Rare Diseases and COVID-19: How are the Patients?

Dear Editor, When searching the scientific literature COVID-19-associated syndromes in addition to syndromes middle eastern respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), some cardiovascular syndromes and post intensive care syndrome [1,2], we found the syndromes of Guillain-Barré, Miller Fisher, polyneuritis cranialis, Kawasaki, Inflammatory multisystem syndrome, and syndrome of inappropriate antidiuretic hormone secretion [3-29]. Of these, only Guillain-Barré syndrome and Miller Fisher syndrome, Kawasaki diseases and Inflammatory multisystem syndrome have currently present cranio-facial manifestation (Table 1), but possibly others will become know when the damage of COVID-19 becomes known.Although there is no standardized definition of rare diseases, the classification of rare diseases is closely related to a definition according to point prevalence in the current political and legislative context, and such definitions are based on a prevalence threshold directly or implied. According to the World Health Organization (WOS) and adopted by the Ministry of Health of Brazil, a rare disease affects up to 65 per 100,000 individuals [30]. Each rare disease, taken separately, affects a limited number of people. Considering, however, that there are up to 8,000 types of rare diseases worldwide, when grouped under a single category, their epidemiological impact may become quite significant. About 80% of those are caused by genetic factors, and the rest by other factors, such as environmental, infectious and immunologicalones [31]. Thus, rare diseases are a global challenge that must be overcome. A multi-professional and interdisciplinary team, including pediatric dentistry, oral medicine and pathology, is essential for success throughout the process

Orofacial features of Treacher Collins syndrome

Treacher Collins syndrome (TCS) is a rare autosomal dominant disorder of craniofacial development. Major features include midface hypoplasia, micrognathia, microtia, conductive hearing loss, and cleft palate. The present study is on the orofacial features of 7 Brazilian patients with sporadic TCS aged 4 to 38 years. All patients presented the typical down-slanting palpebral fissures, colobomas, zygomatic and mandibular hypoplasia, partial absence of the lower eyelid cilia, and abnormalities of the ears. Malocclusion was present in all patients, and an anterior open bite was found in 3 patients. None of the patients had a cleft palate

Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and/or palate in the Brazilian population

Background and Objective: Nonsyndromic cleft lip and/or palate (NSCL/P) is a complex disease associated with both genetic and environmental factors. One strategy for identifying of possible NSCL/P genetic causes is to evaluate polymorphic variants in genes involved in the craniofacial development. Design: We carried out a case-control analysis of 13 single nucleotide polymorphisms in 9 genes related to craniofacial development, including TBX1, PVRL1, MID1, RUNX2, TP63, TGFB3, MSX1, MYH9 and JAG2 , in 367 patients with NSCL/P and 413 unaffected controls from Brazil to determine their association with NSCL/P. Results: Four out of 13 polymorphisms (rs28649236 and rs4819522 of TBX1, rs7940667 of PVRL1 and rs1057744 of JAG2 ) were presented in our population. Comparisons of allele and genotype frequencies revealed that the G variant allele and the AG/GG genotypes of TBX1 rs28649236 occurred in a frequency significantly higher in controls than in the NSCL/P group (OR: 0.41; 95% CI: 0.25-0.67; p=0.0002). The frequencies of rs4819522, rs7940667 and rs1057744 minor alleles and genotypes were similar between control and NSCL/P group, without significant differences. No significant associations among cleft types and polymorphisms were observed. Conclusion: The study suggests for the first time evidences to an association of the G allele of TBX1 rs28649236 polymorphism and NSCL/P

[study Of Patients With Cleft Lip And Palate With Consanguineous Parents].

Cleft lip and/or palate (CL/P) are the most common congenital anomalies of the face. CL/P are non-syndromic (CL/PNS) in about 70% of subjects. To describe clinical cases of non-syndromic CL/P (CL/PNS) associated with consanguinity, diagnosed at a reference hospital in Minas Gerais, Brazil, and to correlate these alterations with possible risk factors. SERIES AND METHODS: A retrospective study at a reference hospital for craniofacial deformities in Minas Gerais, Brazil from 2006 to 2009 based on data in medical records. Of 246 CL/PNS cases diagnosed and treated at the institution, 15 (6.1%) were CL/PNS with reported first-degree consanguinity; 73.3% occurred in males. Four of 15 patients had complete right cleft palate and lip (CLP), 4 presented complete cleft palate and lip (right and left), 3 had complete unilateral left CLP, 3 had isolated cleft palate, and 1 presented cleft lip only. Among the risk factors, only three mothers reported smoking during pregnancy. CLP (unilateral or bilateral) were more frequent in the group with a history of first-degree consanguinity; males predominated. Among the risk factors, only smoking was observed in three cases.7719-2

Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study Efeitos da fluoxetina e imipramina em fetos de ratas tratadas durante o período crítico da gestação: estudo macro e microscópico

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p OBJETIVO: Avaliar as possíveis alterações ocorridas em nível macroscópico e microscópico de fetos de ratas submetidas ao tratamento com fluoxetina e imipramina durante o período "crítico" da gestação. MÉTODO: Quinze ratas, posteriormente ao acasalamento, foram divididas em três grupos experimentais (n = 5): G1, tratadas com 10mg/kg/dia de fluoxetina; G2, tratadas com 10mg/kg/dia de cloridrato de imipramina, e G3 (controle), tratadas com 10mg/kg/dia de solução fisiológica a 0,9%, no 9º, 10º e 11º dias de prenhez das ratas. Posteriormente à cesária, no 21º dia de prenhez, analisou-se macroscopicamente o peso fetal e placentário. Os fetos foram fixados e houve a remoção do encéfalo para pesagem e preparação das lâminas do tecido neuronal para contagem de neurônios do lobo frontal. RESULTADOS: O G1 e G2 apresentaram maior peso fetal. O G1 apresentou maior peso placentário, diferindo do G2 e G3 (p 0,01). O G3 exibiu maior número de neurônios, por área, do lobo frontal em relação a G1 e G2 (p < 0,01). CONCLUSÃO: A adoção dos antidepressivos causou, nos fetos, aumento de peso e redução da contagem de neurônios do lobo frontal, sugerindo que a indicação de antidepressivos às gestantes pode induzir a depressão nos fetos por alterações em seu neurodesenvolvimento

Association between maternal smoking, gender, and cleft lip and palate

ABSTRACT INTRODUCTION: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE: To assess the relationship between maternal smoking, gender and CL/P. METHODS: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: Cases: mothers of children with CL/P (n = 843) and Controls: mothers of children without CL/P (n = 676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. RESULTS: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR = 3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. CONCLUSION: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential

Association between maternal smoking, gender, and cleft lip and palate

Introduction: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. Objective: To assess the relationship between maternal smoking, gender and CL/P. Methods: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: Cases: mothers of children with CL/P (n = 843) and Controls: mothers of children without CL/P (n = 676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. Results: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR = 3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. Conclusion: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential. © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial815514519CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGsem informaçã

Tooth malposition in patients with cleft lip and/or palate in a Brazilian population

The purpose of the present study was to evaluate the prevalence of teeth malposition (rotated) in Brazilian patients with oral clefts and to contribute to the definition of subphenotypes. This study included 317 patients with nonsyndromic cleft lip with or without cleft palate. Tooth malposition was assessed clinically, through radiographs, and medical history records for each individual. Only teeth malpositions outside the area of the clefts were included. Comparisons were assessed by cross-tabulation and standard chi-square test, and statistical significance was set at p≤0.05. Cleft lip and palate was more prevalent in males, while cleft palate was more common in females. Regarding the presence of tooth malposition, of the 317 patients, 92 (29.02%) had at least one tooth with the dental anomaly. Tooth malposition was more common in patients with cleft lip and palate (16.1%), followed by, respectively, cleft palate (6.9%) and cleft lip (6%) (p=0.112). The highest occurrence of tooth malposition was in the mandible and involved the canines (p<0.01). Few studies have investigated the prevalence of tooth malposition in individuals with nonsyndromic cleft lip with or without cleft palate. Our results confirmed the highest occurrence of dental anomalies, particularly tooth malposition, in patients with oral clefts. Our findings also highlight that there was a higher occurrence of this condition in the mandible and not the maxilla

Avaliação da idade materna, paterna, ordem de paridade e intervalo interpartal para fissura lábio-palatina Maternal and paternal age, birth order and interpregnancy interval evaluation for cleft lip-palate

Fissuras do lábio e/ou palato representam as anomalias congênitas craniofaciais mais comuns. OBJETIVO: Avaliar fatores de risco ambientais em pacientes com fissuras lábio-palatinas não-sindrômicas, em um Serviço de Minas Gerais. CASUÍSTICA E MÉTODO: Realizou-se estudo caso-controle, avaliando 100 crianças com fissuras e 100 crianças sem alterações clínicas. As dimensões de análise (idade, cor de pele, sexo, classificação das fissuras, idade materna e paterna, ordem de paridade e intervalo interpartal) foram obtidas a partir de um questionário, sendo posteriormente construído banco de dados e as análises realizadas pelo programa SPSS 17.0. Os resultados foram analisados com risco relativo para cada variável, para estimar odds ratios com intervalo de confiança de 95% seguido de análise bivariada e multivariada. RESULTADOS: Entre as 200 crianças, 54% foram do sexo masculino e 46% do feminino. Com relação à cor da pele, houve predomínio de parda, branca e preta, respectivamente. Entre os tipos de fissuras, as mais comuns foram as fissuras lábio-palatinas (54%), seguidas pela fissura labial (30%) e fissura palatina (16%). CONCLUSÃO: Embora com uma população limitada, verificou-se associação entre idade materna e risco aumentado para fissuras lábio-palatinas, porém idade paterna, ordem de paridade e intervalo interpartal não foram significantes.<br>Cleft lip and palate (CL/P) are the most common congenital craniofacial anomalies. AIM: To evaluate environmental risk factors for non-syndromic CL/P in a reference care center in Minas Gerais. MATERIALS AND METHODS: we carried out a case-controlled study, assessing 100 children with clefts and 100 children without clinical alterations. The analysis dimensions (age, skin color, gender, fissure classification, maternal and paternal age, birth order and interpregnancy interval), obtained from a questionnaire; and later we build a data base and the analyses were carried out by the SPSS 17.0 software. The results were analyzed with the relative risk for each variable, in order to estimate the odds ratio with a 95% confidence interval, followed by a bivariate and multivariate analysis. RESULTS: among 200 children, 54% were males and 46% were females. As far as skin color is concerned most were brown, white and black, respectively. Cleft palates were the most common fissures found (54%), followed by lip cleft (30%) and palate cleft (16%). CONCLUSION: although with a limited sample, we noticed an association between maternal age and an increased risk for cleft lip and palate; however, paternal age, pregnancy order and interpregnancy interval were not significant

Ophthalmic changes in cleft lip and palate

ABSTRACT The current study aimed to analyze through a literature review evidence of association between ocular changes and non-syndromic cleft lip and/or palate (NSCL/P). A literature review was carried out in accordance with the Cochrane Collaboration Group protocol. PubMed, Scopus, Academic Google and ISI Web of Science databases were systematically searched. A total of 16 studies were accessed, and three made up the final sample.All three studied ocular abnormalities in patients with NSCL/P.The articles found ocular abnormalities in 6.21%, 17.54% and 1.03% of patients respectively.The presence of ocular abnormalities in patients with NSCL/P was significant in this systematic review, but the articles all agreed that future studies should explore the possibility of a greater occurrence of ocular changes in individuals with NSCL/P