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.

Periodontal complications of prescription and recreational drugs.

Drug use for both therapeutic and recreational purposes is very widespread in most societies. The range of drugs used, the variations in response to these drugs and other health and behavioral confounders mean that drug use may be an important contributor to individualized periodontal diagnoses. In this narrative review, we review the main reported effects of drugs on the periodontal tissues and periodontal disease processes. Although some of the more common adverse drug reactions on periodontal tissues are well described, in many other cases the evidence for these drug effects is quite limited and based on small case series or isolated reports. Prescription drugs are responsible for a range of effects, including drug-induced gingival overgrowth and increased gingival bleeding, and influence periodontal inflammation and periodontal breakdown. The effects of recreational drugs on the periodontal tissues is less well researched, perhaps for the obvious reason that assembling large cohorts of recreational drug users presents particular challenges. Use of nearly all of these substances is associated with poorer periodontal and dental health, although there is almost certainly a large degree of behavioral confounding in these findings. Overall, further studies of adverse drug reactions on the periodontal tissues are required as this continues to be an important and increasing factor in periodontal health determination.

Microarray and quantitative RT-PCR analyses in calcium-channel blockers induced gingival overgrowth tissues of periodontitis patients.

OBJECTIVES: The purpose of the present study was to analyse transcriptomes and mRNA expression levels for specific genes in calcium-channel blocker-induced gingival overgrowth (GO) tissues. DESIGN: Eight gingival tissues samples (from both GO negative and positive sites) were harvested from four GO patients for microarray analyses. Twelve candidate genes were selected for further quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR) analyses. Ten GO tissues from periodontitis patients and ten control gingival tissues from healthy subjects were compared by qRT-PCR. Mann-Whitney U-test was used for statistical evaluation. RESULTS: In GO positive tissues, 163-1631 up-regulated and 100-695 down-regulated genes were identified with more than two-fold changes compared with GO negative tissues amongst patients by microarray experiments. No commonly expressed genes amongst the eight sets of microarray data were found. The clustering analysis confirmed that the entire transcriptome patterns showed similarities in individuals, but differences amongst the four patients. The qRT-PCR and statistical analyses for the candidate genes, though, revealed differential gene expressions between GO-positive and negative tissues. We found that matrix metalloproteinase (MMP)-1 and MMP-12 as well as cathepsin-L were significantly up-regulated whilst keratin-10 and transforming growth factor-ß1 were significantly down-regulated in GO tissues of periodontitis patients compared with the control gingival tissues of healthy subjects. CONCLUSION: The microarray analyses revealed that GO pathogenesis was complex and individually varied, though GO-affected gingival tissues were controlled at least by genes related to collagen metabolisms including regulated MMPs, cathepsin-L, growth factors, and keratins to maintain tissue homeostasis in vivo.

Aggressive pregnancy tumor mimicking a malignant neoplasm: a case report.

AIM: The aim of this report is to present the management of an aggressive, highly proliferative pregnancy tumor with clinical and radiographic characteristics highly suggestive of a malignant neoplasm. BACKGROUND: Pregnancy tumor is a benign hyperplastic gingival lesion occurring during pregnancy that is indistinguishable from a pyogenic granuloma arising in nonpregnant females, or in males. The lesion usually grows over a few months and tends to bleed. CASE DESCRIPTION: A 28-year-old woman at four months of gestation was referred for a massive gingival swelling (5.5 cm in greatest diameter) on the mandibular left side. The lesion was painful and continued to grow very rapidly over a three-week period, with spontaneous bleeding, and it interfered with speech and mastication. Advanced alveolar bone loss also was found beneath the lesion. A malignant process was suspected, and an incisional biopsy revealed a pregnancy tumor. The lesion was excised under general anesthesia during the pregnancy with no untoward reactions. SUMMARY: Pregnancy tumor represents an important differential diagnosis of oral masses and can behave in a very aggressive fashion, mimicking a malignant tumor. CLINICAL SIGNIFICANCE: This lesion should always be included in the differential diagnosis of soft tissue masses in a pregnant woman even if the lesion is clinically very aggressive. It is acceptable practice to excise aggressive variants of this lesion during pregnancy to avoid distressing side effects.

Agrandamientos gingivales en niños y adolescentes transplantados renales / Gingival overgrowths in renal transplant children and adolescents

El receptor de transplante renal requiere terapia medicamentosa compleja con agentes inmunosupresores, corticoides, antimicrobianos, hipotensores y estimuladores de la regeneración ósea para prevenir el posible rechazo del órgano transplantado, controlar las infecciones secundarias a la inmunosupresión, las alteraciones de crecimiento y las variaciones de tensión arterial causadas por la insuficiencia renal. El objetivo de este trabajo fue analizar relación entre agrandamiento gingival y medicaciones recibidas. Fueron evaluados 47 niños y adolescentes transplatados renales, con edades entre 4 y 19 años (media 12.10 +- años) sin tratamiento preventivo bucal durante los 2 años previos a la iniciación del estudio, atendidos en el servicio de Nefrología del Hospital Nacional de Pediatría Juan P. Garrahan, de la Ciudad Autónoma de Buenos Aires, Argentina. Se analizó tipo de donante, tiempo de transplante y medicaciones inmunosupresoras (ciclosporina, micofenolato, azatioprina); corticoides (meprednisona), antimicrobianos (sulfametoxazol + trimetropina furantoína), hipotensores (enalapril, nifedipina); y estimuladores de la regeneración ósea (carbonato de calcio, 1 alfa 25-dihidroxicolecalciferol). Los resultados mostraron un agrandamiento gingival en el 69,6 por ciento de los niños y adolescentes, con un 31,9 por ciento de agrandamiento grado 3 y 4. Se observó correlación entre agrandamiento gingival y tiempo de trasplante P<0.05. No se observó asociación y correlación entre agrandamiento gingival y medicaciones.

Variáveis de risco associadas ao crescimento gengival em indivíduos transplantados renais sob regimes imunossupressores de ciclosporina, tacrolimus e sirolimus / Risk variables associated with gingival overgrowth in renal transplant recipients under immunosuppressive regimens based on cyclosporine, tacrolimus and sirolimus

Estudos sobre crescimento gengival (CG) e fatores de risco a ele relacionados em transplantados renais sob o uso dos imunossupressores ciclosporina A (CsA) e tacrolimus (Tcr) têm mostrado resultados diversos e não foram encontrados relatos sobre avaliações com sirolimus (Sir). Assim, o presente estudo, apresentado na forma de uma revisão de literatura e três artigos científicos, teve as seguintes propostas de investigação: 1) avaliar a prevalência, gravidade e variáveis de risco associadas ao CG nos regimes de imunossupressão baseados em Sir; 2) avaliar o polimorfismo do gene da interleucina-6 (IL-6) em indivíduos medicados com CsA, Tcr e Sir e sua associação com o CG; 3) avaliar a frequencia micorbiana e variáveis de risco para o CG nos regimes de imunissupressão baseados em CsA, Tcr e Sir. Uma amostra elegível foi seleciona em dois hospitais públicos de Belo Horizonte, Brasil. Participaram do estudo transplantados renais de ambos os gêneros, faixa etária variada, grupo racial heterogêneo, com no mínimo 6 dos 12 dentes anteriores. Os dados periodontais incluíram avaliação visual do CG, índice de placa e índice de sangramento papilar...

Gingival overgrowth in a renal transplant recipient using cyclosporine A.

Unsightly gingival enlargement is a frequent side effect in organ transplant recipients under immunosuppressive therapy with cyclosporin A (CsA). The purpose of this article was to report the treatment management of cyclosporin A-induced gingival overgrowth in a 9-year-old renal transplant recipient. Surgical reduction of the overgrown gingival tissue associated with an intensive biofilm control program and conversion from CsA to tacrolimus provided good clinical outcome with improvement of mastication, feeding, and phonetics. Gingival overgrowth stabilized with the change of medication. After approximately 3 months of follow-up, a regression of gingival enlargement was observed.

Orthodontic treatment of a patient with a renal transplant and drug-induced gingival overgrowth: a case report.

The treatment of transplant patients is becoming an ever-increasing part of modern-day orthodontic practice. This report details the successful orthodontic management of a paediatric renal transplant patient with significant drug-induced gingival overgrowth. The problems that such patients present with are discussed before considering the specific orthodontic techniques employed. Recommendations are made for practitioners managing such cases.

A ligneous periodontitis and conjunctival lesions in a patient with plasminogen deficiency.

Destructive membranous periodontal disease is a rare and poorly defined entity that is a part of a systemic disease due to accumulation of fibrin material. The disease is characterized by gingival enlargement and periodontal tissue destruction that leads to rapid bone loss despite treatment efforts. We present a case with ligneous periodontitis and conjunctivitis.

Gingival overgrowth with calcium-channel blockers. Treatment options.

Gingival overgrowth induced by calcium channel blockers can cause significant disfigurement and functional difficulty since it interferes with eating and speech, prevents effective plaque control, and disturbs occlusal relationships. It occurs more in young and male patients. The aim of this paper is to study the physiopathology of gingival overgrowth induced by calcium channel blockers and propose different choices of treatment.

High prevalence of Chlamydia pneumoniae infection in cyclosporin A-induced post-transplant gingival overgrowth tissue and evidence for the possibility of persistent infection despite short-term treatment with azithromycin.

BACKGROUND: Cyclosporin A (CsA) induces gingival overgrowth (GO) in up to a quarter of CsA-treated renal transplant recipients. A short-term therapy with azithromycin effectively reduces GO, indicating a possible involvement of microorganisms in the pathogenesis of CsA-induced GO. We aimed to determine if there could be any relationship between infection with Chlamydia pneumoniae and GO pathogenesis. In addition, we determined the long-term persistence rate of C. pneumoniae infection in residual GO tissue when azithromycin treatment failed to eliminate GO. METHODS: Chlamydia pneumoniae IgG and IgM antibody titres were measured by microimmunofluorescence technique in sera of kidney recipients with (n = 11) and without (n = 89) GO. GOs were rated and gingivectomies were performed before treatment with 500 mg of azithromycin for 3 days and at months 6 and 12 post-treatment when C. pneumoniae titres were re-evaluated. Nested polymerase chain reaction was performed to identify C. pneumoniae-specific DNA in GO tissues. Results of C. pneumoniae antibody titres from patients with GO were compared with pair-matched controls without GO. RESULTS: Chlamydia pneumoniae IgM titres were elevated in five of 11 patients with GO and in none without GO, whereas the difference of C. pneumoniae IgG titres between patients with GO and pair-matched controls did not reach significance (P<0.57). Chlamydia pneumoniae-specific DNA was found in 10 of 11 GO tissue samples pre-treatment. Azithromycin therapy effectively reduced GO and C. pneumoniae IgM titres. In residual GO, C. pneumoniae-specific DNA remained detectable after 1 year in all GO tissue samples despite azithromycin treatment. The C.pneumoniae IgM titres correlated with GO scores. CONCLUSION: Chlamydia pneumoniae infection is highly prevalent in CsA-induced GO. The infection can persist over a long period in residual GO despite short-term azithromycin therapy. The results indicate that CsA immunosuppression enhances C. pneumoniae infection rates in non-cardiovascular tissue.

Treating patients with drug-induced gingival overgrowth.

The purpose of this paper is to review the causes and describe the appearance of drug-induced gingival overgrowth, so that dental hygienists are better prepared to manage such patients. Gingival overgrowth is caused by three categories of drugs: anticonvulsants, immunosuppressants, and calcium channel blockers. Some authors suggest that the prevalence of gingival overgrowth induced by chronic medication with calcium channel blockers is uncertain. The clinical manifestation of gingival overgrowth can range in severity from minor variations to complete coverage of the teeth, creating subsequent functional and aesthetic problems for the patient. A clear understanding of the etiology and pathogenesis of drug-induced gingival overgrowth has not been confirmed, but scientists consider that factors such as age, gender, genetics, concomitant drugs, and periodontal variables might contribute to the expression of drug-induced gingival overgrowth. When treating patients with gingival overgrowth, dental hygienists need to be prepared to offer maintenance and preventive therapy, emphasizing periodontal maintenance and patient education. The affected gingiva presents a bulbous and irregular appearance and requires special modifications in the delivery of dental hygiene care. Dental hygienists play a vital role in the prevention and control of this condition because of the significant correlation between plaque/gingivitis and gingival overgrowth.

Subgingival microbiota of renal transplant recipients.

Renal transplant patients undergoing immunosuppressive therapy may experience periodontal side-effects such as gingival overgrowth. This study evaluated the subgingival microbiota of renal transplant recipients with or without periodontal tissue destruction who may have concurrent gingival enlargement. Subgingival paper point samples taken from the deepest probing sites of 38 subjects (one per patient) were examined using direct microscopy and culture techniques. A complex microflora comprising gram-positive and gram-negative cocci, rods and filaments, fusiforms, curved rods and spirochetes was observed using microscopy. Yeasts were occasionally detected. Significantly higher proportions of gram-positive morphotypes, including gram-positive cocci, were observed in samples from periodontally healthy patients. The predominant cultivable microflora from anaerobic culture comprised several species of facultative and obligate anaerobes. Colonization of the subgingival sites by 'foreign' microbes that are normally dermal, intestinal or vaginal flora was detected in up to 50% of the samples. High mean proportions of lost or unidentified species were also occasionally noted. The results showed that the subgingival biofilm of renal transplant recipients with chronic periodontitis comprised mainly gram-negative rods and spirochetes. Besides the usual predominant cultivable subgingival microbiota associated with periodontitis, the high prevalence of unidentified and 'foreign' microbes indicates the possibility of subgingival microbial alteration in renal transplant patients.

External cervical resorption associated with localized gingival overgrowth.

AIM: To describe the presentation and management of an unusual lesion of external cervical resorption. SUMMARY: The salient features of this unusual presentation of the external cervical resorption with localized gingival overgrowth, and the resorption located almost wholly on the labial aspect of a maxillary incisor crown are described. Extensive loss of enamel had occurred. The management and possible aetiology of the resorptive lesion are discussed. KEY LEARNING POINTS: Localized gingival overgrowth can be associated with external cervical resorption.The cervical resorption does not necessarily indicate pulp canal infection and the need for root-canal treatment.

Pathologic migration--spontaneous correction following periodontal therapy: a case report.

Periodontal disease is often associated with pathologic migration, which becomes an esthetic concern. A 17-year-old girl developed increasing gaps among her maxillary incisors. She had gingival enlargement in the palatal maxillary anterior region. The central incisors had pathologically migrated, resulting in a 2-mm diastema. Periodontal treatment was planned and completed. Following periodontal treatment, there was "spontaneous" repositioning of the central incisors. The 6-month follow-up revealed no change or deterioration of the periodontal condition. The patient was referred for orthodontic closure of the remaining diastema between the central and lateral incisors.

Drug-induced gingival overgrowth: a case with auto-correction of incisor drifting.

Drug-induced gingival overgrowth is an iatrogenic clinical condition, which affects a proportion of patients medicated for conditions such as hypertension, epilepsy and the prevention of organ transplant rejection. Clinical manifestation can vary in severity from minor problems to complete coverage of the standing teeth. Drifting of teeth can also occur, producing further aesthetic and functional problems for the patient. This report documents a case of a renal transplant patient in whom drifting of the upper incisor teeth spontaneously resolved following surgical reduction of the overgrown gingivae. Clinical issues relating to the management of gingival overgrowth are also discussed.

Oral giant pyogenic granulomas associated with facial skin hemangiomas (Sturge-Weber syndrome).

This is a case report of two patients, aged 26 and 22, who suffered from congenital hemangioma on their faces and pronounced gingival overgrowth localized parallel to extraoral lesions. Prior to surgical intervention the hygienic conditions were improved in several sessions by means of professional preventive treatment and oral hygiene instructions. Histologic examination of both cases revealed a highly vascularized pattern of pyogenic granuloma. One of the cases was associated with a pregnancy. These patients can be classified as Sturge-Weber syndrome. Postsurgical treatment consisted of efficient plaque control and adequate oral prophylaxis sessions every 3 months. The large gingival overgrowth was not observed to recur in 2 and 4 years, respectively, of follow-up.

Estudo do promotor do gene COL1A2 em portadores de fibromatose gengival hereditária / Study of the COL1A2 promoter from patients with hereditary gengival fibromatosis

A Fibromatose Gengival Hereditária (FGH) é uma condiçäo em que há aumento da secreçäo de proteínas da matriz extracelular, especialmente de colágeno tipo I. Condiçöes particulares individuais como polomorfismos genéticos ou mutaçöes poderiam influir na resposta de fibroblasto a estímulos do ambiente, provocando essa doença de causa ainda desconhecida. Assim, procuramos identificar polimorfismos ou mutaçöes na regiäo do promotor da cadeia alfa 2 do colágeno do tipo I (COL1A2) em um grupo de pacientes normais (n = 13). Além disso, testamos a hipótese de alteraçäo no padräo de metilaçäo dessa seqüência através da análise de metilaçäo. Foi feita a amplificaçäo por PCR da regiäo do promotor da cadeia alfa 2 do colágeno entre -340 e +2 pares de base (pb). Seguiu-se a análise de heteroduplex: aquecimento das amostras a 98§C por 5 minutos, resfriamento a 0§C, manutençäo a 20§C por uma hora e eletroforese em gel de poliacrilamida a 6 por cento. A análise de metilaçäo foi feita através do uso de enzimas de restriçäo (HAL III e HPA II, que näo clivam as suas seqüências da reconhecimento de Dna quando estas estiverem metiladas) previamente à reaçäo de PCR. Näo houve diferença na migraçäo dos fragmentos de DNA após a reaçäo de heteroduplex, nem foi determinada alteraçäo no padräo de metilaçäo entre os dois grupos de indivíduos. Esses achados indicam que mutaçöes ou alteraçöes no padräo de metilaçäo da regiäo do promotor do COL1A2, compreendida entre -340 e +2 pb, provavelmente näo estäo relacionadas ao crescimento gengival de portadores de FGH

Evaluation of gingival and periodontal conditions following causal periodontal treatment in patients treated with nifedipine and diltiazem.

It is established that phenytoin, cyclosporin and some calcium antagonists produce gingival overgrowth, but it is not known how this condition may respond to causal periodontal treatment. In order to find out, a longitudinal study was carried out, over a year, comparing a group of patients who were given nifedipine (NG, n = 18) and another group who were given diltiazem (DG, n = 13) with 2 others: one comprised cardiopathic patients who took no calcium antagonists (CG, n = 12) and the other contained patients who were medically healthy, with moderate periodontitis (HG, n = 12). On their basal visit, they were examined and instructed in oral hygiene, and then given causal periodontal treatment, being seen again at 4 and 8 months, when hygiene instructions were reinforced. They were seen for the last time at 12 months, when they were again examined. Groups NG and DG, on their basal visit, showed larger gum size than groups HG and CG, which was statistically significant; on their final visit, these differences remained only at the interproximal level. The number of patients with gingival overgrowth-taking the average of group HG as a minimal value-was much higher in groups CG (92%), DG (100%) and NG (89%) on the basal visit; on the final visit, the differences remained only in groups DG (85%) and NG (83%). The probing pocket depth reduction was much greater in groups HG and CG than in DG and NG, basically due to a greater gaining on clinical attachment level. The % of sites in which the pocket depth improved by more than 2 mm was 39.8% in HG, 54.5% in CG, 23.7% in DG and 28.7% in NG. The % of sites where the attachment gain by more than 2 mm was 46.2% in HG, 55.5% in CG, 22.8% in DG and 21.4% in NG. The amount of plaque and bleeding on probing, which was similar in all groups on the basal visit, decreased throughout the study, especially between the basal and 2nd visit in groups HG and CG. We have demonstrated that patients that take nifedipine and diltiazem show a larger gum size and their response to causal periodontal treatment is poorer than in the healthy and the cardiac groups.