cyclosporin A-induced gingival overgrowth and the expression of the epithelial-to-mesenchymal transition factors in the gingival tissues of renal transplant patients. BACKGROUND: Gingival overgrowth (GO) is a frequent complication in organ transplant patients treated with the immunosuppressant cyclosporin A (CsA). The epithelial-to-mesenchymal transition (EMT) is considered a factor contributing to CsA-induced GO. However, current knowledge on this topic is sparse. METHODS: Sixty-three renal transplant patients were divided into two groups according to the occurrence of GO: those with gingival overgrowth (GO+ group) and those without gingival overgrowth (GO- group). Data on age, sex, and use of immunosuppressant and calcium channel blocker medications, serum creatinine values, peak concentrations of blood CsA, and gingival hyperplasia scores were recorded to identify clinically pathogenic factors. Gingival tissues from five patients with CsA-induced GO and five healthy subjects were selected for histomorphological observation with hematoxylin-eosin staining, Masson staining, and immunohistochemical staining. The mRNA expression of EMT factors was detected with reverse transcription-quantitative PCR. RESULTS: The use of CsA significantly increased the prevalence of GO in renal transplant patients. The expression of α-SMA, SMAD4, and TGM2 was upregulated and that of E-cadherin was downregulated in the gingival tissues of patients with CsA-induced GO compared with those of the corresponding controls. CONCLUSION: Treatment with CsA is closely related to the occurrence of GO in renal transplant patients and EMT plays an important role in CsA-induced gingival tissue hyperplasia.

Enhancement of receptor-mediated calcium responses by phenytoin through the suppression of calcium excretion in human gingival fibroblasts.

BACKGROUND AND OBJECTIVES: Gingival overgrowth caused by phenytoin is proposed to be associated with Ca2+ signaling; however, the mechanisms that increase the intracellular Ca2+ concentration ([Ca2+ ]i ) are controversial. The current study aimed to elucidate the mechanism underlying the phenytoin-induced increase in [Ca2+ ]i in human gingival fibroblasts (HGFs). METHODS: Effects of 100 µM phenytoin on [Ca2+ ]i in HGFs were examined at the single-cell level using fluorescence images of fura-2 captured by an imaging system consisting of an EM-CCD camera coupled to an inverted fluorescence microscope at room temperature. RESULTS: Exposure of HGFs to 100 µM phenytoin induced a transient increase in [Ca2+ ]i in the absence of extracellular Ca2+ , indicating that the phenytoin-induced increase in [Ca2+ ]i does not require an influx of extracellular Ca2+ . In addition, phenytoin increased [Ca2+ ]i in HGFs depleted of intracellular Ca2+ stores by thapsigargin, indicating that neither Ca2+ release from stores nor inhibition of Ca2+ uptake is involved. Furthermore, the phenytoin-induced [Ca2+ ]i elevation was reduced to 18.8% in the absence of extracellular Na+ , and [Ca2+ ]i elevation upon removal of extracellular Na+ was reduced to 25.9% in the presence of phenytoin. These results imply that phenytoin increases [Ca2+ ]i of HGFs by suppressing the Na+ /Ca2+ exchanger. Suppression of intracellular Ca2+ excretion is thought to enhance the Ca2+ responses induced by various stimuli. Analysis at the single-cell level showed that stimulation with 1 µM ATP or 3 µM histamine increased [Ca2+ ]i in 20-50% of cells, and [Ca2+ ]i increased in many unresponsive cells in the presence of phenytoin. CONCLUSION: Our findings demonstrate that phenytoin induced increase in [Ca2+ ]i by the inhibition of Ca2+ efflux in HGFs. It was also found that phenytoin strongly enhanced small Ca2+ responses induced by stimulation with a low concentration of ATP or histamine by inhibiting Ca2+ efflux. These findings suggest a possibility that phenytoin causes drug-induced gingival overgrowth by interacting with inflammatory bioactive substances in the gingiva.

The PTEN hamartoma tumor syndrome: how oral clinicians may save lives.

INTRODUCTION: Patients with the PTEN hamartoma tumor syndrome (PHTS) have an 81%-90% cumulative lifetime risk of developing cancer. Around 90% of these patients have recognizable oral features. Receiving a diagnosis may save these patients' lives. This is the first presentation of a family with the PHTS diagnosis with focus on the oral and periodontal findings and treatments. CASE PRESENTATION: All three children (one son and two daughters) inherited the same heterozygous variant in the PTEN gene from their father. Gingival overgrowth was observed in all patients in addition to macrocephaly. Other findings included fissured tongue, high arched palate, papules, and trichilemmomas. The father had experienced severe tooth loss. Surgery was performed to treat the gingival overgrowth and periodontal pockets; however, the treatment was characterized by multiple recurrences of the overgrowth. CONCLUSIONS: Oral changes, macrocephaly, tumors, and/or a family history of benign or malignant lesions are important features that oral clinicians should be aware of for a possible PHTS diagnosis. Patients suspected of having PHTS should be referred to a medical practitioner, specifically a geneticist, for further diagnostic investigations. The periodontal problems seemed to be difficult to control for these patients. They will likely need an active and frequent maintenance therapy to control the persistent inflammation and gingival overgrowth. In addition, they need a thorough monitoring for benign or malignant changes in the orofacial regions. Why are these cases new information? Oral features are found in 90% of the cases with the PHTS diagnosis. The periodontal findings showed a persistent recurrence of gingival overgrowth with a strong probability of serious periodontal diseases. What are the keys to successful management of these cases? A suspicion of a PHTS diagnosis with a referral to a medical practitioner, specifically a geneticist, for complete workup may help save these patients' lives. Close monitoring during maintenance therapy with re-treatment as needed to prevent further periodontal complications. Continued monitoring and treatment throughout the patient's lifetime for development of recurrent or new, benign or malignant lesions at relevant sites. What are the primary limitations to success in these cases? A failure to identify the PHTS syndrome with the accompanying oral and periodontal complications. Complications may lead to a delay in appropriate treatment. Inability to control the persistent gingival overgrowth and a deteriorating periodontal condition. A failure to discover benign and malignant lesions in the orofacial region.

Wound healing effect of a one-week Aloe Vera mouthwash: a pilot study / Efeito de reparação tecidual de uma semana de enxaguante bucal de Aloe Vera: um estudo piloto

Aloe Vera, a perennial Liliaceae plant, has medical, cosmetic, and wound-healing properties. Aloe vera has antioxidant, anti-cancer, anti-diabetic, and regenerative effects. Glucommannan increases collagen synthesis and aids healing after ginivectomy treatment. Natural mouthwashes may offer gingival wound healing efficacy with reduced side-effects when compared to Chlorhexidine. Objective: the objective of this clinical study was to compare the effects on wound healing of a one-week Aloe vera mouthwash with chlorhexidine mouthwash before gingivectomy surgical therapy. Material and Methods:a total of 45 individuals experiencing inflammatory gingival enlargement were included in the study. They underwent professional mechanical plaque removal and were then randomly divided into three groups. In group I, comprising 15 patients, participants were advised to utilize 100% Aloe vera juice as a mouthwash twice daily. Group II, also consisting of 15 patients, was instructed to use Chlorhexidine (0.2%) mouthwash twice daily. The Control group, which consisted of 15 patients, was recommended to use a placebo mouth rinse in addition to mechanical plaque removal. During the second visit, which occurred one week after the initial visit, the enlarged gingival tissue was surgically removed through scalpel gingivectomy. Immunohistochemical (IHC) analysis was performed on the excised tissue to measure the l evels of fibroblast growth factor-2. Results: when compared to the control group, Aloe vera showed significant differences regarding the expression of fibroblast growth factor-2(FGF-2), and highly significant differences in angiogenesis. At the same time, there were substantial differences in angiogenesis w ith no significant differences in the expression of FGF2 between Chlorhexidine and control groups. Conclusion: aloe vera has exhibited potential wound-healing effects as i t s ignificantly affected the IHC expression of FGF2 and angiogenesis when used as an adjunct to plaque control before gingivectomy surgical therapy (AU)

Aloe Vera, uma planta perene de Liliaceae, tem propriedades médicas, cosméticas e cicatrizantes. Aloe vera tem efeitos antioxidantes, anticancerígenos, antidiabéticos e regenerativos. O glucomanano aumenta a síntese de colágeno e auxilia na cicatrização a pós o tratamento de gengivectomia. Enxaguatórios bucais naturais podem oferecer efi cácia na reparação de feridas gengivais com efeitos colaterais reduzidos quando comparados à clorexidina. Objetivo:O objetivo deste estudo clínico foi comparar os efeitos na cicatrização de feridas de uma semana de enxaguatório bucal de Aloe vera com clorexidina antes da terapia cirúrgica de gengivectomia. Material e Métodos: um total de 45 indivíduos com aumento gengival inflamatório foram incluídos no estudo. Eles foram submetidos à remoção mecânica profissional da placa e foramdivididos aleatoriamente em três grupos. No grupo I, composto por 15 pacientes, os participantes foram orientados a utilizar 100% de suco de Aloe vera como enxaguante bucal duas vezes ao dia. O grupo II, também composto por 15 pacientes, foi instruído a usar enxaguante bucal com clorexidina (0,2%) duas vezes ao dia. O grupo controle, composto por 15 pacientes, foi recomendado o uso de enxaguatório bucal placebo além da remoção mecânica da placa. Durante a segunda visita, que ocorreu uma semana após a visita inicial, o tecido gengival aumentado foi removido cirurgicamente por meio de gengivectomia com bisturi. A análise imuno-histoquímica (IHC) foi realizada no tecido excisado para medir os níveis do fator de crescimento de fibroblastos-2 (FGF-2). Resultados: quando comparado ao grupo controle, o Aloe vera apresentou diferenças significativas em relação àexpressão do FGF-2, e diferenças altamente significativas na angiogênese. Ao mesmo tempo, houve diferenças substanciais na angiogênese, sem diferenças significativas na expressão de FGF-2 entre a clorexidina e os grupos controle. Conclusão: Aloe vera exibiu potenciais efeitos de cicatrização de feridas, pois afetou significativamente a expressão IHC de FGF-2 e a angiogênese quando usada como adjuvante no controle de placa antes da terapia cirúrgica de gengivectomia (AU)

Biological Roles of Fibroblasts in Periodontal Diseases.

Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many inflammatory cytokines secreted by immune or tissue cells, such as interleukin-6. In contrast, gingival overgrowth develops as a side effect of specific drugs, such as immunosuppressants, anticonvulsants, and calcium channel blockers. Human gingival fibroblasts (HGFs) are the most abundant cells in gingival connective tissue, and human periodontal ligament fibroblasts (HPLFs) are located between the teeth and alveolar bone. HGFs and HPLFs are both crucial for the remodeling and homeostasis of periodontal tissue, and their roles in the pathogenesis of periodontal diseases have been examined for 25 years. Various responses by HGFs or HPLFs contribute to the progression of periodontal diseases. This review summarizes the biological effects of HGFs and HPLFs on the pathogenesis of periodontal diseases.

Phenytoin induces connective tissue growth factor (CTGF/CCN2) production through NADPH oxidase 4-mediated latent TGFß1 activation in human gingiva fibroblasts: Suppression by curcumin.

OBJECTIVE AND BACKGROUND: Gingival overgrowth (GO) is a common side effect of some drugs such as anticonvulsants, immunosuppressant, and calcium channel blockers. Among them, the antiepileptic agent phenytoin is the most common agent related to this condition due to its high incidence. Transforming growth factor ß (TGFß) importantly contributes to the pathogenesis of GO. Connective tissue growth factor (CTGF or CCN2) is a key mediator of tissue fibrosis and is positively associated with the degree of fibrosis in GO. We previously showed that Src, c-jun N-terminal kinase, and Smad3 mediate TGFß1-induced CCN2 protein expression in human gingival fibroblasts (HGFs). This study investigates whether phenytoin can induce CCN2 synthesis through activated latent TGFß in HGFs and its mechanisms. METHODS: CCN2 synthesis, latent TGFß1 activation, and cellular reactive oxygen species (ROS) generation in HGFs were studied using western blot analysis, a TGFß1 Emax® ImmunoAssay System, and 2',7'-dichlorodihydrofluorescein diacetate (an oxidation-sensitive fluorescent probe), respectively. RESULTS: Phenytoin significantly stimulated CCN2 synthesis, latent TGFß1 activation, and ROS generation in HGFs. Addition of an TGFß-neutralizing antibody, TGFß receptor kinase inhibitor SB431542, and Smad3 inhibitor SIS3 completely inhibited phenytoin-induced CCN2 synthesis. General antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor diphenylene iodonium, and specific NOX4 inhibitor plumbagin almost completely suppressed phenytoin-induced total cellular ROS and latent TGFß1 activation. Curcumin dose-dependently decreased phenytoin-induced TGFß1 activation and CCN2 synthesis in HGFs. CONCLUSIONS: Our findings indicated that NOX4-derived ROS play pivotal roles in phenytoin-induced latent TGFß1 activation. Molecular targeting the phenytoin/NOX4/ROS/TGFß1 pathway may provide promising strategies for the prevention and treatment of GO. Curcumin-inhibited phenytoin-induced CCN2 synthesis is caused by the suppression of latent TGFß1 activation.

Cyclosporine-induced gingival overgrowth-Review.

Drug-induced gingival overgrowth (DIGO) is an undesirable effect resulting from the therapy of one of the three groups of drugs: phenytoin, calcium channel blockers, and cyclosporine A (CsA). It is caused by a fibrous overgrowth leading to gingivitis, periodontitis, and even tooth loss. Possible consequences include tooth decay worsening, pain and difficulty in eating, bleeding gums, and bad breath. The pathomechanism of the hypertrophy is unknown, but there is a correlation between insufficient oral hygiene and the severity of this phenomenon. The gender and age predilection of gingival hyperplasia as a result of CsA therapy is also noticeable. It is most common in children and adolescents of the male sex. The beneficial effect of the removal of tartar and local irritants in reducing the above symptoms has been demonstrated. One of the treatments for DIGO is conventional gingivectomy. The paper is a review article about cyclosporine-induced gingival hyperplasia.

Role of histopathology in the management of the gingival enlargement in a patient on antihypertensive therapy based on calcium channel blockers: a case report.

Periodontal pathology is often represented by increases in gingival volume, with pronounced inflammatory phenomena. These manifestations require a more accurate diagnosis and knowledge of the etiopathogenic factors involved. The periodontal treatment applied must be related with the etiopathogenic circumstances. Periodontal disease sometimes has a complex appearance, with intertwined local and systemic favorable factors that make it difficult to include it in a certain taxonomic form. Also, in general, the adult patients have associated chronic diseases that involve the administration of several drugs, which induce on long-term both therapeutic and side effects. Furthermore, diseases in the oral cavity may occur frequently, which require complex and associated dental and periodontal treatment, also occlusal rebalancing, which is a real interdisciplinary challenge. In this case report, periodontal status is determined by a combination of local and systemic favorable factors. However, the histopathological analysis of the gingival samples revealed inflammation without characteristic fibrous hyperplasia changes of the Amlodipine calcium channel blocker (CCB) administration, the antihypertensive medication of the patient. Thus, Amlodipine does not have a hyperplasic effect on gingival mucosa in all cases. Therefore, even if they are more expensive, investigations must be complex, if necessary, in establishing the involvement of the side effect of the systemic medication in periodontal pathological changes. CCB systemic medication is essential, even vital, for maintain the arterial pressure at normal values, should not be altered without the real indication and to the recommendation from a specialist doctor, and the periodontal treatment must be focused to eliminate the local factors.

Bibliometric analysis of research trends and characteristics of drug-induced gingival overgrowth.

Objectives: Drug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to the category of immunosuppressants, anticonvulsants, and calcium channel blockers, respectively. This bibliometric analysis aims to depict the main citation characteristics and analyze the research trends in DIGO investigations. Methods: An exhaustive search was performed in the Scopus database to create the bibliometric list of DIGO in the syntax. Furthermore, the information related to the number of citations, drugs related to DIGO, study topic and design, authorship, publication year, journal, contributing institution, country of origin, and the department was extracted. Results: In total, 399 papers on DIGO were retrieved in this study. The total number of citations and that after the removal of self-citations were 7,814 and 7,314, respectively. The mean number of citations was 19.6 in a range of 0-608. The main paper types were articles (76.94%) and reviews (19.55%). A remarkable increasing trend in the number of citations has been observed since 1994. Cyclosporine (44.89%) is the most commonly used drug that shares a close relationship with DIGO, followed by phenytoin (18.22%), nifedipine (17.93%), and amlodipine (6.81%). The review (27.82%) type constituted the most widely used design in the DIGO studies. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been prominent topics of research works for several years. Conclusions: This bibliometric analysis will facilitate the understanding of researchers and clinicians, especially those at the beginning of their careers in periodontology on DIGO, by identifying landmark research and providing an overview of this field.

Colágeno tipo I en el agrandamiento gingival inducido por tratamiento ortodóntico: un estudio inmunohistoquímico piloto / Type I Collagen in Gingival Overgrowth Induced by Orthodontic Treatment: A Pilot Immunohistochemical Study / Colágeno do tipo I no aumento gengival induzido por tratamento ortodôntico: um estudo imuno-histoquímico piloto

el tratamiento ortodóntico es responsable del agrandamiento gingival (ag), una condición clínica caracterizada por el crecimiento patológico, difuso o localizado del tejido gingival. La acumulación excesiva de la matriz extracelular (mec), incluyendo el colágeno tipo I, parece contribuir a las manifestaciones patológicas del ag. El objetivo del artículo es identificar y describir la distribución del colágeno tipo I en el tejido gingival de pacientes con ag por ortodoncia fija. Materiales y métodos: estudio de tipo descriptivo que analizó los tejidos gingivales de sujetos diagnosticados con ag portadores de ortodoncia (test, n = 5) e individuos periodontalmente sanos (control, n = 5). Las muestras se obtuvieron mediante gingivectomía. Todas las biopsias fueron fijadas, incluidas en parafina, cortadas y analizadas por medio de la coloración rojo picrosirius/verde rápido, con el propósito de distinguir las fibras de colágeno. Mediante una reacción inmunohistoquímica, el colágeno tipo I fue identificado con anticuerpo monoclonal. Resultados: en los pacientes con ag por tratamiento ortodóntico, se identificó un tejido epitelial hiperplásico con aumento evidente de las prolongaciones epiteliales y un tejido conectivo con abundantes haces de fibras de colágenos, principalmente en la lámina basal y la zona subyacente. Las fibras de colágeno tipo I en los tejidos de pacientes con ag por ortodoncia fueron gruesas de aspecto desorganizado, con una tinción inmunohistoquímica intensa, en comparación con las fibras del grupo control. Conclusiones: el aumento de fibras de colágenos, en especial de colágeno de tipo I, es un hallazgo histológico que caracteriza a los pacientes con ag por ortodoncia fija.

Orthodontic treatment is responsible for gingival overgrowth (go), a clinical condition charac-terized by pathological, diffuse, or localized growth of gingival tissue. Excessive accumulation of the extra-cellular matrix, including type I collagen, contributes to the pathological manifestations of go. The objective of this study is to identify and describe the distribution of type I collagen in the gingival tissue of patients with go because of fixed orthodontics. Materials and Methods: A descriptive study that analyzed the gingival tissues of subjects diagnosed with go with orthodontic (test, n = 5) and periodontally healthy individuals (control, n = 5). The samples were obtained by gingivectomy. All the biopsies were fixed, embedded in paraf-fin, and cut and analyzed using picrosirius red/fast green staining, in order to distinguish the collagen fiber. By means of an immunohistochemical reaction, type I collagen was identified with a monoclonal antibody. Results: A hyperplastic epithelial tissue was identified with an evident increase in epithelial processes and connective tissue with abundant bundles of collagen fiber, mainly in the basal lamina and the underlying area in patients with go because of orthodontic treatment. Type I collagen fiber in the tissues of patients with orthodontic go were thick and disorganized in appearance with intense immunohistochemical stain-ing, compared to the fibers of the control group. Conclusions:The increase in collagen fibers, particularly type I collagen, is a histological finding that characterizes patients with go because of fixed orthodontics.

• tratamento ortodôntico é responsável pelo aumento gengival (ag), uma condição clínica caracterizada pelo crescimento patológico difuso ou localizado do tecido gengival. O acúmulo excessivo de matriz extracelular (mec), incluindo colágeno tipo I, parece contribuir para as manifestações patoló-gicas do ag. O objetivo deste trabalho é identificar e descrever a distribuição do colágeno do tipo I no tecido gengival de pacientes com AG devido à ortodontia fixa. Materiais e métodos: estudo descritivo que analisou os tecidos gengivais de indivíduos diagnosticados com ag em uso de ortodontia (teste, n = 5) e indivíduos periodontalmente saudáveis (controle, n = 5). As amostras foram obtidas por gengivectomia. Todas as biópsias foram fixadas, embebidas em parafina, cortadas e analisadas com coloração picrosirius vermelho/verde rápido, a fim de distinguir as fibras colágenas. Usando uma reação imuno-histoquímica, o colágeno tipo I foi identificado com anticorpo monoclonal. Resultados: em pacientes com ag devido ao tratamento ortodôntico, foi identificado tecido epitelial hiperplásico com evidente aumento das exten-sões epiteliais e tecido conjuntivo com abundantes feixes de fibras colágenas, principalmente na lâmina basal e região subjacente. As fibras de colágeno tipo I em tecidos de pacientes com ag ortodôntico eram espessas com aspecto desorganizado e intensa coloração imuno-histoquímica, em comparação com as fibras do grupo controle. Conclusões: o aumento das fibras colágenas, principalmente do colágeno do tipo I, é um achado histológico que caracteriza os pacientes com ag devido à ortodontia fixa.

Biallelic frameshift variant in the TBC1D2B gene in two siblings with progressive gingival overgrowth, fibrous dysplasia of face, and mental deterioration.

Biallelic loss-of-function variants in the TBC1D2B gene were recently reported as a cause of a neurodevelopmental disorder with seizures and gingival overgrowth. Here, we report two male siblings with the similar clinical characteristics. They started with gingival overgrowth and bilateral growth of soft tissues in the malar region at 3 years of age, which evolved with significant maxillary hypertrophy and compression of the brainstem due to fibrous dysplasia of facial bones. After disease evolution, they presented with mental deterioration, limb tremors, and gait ataxia. One of them also presented with seizures. Whole exome sequencing revealed a novel biallelic frameshift variant [c.595del; p.(Val199Trpfs*22)] in the TBC1D2B gene in both patients, which was confirmed and found in heterozygous state in each of their parents. There are strong similarities in clinical characteristics, age of onset, and evolution between the patients described here and cases reported in the literature, including cherubism-like phenotype with progressive gingival overgrowth and seizures. This is the fourth family in the world in which a biallelic loss-of-function variant in the TBC1D2B gene is associated with this phenotype. These results support that loss of TBC1D2B is the cause of this rare condition.