Lívia Máris Ribeiro Paranaíba

Region 8q24 is a susceptibility locus for nonsyndromic oral clefting in Brazil

BACKGROUND Nonsyndromic cleft lip with or without cleft palate is a relatively common craniofacial defect with multifactorial inheritance. The association of the rs987525 single nucleotide variant, located in a gene desert at 8q24.21 region, has been consistently replicated in European populations. We performed a structured association approach combined with transcriptional analysis of the MYC gene to dissect the role of rs987525 in oral clefting susceptibility in the ethnically admixed Brazilian population. METHODS We performed the association study conditioned on the individual ancestry proportions in a sample of 563 patients and 336 controls, and in an independent sample of 221 patients and 261 controls. The correlation between rs987525 genotypes and MYC transcriptional levels in orbicularis oris muscle mesenchymal stem cells was also investigated in 42 patients and 4 controls. RESULTS We found a significant association in the larger sample (p = 0.0016; OR = 1.80 [95% confidence interval {CI}, 1.21-2.69], for heterozygous genotype, and 2.71 [95% CI, 1.47-4.96] for homozygous genotype). We did not find a significant correlation between rs987525 genotypes and MYC transcriptional levels (p = 0.14; r = -0.22, Spearman Correlation). CONCLUSIONS We present a positive association of rs987525 in the Brazilian population for the first time, and it is likely that the European contribution to our population is driving this association. We also cannot discard a role of rs987515 in MYC regulation, because this locus behaves as an expression quantitative locus of MYC in another tissue.

Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population

BACKGROUND Polymorphisms in genes that are involved in folic acid metabolism may be important maternal risk factors for the birth of a child with nonsyndromic cleft lip and/or palate (NSCL/P). The aim of this study was to determine the involvement of polymorphic variants in four genes (MTHFR, MTHFD1, MTR, and SLC19A1) that encode proteins related to folic acid metabolism in the women with susceptibility for having a child with NSCL/P. METHODS DNA samples from 106 mothers of children with NSCL/P (case group) and from 184 mothers of healthy children (control group) were genotyped by polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFLP). RESULTS One of 29 polymorphisms was associated with significantly increased maternal risk for NSCL/P. Mothers exhibiting the A variant allele (GA genotype) of the MTHFR rs2274976 polymorphism demonstrated a ~6 times increased risk for having a child with NSCL/P compared to G allele carriers (OR, 5.76; 95% CI, 3.32-9.99, p = 0.000001). Among mothers who did not use vitamins, the OR of NSCL/P was increased to 8.34 (95% CI, 3.75-18.55, p = 0.000001) in the presence of the GA genotype of the MTHFR rs2274976 polymorphism compared to those with the GG genotype. Gene-gene interaction analysis showed that the combination of MTHFR rs2274976, MTHFD1 rs2236225, and SLC19A1 rs1051266 was the best model for prediction of maternal risk for NSCL/P. CONCLUSION The findings of the present study suggested that genetic variants of folic acid metabolic genes may modulate maternal susceptibility for having an offspring with NSCL/P.

Goldenhar syndrome: clinical features with orofacial emphasis

OBJECTIVES Goldenhar syndrome (GS) is a relatively common developmental disorder characterized by craniofacial anomalies in association with vertebral, cardiac, renal, and central nervous system defects. This paper describes GS features with special emphasis on oral characteristics. MATERIAL AND METHODS The clinical features of 6 patients with GS aged 3 months to 12 years are described, and a brief review of the literature about this genetic disorder is presented. RESULTS All patients demonstrated the classical triad of GS, including mandibular hypoplasia resulting in facial asymmetry, ear and/or eye malformation, and vertebral anomalies. In addition, renal and gastrointestinal abnormalities were observed in 2 patients. Regarding the oral involvement, 2 patients presented cleft lip and palate, and 1 patient had temporomandibular joint malformation. Malocclusion was found in all patients. CONCLUSION Our orofacial findings correlate with the reported cases in the literature, and point out that after diagnosis GS patients need to be examined for systemic abnormalities.

Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population

Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population Elizabete Bagordakis, L ivia M aris Ribeiro Paranaiba, Luciano Abreu Brito, Sibele Nascimento de Aquino, Ana Camila Messetti, Herc ilio Martelli-Junior, Mario Sergio Oliveira Swerts, Edgard Graner, Maria Rita Passos-Bueno, and Ricardo D. Coletta* Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, S~ao Paulo, Brazil Stomatology Clinic, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil Human Genome Research Center, Institute of Biosciences, University of S~ao Paulo, S~ao Paulo, Brazil Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of Jos e Ros ario Vellano, Minas Gerais, Brazil

Prevalence of Dental Anomalies in Patients With Nonsyndromic Cleft Lip and/or Palate in a Brazilian Population.

Objective Many studies have demonstrated a high frequency of dental anomalies in patients with cleft lip and/or palate. Because dental anomalies may complicate dental treatment, we investigated the prevalence of dental anomalies in a group of Brazilian patients with nonsyndromic cleft lip and/or palate. Design, Participants, Setting Retrospective analysis was performed using clinical records of 296 patients aged between 12 and 30 years with repaired nonsyndromic cleft lip and/or palate without history of tooth extraction and orthodontic treatment. Associations between oral clefts and presence of dental anomalies outside the cleft area were investigated. Results Dental anomalies were identified in 39.9% of the nonsyndromic cleft lip and/or palate patients, and tooth agenesis (47.5%), impacted tooth (13.1%), and microdontia (12.7%) were the most common anomalies. Cleft lip patients were less affected by dental anomalies compared with cleft palate or cleft lip and palate patients (p = .057). Specifically, patients with unilateral cleft lip and palate were significantly more affected by dental anomalies than those with bilateral cleft lip and palate (p = .00002), and individuals with unilateral complete cleft lip and palate (p = .002) and complete cleft palate (p = .01) were significantly more affected by tooth agenesis than other cleft types. Agenesis of the premolars (p = .043) and maxillary lateral incisors (p = .03) were significantly more frequent in patients with unilateral complete cleft lip and palate. Conclusions The present study revealed a high frequency of dental anomalies in nonsyndromic cleft lip and/or palate patients and further demonstrated that patients with unilateral cleft lip and palate were frequently more affected by dental anomalies than those with bilateral cleft lip and palate. Moreover, our results demonstrate that dental anomalies should be considered during dental treatment planning for individuals affected by nonsyndromic cleft lip and/or palate.

Fissuras lábio-palatinas: série de casos clínicos incomuns

Fissuras do labio e/ou palato (FL/P) representam as anomalias congenitas mais comuns da face, correspondendo a aproximadamente 65% de todas as malformacoes da regiao craniofacial. OBJETIVO: Descrever casos clinicos incomuns de FL/P nao-sindromicas (FL/PNS), diagnosticadas em um Servico de referencia em Minas Gerais, Brasil, e correlacionar tais alteracoes com possiveis fatores de risco. CASUISTICA E METODOS: Realizou-se estudo retrospectivo, entre os anos de 1992 e 1o semestre de 2009, a partir dos prontuarios clinicos. RESULTADOS: Entre 778 casos de FL/PNS diagnosticadas no periodo de 17 anos, 5 (0,64%) foram de FL/PNS incomuns, sendo todos os pacientes do genero masculino. Verificou-se que, dos 5 pacientes, 2 apresentaram fissura labial direita incompleta associada a fissura palatina incompleta; 2 eram afetados por fissura labial esquerda incompleta e fissura palatina incompleta e 1 com fissura labio-palatina esquerda completa e fissura palatina direita completa. Fatores de risco como consanguinidade, tabagismo e etilismo materno, uso de medicamento na gestacao, historico de aborto e/ou natimorto e doencas maternas nao foram associados as FL/ PNS incomuns CONCLUSOES: Este estudo descreveu 5 casos raros de FL/PNS em uma populacao brasileira, nao apresentando correlacao com os fatores de risco analisados. Confirmou-se ainda a raridade na prevalencia de tais alteracoes.UNLABELLED Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face, corresponding to approximately 65% of all malformations of the craniofacial region. AIM to describe unusual clinical cases of non-syndromic CL/P (CL/PNS), diagnosed in a reference service in Minas Gerais, Brazil, and correlate these alterations with possible risk factors. MATERIALS AND METHODS we carried out a retrospective study, between the years of 1992 and the 1st half of 2009, from medical records. RESULTS Among the 778 cases of CL/PNS diagnosed in the period of 17 years, 5 (0.64%) were unusual CL/PNS, and all patients were male. It was found that among the 5 patients, 2 had incomplete right cleft lip with incomplete cleft palate, 2 were affected by left incomplete cleft lip and incomplete cleft palate, and 1 had a cleft lip and palate associated with complete right cleft palate. Risk factors such as consanguinity, maternal smoking and alcohol consumption, medication usage during pregnancy, history of abortion and/or stillbirths and maternal diseases were not associated with unusual CL/PNS. CONCLUSIONS This study described 5 unusual cases of CL/PNS in a Brazilian population; no associations with the risk factors analyzed were seen. It also confirmed the unusualness of the prevalence of such alterations.

Orofacial Features of Hypohidrotic Ectodermal Dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a type of genodermatosis characterized by the abnormal development of sweat glands, teeth, and hair. The most prevalent form of HED is X-linked hypohidrotic ectodermal dysplasia (XLHED), which is associated with mutations in the EDA gene. The aim of this case report was to describe a family with XLHED with emphasis on differences in orofacial features between members. Family members were systematically evaluated to characterize the pattern of inheritance and clinical features. Dental examination included evaluation of agenesis and abnormal teeth structure. The pedigree of the last seven generations of the family was constructed. Clinical examination and medical history revealed five males affected by HED and nine female as heterozygous carriers. The males exhibited the classic phenotype of XLHED, with dental abnormalities, hypohydrosis, and craniofacial dysmorphologies. The heterozygous carriers of the X-linked gene defect principally exhibited dental agenesis of the lateral maxillary incisors. Careful clinical examination, including dental evaluation, is an important way to detect heterozygous carriers of X-linked HED. Heterozygous parents of patients with HED may also show some features of the disorder. The identification of female carriers results in genetic counseling being offered to affected families, as well as providing adequate treatment as necessary and long-term follow-up of these patients.

Frequency of congenital craniofacial malformations in a Brazilian Reference Center

OBJECTIVE: To evaluate the frequency of craniofacial anomalies in patients treated at a Brazilian Reference Center for craniofacial deformities. METHOD: Retrospective epidemiological study evaluating the clinical records of 1,142 patients: 656 (57.4%) male and 486 (42.6%) female, between 1992 and 2008. RESULTS: Among birth defects, non-syndromic cleft lip and/or palate were the most frequent ones (778 cases; 68.1%), followed by single or multiple congenital anomalies without cleft lip and/or palate (240 cases; 21%), recognized syndromes or sequences (56 cases; 5%), syndromes with orofacial cleft as a component (41 cases; 3.5%), and orofacial clefts in association with systemic malformations (27 cases; 2.4%). CONCLUSIONS: Non-syndromic cleft lip and/or palate was the congenital defect most frequently identified, although, isolated anomalies and syndromes involving craniofacial structures were quite frequent. Furthermore, the need for studies to identify the frequency and risk factors associated with craniofacial anomalies in the Brazilian population is emphasized in order to plan comprehensive strategies and integrated actions for the development of preventive programs and treatment.OBJETIVO: Avaliar a frequencia de anomalias craniofaciais em pacientes assistidos em um Centro de Referencia Brasileiro para deformidades craniofaciais. METODO: Estudo retrospectivo epidemiologico avaliando os prontuarios clinicos de 1.142 pacientes, sendo 656 (57,4%) do genero masculino e 486 (42,6%) do feminino, entre os anos de 1992 e 2008. RESULTADOS: Entre os defeitos congenitos, fissura labial e/ou palatina nao-sindromica foi o mais frequente (778 casos; 68,1%), seguido por anomalias congenitas simples ou multiplas sem fissura labial e/ou palatina (240 casos; 21%), sindromes ou sequencias reconhecidas (56 casos; 5%), sindromes com fissura orofacial como um componente do quadro sindromico (41 casos; 3,5%), e fissuras orofaciais em associacao com malformacoes sistemicas (27 casos; 2,4%). CONCLUSOES: Observou-se que o defeito congenito identificado mais frequente foi a fissura labial e/ou palatina nao-sindromica, no entanto, anomalias isoladas e sindromes envolvendo as estruturas craniofaciais foram bastante encontradas. Alem disso, ressalta-se a necessidade de estudos que identifiquem a frequencia e os fatores de riscos associados as anomalias craniofaciais na populacao brasileira, a fim de que se planejem estrategias e acoes integradas para o desenvolvimento de programas preventivos e de tratamento adequado.

Sífilis materna e congênita, subnotificação e difícil controle

OBJECTIVE To identify and to describe cases of congenital and maternal syphilis reported and not reported in a Brazilian medium-sized city. METHODS This is a descriptive and retrospective study, which evaluated 214 medical records of pregnant women and newborns. It began with the identification of epidemiological notification records, followed by active search in maternity evaluating all records that did show positive nontreponemal serology and records of the reference service in infectious diseases in Montes Claros, Minas Gerais, from 2007 to 2013. The case definitions followed the Ministry of Health recommendations in Brazil and the variables were described using absolute and relative frequencies. This study was approved by the Ethics in Research Committee (University State of Montes Claros). RESULTS Of the 214 medical records, we identified 93 cases of maternal syphilis and 54 cases of congenital. The women studied were predominantly mulatto, with Secundary/Higher, aged between 21 and 30 years and single marital status. Considering the prenatal care of pregnant women with syphilis, it was observed predominance of late diagnosis, after parturition or curettage, and all of their treatments were considered inadequate according the Ministry of Health. The newborns of pregnant women with syphilis, most were not referenced for pediatric follow-up. Only 6.5% of syphilis in pregnant women was notified, and in congenital syphilis, 24.1%. CONCLUSION Persisting vertical transmission, there are signs that the quality of prenatal and neonatal care should be restructured.

Prevalence of depressive symptoms in patients with cleft lip and palate.

INTRODUCTION Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE To evaluate the prevalence of depressive symptoms in children and adolescents with nonsyndromic cleft lip and/or palate (nsCL/P). METHODS We conducted an observational, case-control study, with a case study group composed of 61 patients with nsCL/P, aged 7-17 years, and a control group of 61 clinically normal patients. Both groups were selected at the same institution. RESULTS Depressive symptoms were observed in the case group (nsCL/P), but there were no statistically significant differences compared to the control group. No association was found between the two groups (case and control) in relation to sociodemographic variables: gender, age and education. CONCLUSIONS This study identified the prevalence of depressive symptoms in children and adolescents with nsCL/P from a localized geographic population, although the results were not statistically significant when compared to the control group, not justifying the use of CDI (Child Depression Inventory) as a screening instrument for depressive symptoms in the examined population.