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.
Inherited epidermolysis bullosa is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minimal trauma. Epidermolysis bullosa is ...clinically and genetically very heterogeneous, being classified into four main types according to the layer of skin in which blistering occurs: epidermolysis bullosa simplex (intraepidermal), junctional epidermolysis bullosa (within the lamina lucida of the basement membrane), dystrophic epidermolysis bullosa (below the basement membrane), and Kindler epidermolysis bullosa (mixed skin cleavage pattern). Furthermore, epidermolysis bullosa is stratified into several subtypes, which consider the clinical characteristics, the distribution of the blisters, and the severity of cutaneous and extracutaneous signs. Pathogenic variants in at least 16 genes that encode proteins essential for the integrity and adhesion of skin layers have already been associated with different subtypes of epidermolysis bullosa. The marked heterogeneity of the disease, which includes phenotypes with a broad spectrum of severity and many causal genes, hinders its classification and diagnosis. For this reason, dermatologists and geneticists regularly review and update the classification criteria. This review aimed to update the state of the art on inherited epidermolysis bullosa, with a special focus on the associated clinical and genetic aspects, presenting data from the most recent reclassification consensus, published in 2020.
Rare genetic disorders are currently in the spotlight due to the elevated number of different conditions and significant total number of affected patients. The study of these disorders is extremely ...helpful for the elucidation of physiological processes related with complex disorders. Isolated populations are instrumental for the study of genetic disorders, considering their homogeneity and high proportion of affected patients in a small geographic area. These favorable conditions lead to the creation of a new discipline, known as "population medical genetics", which integrates medical genetics, population genetics, epidemiological genetics and community genetics. In order to develop practical activities in this new discipline, the National Institute of Population Medical Genetics (INaGeMP) was created in 2008 in Brazil. INaGeMP has developed several tools and funded numerous research activities. In this review, we highlight three successful projects developed in the first 10 years of INaGeMP activities (2008-2018): a newborn screening pilot study for MPS VI in Northeast Brazil, the study of Machado-Joseph disease in Brazilian families with Azorian ancestry, and the high twinning rate in a small town in southern Brazil. The results of these projects in terms of scientific output and contributions to the affected communities highlight the success and importance of INaGeMP.
The association between the virus prenatal infection by Zika virus (ZIKV) and central nervous system disorders has been well established and it has been described as the Congenital Syndrome ...Associated to the Zika Virus (CSZ). However, the neurological development in those patients is still an object of study. The main differential diagnosis is the Cytomegalovirus (CMV).
Describe the involvement of microcephalic patients affected by the congenital infection by the Zika Virus or CMV.
Data has been collected from microcephalic patients whose birth took place after 2016 and which also had the congenital infection confirmed or presumed. The researched data consists in: congenital infection, head circumference from birth, presence of epilepsy, treatment by mono or polytherapy, electroencephalographic patterns, neurological physical examination and evaluation of gross motor development.
21 microcephalic children have been included showing the following congenital infectious syndromes: 9 were affected by cytomegalovirus (43%), 6 by the Zika virus (29%) and 6 ones by presumed infection due to the Zika virus (29%). From those ones, 13 (62%) presented epilepsy diagnosis including generalized crises and 9 (69%) were in current use of polytherapy. All of them also showed disorganized and asymmetrical base rhythms. Concerning the epileptiform activity, 5 presented multifocal activity and 3 ones hypsarrhythmia. All of the patients went under neuroimaging: 12 (57%) of them presented calcifications and 5 (24%) hydrocephalus. On the neurological exam, 17% presented a decreased axial tone and an enlarged appendicular. Smaller head circumference children had greater motor impairment and severity in the epilepsy. There was no difference in the frequency of epilepsy between children with CSZ and CMV.
Epilepsy is confirmed as one of the most important complications of congenital infections by CSZ and CMV.
•The congenital infections are implicated in the development of epilepsy, changing in the neurologic physical exam and in motor development.•The microcephaly outbreak highlighted the importance of studies which could establish the relation between the microcephaly and cerebral involvement.•There have not been identified a significant difference when comparing the manifestations in neither the epilepsy profile nor in the electroencephalographic characteristics in patients with CSZ and CMV, probably due to the fact that both the pathogens are causative of microcephaly.
To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011.
In this retrospective study, patients were identified through a national ...reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review.
Eighty-three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range IQR, 0.57–7). Median age at onset of symptoms was 10 days (IQR 5–30), whereas median age at diagnosis was 60 days (IQR 29–240, p=0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n=12) and without (n=71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay.
In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country.
Caracterizar uma amostra de pacientes brasileiros com a doença da urina de xarope de bordo (DXB) diagnosticados entre 1992 e 2011.
Neste estudo retrospectivo, os pacientes foram identificados por meio de um laboratório de referência nacional para o diagnóstico de DXB e por meio do contato com outros serviços de genética médica no Brasil. Os dados foram coletados por meio de uma revisão de prontuários.
83 pacientes de 75 famílias foram incluídos no estudo (idade média: 3 anos; intervalo interquartil (IQR): 0,57-7). A idade média no surgimento dos sintomas era de 10 dias (IQR: 5-30), ao passo que a idade média no diagnóstico era de 60 dias (IQR: 29-240; p=0,001). Somente três (3,6%) pacientes foram diagnosticados antes do surgimento de manifestações clínicas. Uma comparação entre pacientes com (n=12) e sem (n=71) um diagnóstico precoce mostra que o diagnóstico precoce está associado à presença de histórico familiar positivo e à redução na prevalência de manifestações clínicas no momento do diagnóstico, porém sem melhor resultado. Em geral, 98,8% dos pacientes têm algum atraso no desenvolvimento psicomotor ou neurológico.
No Brasil, os pacientes com DXB normalmente recebem um diagnóstico tardio e exibem um envolvimento neurológico e baixa sobrevivência, mesmo com um diagnóstico precoce. Sugerimos que políticas públicas específicas para o diagnóstico e tratamento da DXB sejam desenvolvidas e implementadas no país.
Longitudinal studies have consistently reported that prenatal exposure to acetaminophen can to lead to an increased risk of attention deficit-hyperactivity disorder during childhood. This study aimed ...to investigate the association between intrauterine exposure to acetaminophen and the presence of emotional and behavioral problems at the ages of 6 and 11 years in a low-middle income country.
We performed a prospective longitudinal population-based study using data from the 2004 Pelotas birth cohort. From the 4231 initial cohort participants, 3722 and 3566 children were assessed at 6 and 11 years of age, respectively. The outcomes were assessed using the parent version of Strengths and Difficulties Questionnaire (SDQ). The cut-off points established for the Brazilian population were used to categorize the outcomes. Crude and adjusted odds ratio were obtained through logistic regression.
Acetaminophen was used by 27.5% (95% confidence interval CI: 26.1-28.9) of the mothers at least once during pregnancy. The prevalence of emotional problems at 6 and 11 years was 13.6 and 19.9%, respectively. For hyperactivity problems, prevalence was 13.9 and 16.1%, respectively. Intrauterine exposure to acetaminophen increased the odds of having emotional (odds ratio OR = 1.47; 95% CI: 1.07-2.02) and hyperactivity/inattention (OR = 1.42; 95% CI: 1.06-1.92) problems in 6-year-old boys. At the age of 11, a small decrease in the effect was observed for both outcomes after adjustment: OR = 1.31 (95% CI: 0.99-1.73) for emotional problems and OR = 1.25 (95% CI: 0.95-1.65) for hyperactivity/inattention in boys. No association for any phenotypes at both ages was observed for girls.
The effect of intrauterine exposure to acetaminophen in emotional and hyperactivity symptoms was dependent on sex in a Brazilian cohort. While it seemed to be important for boys, mainly at 6 years of age, for girls, no association was observed.
HLA diversity in Brazil Boquett, Juliano A.; Bisso‐Machado, Rafael; Zagonel‐Oliveira, Marcelo ...
HLA : immune response genetics,
January 2020, 2020-01-00, Volume:
95, Issue:
1
Journal Article
Peer reviewed
Brazil is the fifth largest country in the world in area and the fifth most populous. The Brazilian voluntary Bone Marrow Donor Registry is the third largest in terms of number of donors in the ...world, being a valuable source of HLA genetics to characterize the donor population of Brazil as well. The genetic background of the Brazilian population is quite heterogeneous, resulting from 5 centuries of admixture among Native Americans, Europeans and Africans, making the Brazilian population unique in terms of genetic ancestry. The unique characteristics of populations in different Brazilian regions make them an exciting focus for genetic diversity studies. Studies on HLA genetic diversity of Brazilian populations have been conducted since the late 1980s and, in this review, we highlight the main findings from studies carried out in Brazil based on classical HLA. In addition, we calculated the genetic distance from the molecular data of the studies included in this review in order to have a broader view of the HLA diversity in Brazilian populations. We emphasize that characterization of HLA diversity is not only important for transplantation programs, but can shed a light on ancestry, history and other demographic patterns with or without association with autoimmune disease.
Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the ...sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018.
In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls.
The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.
New cases of thalidomide embryopathy in Brazil Schuler‐Faccini, Lavinia; Soares, Rosa Castalia Franca; de Sousa, Artur Custodio Moreira ...
Birth defects research. A Clinical and molecular teratology,
September 2007, Volume:
79, Issue:
9
Journal Article
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