Oral and dental alterations and growth disruption following chemotherapy in long-term survivors of childhood malignancies.

PURPOSE: More attention has been focused on the long-term side effects of treatment protocols since impressive advances in childhood cancer treatment have resulted in a growing population of patients. The purpose of this study was to investigate the disturbances of dento-facial development in children who were long-term survivors of childhood malignancies. METHODS: Fifty-three children (mean age, 10 years + 4 months) in long-term remission underwent oral/dental and radiographic examinations after completion of therapy. Crown and root malformations, gingival/periodontal status, enamel defects, discolorations, decayed and unerupted teeth, premature apexifications, agenesis, maximal interincisal opening and lateral movement of jaws, and soft tissue abnormalities were noted. Caries were evaluated by the decayed-missing-filled teeth (DMFT) index. Forty healthy children (mean age, 12 years + 4 months) belonging to the same age group and socioeconomic community were served as controls. All participants in the study were evaluated in terms of craniofacial development. RESULTS: The data of the study showed that higher prevalence of root malformation, unerupted teeth, and enamel hypoplasia were detected as a consequence of childhood cancer and/or antineoplastic therapy. Although no differences of craniofacial growth and development were observed between groups (P > 0.05), plaque and gingival index scores were statistically higher in the study group (P < 0.05). CONCLUSION: A range of variations in dental structures is recognized as a side effect of childhood cancer therapy in long-term survivors of pediatric malignancies that may affect their quality of life.

Ellis-Van Creveld Syndrome in a Neonate.

Ellis-van Creveld syndrome is a rare form of skeletal and chondroectodermal dysplasia which affects all the three ectodermal, mesodermal, and endodermal derivatives. It has an autosomal recessive inheritance. This is caused by mutations in 1 of 2 genes, EVC 1 or EVC 2. This syndrome has a constellation of characteristic features that include bilateral post-axial polydactyly, mainly involving the upper limbs, hypoplastic nails and teeth, congenital heart defects, and chondroectodermal dysplasia. It is mainly a disorder of Amish population where incidence of this disease is 1/5000 and its incidence in non-Amish population is 7/1000000. Our patient had all the major characteristic features consistent with Ellis-van Creveld syndrome including post-axial polydactyly, teeth and nail abnormalities, congenital heart defect and skeletal dysplasia. Until now, only five cases have been reported from this region of the world, none of them diagnosed in neonatal life and having characteristic common atrium.

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report.

We described herein the oral and craniofacial features of a 7-year-old boy, diagnosed in utero with mucopolysaccharidosis II (MPS II), who was treated with hematopoietic stem cell transplantation (HSCT) at 70 days of age. The main oral clinical findings were the following: macroglossia, posterior cross-bite, crowding, pointed cuspid teeth, delayed tooth eruption, retained primary teeth, and enamel hypoplasia. The image examination showed: retention eruption, posterior primary teeth with short roots, absence of some permanent teeth, and stretching of the stylohyoid processes bilaterally. This patient showed the importance of early diagnosis and HSCT therapy in attenuating the clinical and radiographic oral and craniofacial manifestations of the MPS II patient.

Prevalence of Orofacial Clefts among Live Births in China: A Systematic Review and Meta-Analysis.

BACKGROUND: Orofacial clefts (OFCs) are common human birth defects in China. However, studies on the prevalence of OFCs present inconsistent results. The overall prevalence and geographic distribution of OFCs are poorly described in China. Thus, we conducted a systematic review and meta-analysis to estimate the prevalence of OFCs. METHODS: The systematic review and meta-analysis were conducted on the basis of an established protocol (PROSPERO 2015: CRD42015030198). We systematically searched for articles in four electronic databases, including Embase, PubMed, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify relevant studies about prevalence of OFCs in China. Meta-analysis, including subgroup analysis, was conducted to estimate the pooled prevalence. RESULTS: A total of 41 studies published between 1986 and 2015 were included in our analysis. The sample size ranged from 2,586 to 4,611,808 live births. The random-effects model of meta-analysis showed that the overall prevalence of OFCs in China was 1.4 per 1000 live births (95% confidence interval [CI], 1.1-1.7). In subgroup analysis based on geographic regions, we found that OFC prevalence in Southwest (2.3 per 1000 live births, 95% CI, 1.1-4.7) was higher than that in other regions of China. There were no significant time trends of OFCs during the study period (p-value = 0.47). CONCLUSION: The overall prevalence of OFCs in China was 1.4 per 1000 live births. No significant secular trend of prevalence has been found in this analysis. Further studies need to be conducted to explore the etiology of OFC to better control the risk of this common birth defect. Birth Defects Research 109:1011-1019, 2017. © 2017 Wiley Periodicals, Inc.

Is it safe to use lamotrigine during pregnancy? A prospective comparative observational study.

BACKGROUND: Lamotrigine is a second-generation antiepileptic drug, also used as a mood stabilizer. Published data on its use in human pregnancy are largely derived from pregnancy registries. Pregnancy experience in most studies has been reassuring. However, data from the North American Antiepileptic Drug Pregnancy Registry suggested an increased risk for oral clefts. The primary objective of the study was to evaluate the rate of major anomalies after lamotrigine exposure during pregnancy compared with pregnancies of women counseled for nonteratogenic exposure (NTE). METHODS: Callers who contacted the Israeli Teratology Information Service regarding lamotrigine treatment or NTE during pregnancy between 1997 and 2008 were prospectively followed-up. RESULTS: The rate of major congenital anomalies was similar between 218 lamotrigine exposed pregnancies (208 in the first trimester) and 865 NTE-pregnancies. There was no case of oral cleft in the lamotrigine-exposed group. The median lamotrigine dose in the beginning of pregnancy was 200 mg/d. The dose was increased during pregnancy in 29%. The majority of women in the cohort (82%) were treated for neurologic indications, while 18% for psychiatric disorders. Monotherapy was taken by 72%. CONCLUSION: The data available, thus far, on lamotrigine monotherpy-exposed pregnancies are encouraging. However, further studies are needed to determine with greater certainty the overall risk for major anomalies, as well as the specific risk for oral clefts. Based on the current and previously published data, lamotrigine, seems a reasonable alternative for pregnant women when clinically indicated. Birth Defects Research 109:1196-1203, 2017. © 2017 Wiley Periodicals, Inc.

Neighborhood Deprivation and Risk of Congenital Heart Defects, Neural Tube Defects and Orofacial Clefts: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs). METHODS: We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models. RESULTS: Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61). CONCLUSION: In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association.

Dry mouth: Xerostomia and salivary gland hypofunction.

BACKGROUND: Mouth dryness may present as salivary gland hypofunction (SGH), xerostomia or both. It is considered one of the most underappreciated, underdiagnosed and undermanaged oral health conditions. Despite its common presentation and adverse impact on life quality, it is also generally poorly understood. Increased awareness of the condition is important in addressing these problems. OBJECTIVE: This article discusses SGH and xerostomia, and the associated intra-oral and extra-oral implications. It also summarises currently available management approaches and the evidence behind them. DISCUSSION: SGH and xerostomia are complex problems. None of the currently available management approaches are entirely satisfactory. Addressing the causative or contributing factors is therefore paramount. While oral health complaints are generally left up to the dental professional to manage, the nature of mouth dryness necessitates increased dialogue between the dental and medical professions to ensure optimal patient care.

Tongue-tie and frenotomy in infants with breastfeeding difficulties: achieving a balance.

AIMS: Currently there is debate on how best to manage young infants with tongue-tie who have breastfeeding problems. One of the challenges is the subjectivity of the outcome variables used to assess efficacy of tongue-tie division. This structured review documents how the argument has evolved. It proposes how best to assess, inform and manage mothers and their babies who present with tongue-tie related breastfeeding problems. METHODS: Databases were searched for relevant papers including Pubmed, Medline, and the Cochrane Library. Professionals in the field were personally contacted regarding the provision of additional data. Inclusion criteria were: infants less than 3 months old with tongue-tie and/or feeding problems. The exclusion criteria were infants with oral anomalies and neuromuscular disorders. RESULTS: There is wide variation in prevalence rates reported in different series, from 0.02 to 10.7%. The most comprehensive clinical assessment is the Hazelbaker Assessment Tool for lingual frenulum function. The most recently published systematic review of the effect of tongue-tie release on breastfeeding concludes that there were a limited number of studies with quality evidence. There have been 316 infants enrolled in frenotomy RCTs across five studies. No major complications from surgical division were reported. The complications of frenotomy may be minimised with a check list before embarking on the procedure. CONCLUSIONS: Good assessment and selection are important because 50% of breastfeeding babies with ankyloglossia will not encounter any problems. We recommend 2 to 3 weeks as reasonable timing for intervention. Frenotomy appears to improve breastfeeding in infants with tongue-tie, but the placebo effect is difficult to quantify. Complications are rare, but it is important that it is carried out by a trained professional.

Knowledge of Nairobi East District Community Health Workers concerning HIV-related orofacial lesions and other common oral lesions.

BACKGROUND: Human immunodeficiency virus (HIV) related orofacial lesions (HROLs) impact negatively on the health of patients and could be managed at primary healthcare (PHC) level. Community health workers (CHWs) are crucial in optimal patient management through patient identification, education and early referral for professional care. The study objective was to assess knowledge of Nairobi East district CHWs regarding HROLs and other common oral diseases. METHODS: Of the total population of CHWs, 815 [94.5%] completed a 56-item questionnaire covering 5 topics: general dental knowledge, knowledge about HROLs, past encounters with HROLs, current care at community level, opinions regarding oral health problems; and items concerning background characteristics and past training activities. Confirmatory factor analysis revealed Cronbach's alpha coefficient values of 0.45, 0.59, 0.79, 0.50 and 0.09 respectively. The first four topics were confirmed as domains. Mean minimum score was 0 and mean maximum score was 1 for each variable. However, for 'past encounters with HROLs, the minimum score was 0 and maximum score was 5. RESULTS: CHWs had moderate knowledge about general oral health (mean = 0.47) and HROLs (mean = 0.43). None had been formally trained in oral health aspects. Although they had high opinions regarding their role in identifying, educating and referring patients with HROLs (mean = 0.80) to the health facilities, they actually rarely referred such patients. CONCLUSIONS: CHWs need training for building competence in promoting oral health among general and HIV patients in their communities and in early identification and management of non-HIV oral lesions.

Oral manifestations of hereditary nonpolyposis colorectal cancer syndrome: a family case series.

INTRODUCTION: Hereditary nonpolyposis colorectal cancer is a colorectal cancer syndrome characterized by the development of colorectal cancer and extracolonic tumors, and this syndrome has an autosomal dominant mode of inheritance. To our knowledge, our study was the first to find dento-osseous anomalies and the second to observe Fordyce granules in a family with individuals with hereditary nonpolyposis colorectal cancer. CASE PRESENTATIONS: Twenty members of one Brazilian family with individuals with hereditary nonpolyposis colorectal cancer were analyzed according to the presence of colorectal cancer and the occurrence of Fordyce granules and dento-osseous anomalies. Their average age was 29.6 (range 7 to 53 years) years. Medical examinations of this family with hereditary nonpolyposis colorectal cancer were performed at the Coloproctology Division of our hospital. Then, all individuals were referred to our Oral Care Center for Inherited Diseases for intraoral examinations to verify the presence of Fordyce granules. Dental panoramic radiographs were done in order to describe dento-osseous anomalies on applying the Dental Panoramic Radiograph System. Of the 20 family members, four were diagnosed with hereditary nonpolyposis colorectal cancer and all four presented Fordyce granules in their upper lip, but only one of these four patients (Case 2) had a significant dento-osseous anomaly. CONCLUSIONS: Our familial study verified the presence of Fordyce granules in all individuals diagnosed with hereditary nonpolyposis colorectal cancer, and the presence of significant dento-osseous anomalies in one of these cases. However, the relationship between oral manifestations and hereditary nonpolyposis colorectal cancer should be further investigated.

Prosthodontic rehabilitation in patient with ectodermal dysplasia combining preprosthetic techniques: a case report.

Oral manifestations in ectodermal dysplasia include oligodontia, alveolar ridges hypoplasia, and others. Due to the special conditions in terms of unhealthy teeth and lack of bone, implant-supported rehabilitation seems to offer the most satisfactory outcome. A 27-year-old male diagnosed with ectodermal dysplasia was referred to our department for oral rehabilitation. Oral manifestations included oligodontia, maxillary and mandibular atrophy, mandibular alveolar ridge with knife-edge morphology, and conical teeth. Treatment planning consisted of a Le Fort I osteotomy with interpositional grafts, bilateral sinus lift, and placement of maxillary and mandibular inlay and onlay corticocancellous grafts, using autologous iliac crest bone. In the second surgery, all remaining teeth were removed and 11 endosteal implants were placed. Six months after implant placement, a bimaxillary fixed implant-supported prosthesis was delivered, maintaining a satisfactory esthetic and functional result after a 2-year follow-up. The use of combined preprosthetic techniques allows the placement of endosteal implants and a fixed implant-supported prosthesis in patients with oligodontia and ectodermal dysplasia, providing an esthetic and functional oral rehabilitation.

The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California.

Congenital anomalies are a leading cause of infant mortality and are important contributors to subsequent morbidity. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited. We aimed to investigate whether ambient air pollutant and traffic exposures in early gestation contribute to the risk of selected congenital anomalies in the San Joaquin Valley of California, 1997-2006. Seven exposures and 5 outcomes were included for a total of 35 investigated associations. We observed increased odds of neural tube defects when comparing the highest with the lowest quartile of exposure for several pollutants after adjusting for maternal race/ethnicity, education, and multivitamin use. The adjusted odds ratio for neural tube defects among those with the highest carbon monoxide exposure was 1.9 (95% confidence interval: 1.1, 3.2) compared with those with the lowest exposure, and there was a monotonic exposure-response across quartiles. The highest quartile of nitrogen oxide exposure was associated with neural tube defects (adjusted odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). The adjusted odds ratio for the highest quartile of nitrogen dioxide exposure was 1.7 (95% confidence interval: 1.1, 2.7). Ozone was associated with decreased odds of neural tube defects. Our results extend the limited body of evidence regarding air pollution exposure and adverse birth outcomes.

Maternal bereavement in the antenatal period and oral cleft in the offspring.

STUDY QUESTION: Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring? SUMMARY ANSWER: Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child. WHAT IS KNOWN ALREADY: The aetiology of oral cleft is unknown but includes both genetic and environmental causes. STUDY DESIGN, SIZE AND DURATION: We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies. LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers. WIDER IMPLICATIONS OF THE FINDINGS: With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.

Dental findings and special care in patients with Angelman syndrome: a report of three cases.

Angelman syndrome (AS) is a neurogenetic disorder, characterized by intellectual disability, movement or balance disorders, specific abnormal behaviors, and severe speech and language limitations. Due to its low incidence and the nonspecifity of developmental problems in newborns and young children, AS is not easily identified by clinical pediatricians. The aim of this paper is to present three cases of AS, reporting the orofacial characteristics and requisite dental care in these patients. Interestingly, this investigation found that certain typical features of mouth breathing syndrome, such as long and narrow faces, open mouth, shortened upper lip, lowered mandible position, shadows under the eyes (infraorbital cyanosis), muscular hypotonia, and enlarged and anteriorized tongue, were present in the three studied AS patients.

Dental and oral anomalies in incontinentia pigmenti: a systematic review.

OBJECTIVES: Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a mutation of the IKBKG gene. The objective of this study was to present a systematic review of the dental and oral types of anomalies, to determine the total number and sex distribution of the anomalies, and to analyze possible therapies. MATERIALS AND METHODS: We analyzed the literature data from 1,286 IP cases from the period 1993-2010. RESULTS: Dental and/or oral anomalies were diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types were dental, and the most frequent of these were dental shape anomalies, hypodontia, and delayed dentition. The most frequent oral anomaly types were cleft palate and high arched palate. IKBKG exon 4-10 deletion was present in 86.36% of genetically confirmed IP patients. CONCLUSIONS: According to the frequency, dental and/or oral anomalies represent the most frequent and important IP minor criteria. The most frequent mutation was IKBKG exon 4-10 deletion. The majority of dental anomalies and some of the oral anomalies could be corrected. CLINICAL RELEVANCE: Because of the presence of cleft palate and high arched palate in IP patients, these two anomalies may be considered as diagnostic IP minor criteria as well.

Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts.

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

Dental aspects in patients with DiGeorge syndrome.

DiGeorge syndrome, which is caused by a microdeletion of 1.5 to 3.0 megabases on the long arm of chromosome 22, has an incidence of approximately 1:4,000 to 1:5,000 live births. The phenotypic spectrum of this disorder includes congenital heart defects, immunodeficiency due to thymic hypoplasia or aplasia, transient or permanent hypocalcemia due to parathyroid hypoplasia or aplasia, developmental retardation, and psychiatric disorders. Dental aspects in these patients include skeletal malformations, velopharyngeal insufficiency with or without cleft palate, small mouth, and hypotonus orofacial musculature, as well as impaired salivary flow. Enamel aberrations related to hypocalcemia may result in a higher frequency of dental caries. Based on a series of five patients, the medical and dental aspects that have to be considered in the care of patients with DiGeorge syndrome are presented.