RESUMO
OBJECTIVE: To identify, critically evaluate and synthesize the evidence obtained from systematic reviews on the association between genetic polymorphisms and osteoarthritis (OA) development. METHODS: Considering gene polymorphisms associated with OA susceptibility (risk or protection), a comprehensive search was conducted in the following databases, without date or language restrictions: MEDLINE, via Pubmed; Embase, via Elsevier; Cochrane Database of Systematic Reviews, via Wiley; Biblioteca Virtual em Saúde. Gray literature was also searched through the OpenGrey database. The AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews) was used to assess the methodological quality of the included systematic reviews. RESULTS: We included 14 systematic reviews of case-control studies comparing individuals with a radiographic diagnosis of all OA types and healthy controls, all submitted to the genetic examination of different polymorphisms in candidate genes. Meta-analyses showed a protective effect against knee and hand OA associated with GDF-5 gene (odds ratio [OR] 0.90, 95% confidence interval (CI) 0.85-0.95), and knee OA with ESRα gene (OR 0.63, 95% CI 1.26-1.97). SMAD3 gene was associated with knee and hip OA risk (OR 1.21. 95% CI 1.07-1.38) and MMP-1 gene was associated with temporomandibular OA (OR 1.58. 95% CI 1.26-1.97). CONCLUSION: Based on low-quality to critically-low-quality systematic reviews, some gene polymorphisms seem to be associated with risk or protection for OA. Further high-quality studies are needed to validate these hypotheses, contribute to disease understanding, and possibly help the decision-making related to early diagnosis and treatment options for OA. PROSPERO register CRD42021234231.
Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/genética , Osteoartrite do Joelho/diagnóstico , Polimorfismo Genético , Revisões Sistemáticas como AssuntoRESUMO
Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.
Assuntos
Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/genética , Alopecia/genética , Cerebelo/anormalidades , Anormalidades Craniofaciais/tratamento farmacológico , Anormalidades Craniofaciais/genética , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/genética , Misoprostol/uso terapêutico , Síndromes Neurocutâneas/tratamento farmacológico , Síndromes Neurocutâneas/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Alopecia/diagnóstico por imagem , Alopecia/tratamento farmacológico , Alopecia/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Feminino , Transtornos do Crescimento/diagnóstico por imagem , Transtornos do Crescimento/patologia , Humanos , Imageamento por Ressonância Magnética , Síndromes Neurocutâneas/diagnóstico por imagem , Síndromes Neurocutâneas/patologia , Fenótipo , Rombencéfalo/diagnóstico por imagem , Rombencéfalo/patologia , Nervo Trigêmeo/diagnóstico por imagem , Nervo Trigêmeo/efeitos dos fármacos , Nervo Trigêmeo/patologiaRESUMO
Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.
Assuntos
Anormalidades Múltiplas/genética , Encefalopatias/genética , Anormalidades Congênitas/genética , Retardo do Crescimento Fetal/genética , Ictiose/genética , Deformidades Congênitas dos Membros/genética , Microcefalia/genética , Fosfoglicerato Desidrogenase/genética , Natimorto/genética , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Encefalopatias/mortalidade , Encefalopatias/patologia , Brasil/epidemiologia , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/patologia , Consanguinidade , Feminino , Retardo do Crescimento Fetal/mortalidade , Retardo do Crescimento Fetal/patologia , Genes Letais/genética , Predisposição Genética para Doença , Humanos , Ictiose/mortalidade , Ictiose/patologia , Deformidades Congênitas dos Membros/mortalidade , Deformidades Congênitas dos Membros/patologia , Microcefalia/mortalidade , Microcefalia/patologia , Mutação de Sentido Incorreto/genética , Gravidez , Natimorto/epidemiologiaRESUMO
Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.
Assuntos
Anormalidades Múltiplas/genética , Manchas Café com Leite/genética , Deleção Cromossômica , Cromossomos Humanos Par 21/ultraestrutura , Face/anormalidades , Hipertonia Muscular/genética , Cromossomos Humanos Par 21/genética , Deficiências do Desenvolvimento/genética , Feminino , Perda Auditiva Bilateral/genética , Humanos , Recém-Nascido , Cariotipagem , Fenótipo , Escoliose/genéticaRESUMO
In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.
Assuntos
Surtos de Doenças , Doenças Fetais/epidemiologia , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Anticorpos Antivirais/líquido cefalorraquidiano , Encéfalo/anormalidades , Encéfalo/virologia , Brasil/epidemiologia , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/patologia , Feto , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Lactente , Microcefalia/complicações , Microcefalia/diagnóstico por imagem , Microcefalia/patologia , Neuroimagem , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/patologia , Síndrome , Zika virus/crescimento & desenvolvimento , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico por imagem , Infecção por Zika virus/patologiaRESUMO
In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.
Assuntos
Microcefalia/epidemiologia , Microcefalia/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Brasil/epidemiologia , Feminino , Humanos , Recém-Nascido , GravidezAssuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Predisposição Genética para Doença , Variação Genética , Esquizofrenia/genética , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/epidemiologia , Adulto JovemRESUMO
Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.
Assuntos
Aberrações Cromossômicas , Deleção Cromossômica , Cromossomos Humanos Par 22 , Ecocardiografia , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Ultrassonografia Pré-Natal , Aneuploidia , Brasil , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Gravidez , Estudos ProspectivosRESUMO
The aim of this study was to improve the completion of item 34 on birth certificates at four maternity hospitals in the city of São Paulo, Brazil, in the year 2008. The database of the Municipal Health Department's Information System on Live Births was used to monitor trends in reporting birth defects. An electronic web-based medical record was used to refer indeterminate cases to a leading medical genetics referral center. The electronic medical record contained the patient history, physical examination, and photographs of the newborn. Four maternity hospitals were assessed, with a total of 10,000 births during the year. None of the four hospitals had a staff geneticist. According to the Information System on Live Births, there was an increase in the number of birth defects reported by the four maternity hospitals when compared to previous years and to records for the city of São Paulo as a whole. Based on the findings, the web-based referral and counter-referral method proved efficient.
Assuntos
Declaração de Nascimento , Anormalidades Congênitas/epidemiologia , Notificação de Doenças/métodos , Internet/estatística & dados numéricos , Nascido Vivo/epidemiologia , Sistemas Computadorizados de Registros Médicos/estatística & dados numéricos , Brasil/epidemiologia , Maternidades/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , Recém-NascidoRESUMO
O objetivo foi aumentar a frequencia da notificacao de anomalias congenitas no campo 34 da Declaracao de Nascido Vivo em quatro maternidades do Municipio de Sao Paulo, Brasil, ao longo do ano de 2008. Utilizamos o banco de dados do Sistema de Informacoes sobre Nascidos Vivos da Secretaria Municipal de Saude de Sao Paulo para acompanhar a evolucao dos registros dos defeitos congenitos. Mediante prontuario eletronico, via Internet, os casos suspeitos eram enviados para um centro de referencia em genetica medica. O prontuario eletronico contem anamnese, exame fisico e fotos do recem-nascido. O estudo ocorreu em quatro maternidades com uma amostra total de 10 mil nascimentos no ano e que nao apresentam medico geneticista. Houve aumento da notificacao dos defeitos congenitos nas quatro maternidades onde o estudo foi realizado quando comparado com os anos anteriores e com o registro do Municipio de Sao Paulo. O metodo de referencia e contra-referencia utilizando a Internet mostrou-se eficaz.
The aim of this study was to improve the completion of item 34 on birth certificates at four maternity hospitals in the city of Sao Paulo, Brazil, in the year 2008. The database of the Municipal Health Department's Information System on Live Births was used to monitor trends in reporting birth defects. An electronic web-based medical record was used to refer indeterminate cases to a leading medical genetics referral center. The electronic medical record contained the patient history, physical examination, and photographs of the newborn. Four maternity hospitals were assessed, with a total of 10,000 births during the year. None of the four hospitals had a staff geneticist. According to the Information System on Live Births, there was an increase in the number of birth defects reported by the four maternity hospitals when compared to previous years and to records for the city of Sao Paulo as a whole. Based on the findings, the web-based referral and counter-referral method proved efficient.