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1.
Arq Neuropsiquiatr ; 78(7): 403-411, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32627805

RESUMO

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.


Assuntos
Microcefalia/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Encéfalo , Cefalometria , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Microcefalia/diagnóstico , Destreza Motora , Gravidez , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito
2.
Rev Fac Cien Med Univ Nac Cordoba ; 77(2): 100-105, 2020 04 07.
Artigo em Espanhol | MEDLINE | ID: mdl-32558512

RESUMO

Introduction: Microcephaly and brain abnormalities may be due to multiple etiologies, one of them is the congenital infection by Zika virus (ZIKV). From 2016 to the present, there has been a series of ZIKV outbreaks in Argentina. Methods: National Network of Congenital Anomalies (RENAC) and the National Institute of Viral Diseases (INEVH), under the National Administration of Laboratories and Health Institutes "Carlos Malbrán" (ANLIS), carry out the intensified surveillance of newborns with microcephaly and brain abnormalities. This article presents the clinical characteristics and laboratory testof patients detected with congenital infection by ZIKV between April 2016 to March 2018, Results: 10 cases with embryopathy were detected, six autochthonous and four imported; in two cases, the mothers were asymptomatic during pregnancy; all the cases presented microcephaly and cranial facial disproportion, ventriculomegaly in seven cases and in six cerebral calcifications. The diagnosis of congenital infection by Zika in the newborn was made by antigen-specific Immunoglobulin M (MAC-ELISA) and plaque-reduction neutralization test (PRNT90 ). PCR was negative in all cases. Conclusion: the patients presented clinical features that were consistent with those reported in other countries. The need for serological studies that allow confirmation is emphasized, ruling out cross-reactivity with other Flaviviruses.


Assuntos
Microcefalia/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Argentina/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia
3.
Medicine (Baltimore) ; 99(16): e19813, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311999

RESUMO

RATIONALE: Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene, which was not reported before. Our study increases the cohort of Chinese WDSTS patients, and expand the WDSTS phenotypic and variation spectrum. PATIENT CONCERNS: The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, besides he had congenital heart disease (ventricular septal defects), strabismus, hypotonia, amblyopia, delayed speech and language development, delayed psychomotor development, and amblyopia (HP:0000646) which was not reported before. DIAGNOSIS: FOXL2 gene was cloned and sequenced, however, there was no mutation detected in this patient. The result of Chromosomal microarray analysis was normal. The patient was diagnosed as WDSTS by whole exome sequencing. INTERVENTIONS: The patient received cardiac surgery, frontalis suspension and regular speech and occupational therapy. He also treated with growth hormone (GH). OUTCOMES: The patient's symptoms are improved after cardiac surgery and frontalis suspension, he can express himself well now and had a 10 cm gain in height. LESSONS: As the relationship between genotype and phenotype becomes more and more clear, WES is incredibly powerful tool to diagnose the disease of WDSTS.


Assuntos
Anormalidades Múltiplas/genética , Blefarofimose/diagnóstico , Contratura/genética , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Cardiopatias Congênitas/diagnóstico , Histona-Lisina N-Metiltransferase/genética , Hipertricose/congênito , Deficiência Intelectual/genética , Microcefalia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Anormalidades da Pele/diagnóstico , Anormalidades Urogenitais/diagnóstico , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/terapia , Grupo com Ancestrais do Continente Asiático/genética , Criança , Contratura/diagnóstico , Contratura/terapia , Erros de Diagnóstico , Facies , Genótipo , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/terapia , Hormônio do Crescimento/uso terapêutico , Cardiopatias Congênitas/cirurgia , Humanos , Hipertricose/diagnóstico , Hipertricose/etiologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/terapia , Masculino , Microcefalia/diagnóstico , Microcefalia/terapia , Mutação , Fenótipo , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
4.
Acta Trop ; 206: 105438, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32165128

RESUMO

INTRODUCTION: Typical symptoms of primary Zika virus infection are not specific and share similarities with other arbovirus infections such as dengue fever and chikungunya. As acute infection can be asymptomatic in up to 73% of cases, infants with microcephaly represent a diagnostic challenge for pediatricians. We describe the frequency of congenital Zika syndrome (CZS) in Brazilian children born to asymptomatic pregnant mothers and its differential diagnosis. METHODS: This longitudinal, observational study was conducted on children with suspected CZS whose mothers did not report rash during pregnancy, referred to the reference hospital in a metropolitan area of ​ Rio de Janeiro, Brazil. The diagnosis of suspected CZS was based on Brazilian Ministry of Health protocol. RESULTS: Forty-three (17%) of 246 referred children were born to mothers without rash history during pregnancy. Thirteen (30%) of 43 children met the Brazilian Ministry of Health criteria for CZS, all with microcephaly (two post-natal). The other children included 11 cases with post-natal microcephaly due to hypoxic-ischemic encephalopathy (6), non-progressive encephalopathy of unknown etiology (2), microcephaly under investigation (2) and congenital toxoplasmosis (1); 17 children were misdiagnosed with microcephaly and progressed with normal head circumference during the follow-up period; one child was included because of epidemiological link and one was loss to follow-up. All children who underwent laboratory investigation for ZIKV infection during neonatal period had negative RT-qPCR tests. CONCLUSION: We emphasize the increasing importance of CZS in differential diagnosis of microcephaly at birth or post-natal period. Detailed clinical investigation assisted by neuroimaging tests may clarify the diagnosis of CZS when laboratory tests are not available during the acute phase of the disease.


Assuntos
Microcefalia/diagnóstico , Complicações Infecciosas na Gravidez , Infecção por Zika virus/congênito , Infecção por Zika virus/diagnóstico , Adulto , Infecções Assintomáticas , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Estudos Longitudinais , Gravidez
5.
Clin Dysmorphol ; 29(2): 97-100, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31929334

RESUMO

Deletion of the 1q43q44 chromosomal region has been related to a clinical syndrome characterized by neurodevelopmental delay, intellectual disability, microcephaly, congenital abnormality of the corpus callosum, and epilepsy and dysmorphic features. A wide variability of the clinical features have been linked to the contiguous deleted genes and incomplete penetrance has been observed too. Here, we report a 4-years-old boy with microcephaly, neurodevelopmental delay, and cardiac atrial septal defect, who had a de-novo 117 Kb 1q43-q44 microdeletion. The deleted chromosomal region encompassed the two genes SDCCAG8 and AKT3. The characteristics of the deletion and the clinical condition of the patient suggest a pathogenic role of the 1q43-q44 deletion, supporting a pivotal role of AKT3 gene in the expression of the clinical phenotype.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 1 , Haploinsuficiência/genética , Microcefalia/diagnóstico , Microcefalia/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/genética , Pré-Escolar , Hibridização Genômica Comparativa , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino
6.
Int J Gynaecol Obstet ; 148 Suppl 2: 29-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975397

RESUMO

OBJECTIVE: To explore the perceptions and experiences of pregnant women in accessing healthcare services during the epidemic in Colombia during 2015-2016. METHODS: A qualitative study using semistructured interviews was conducted in Villavicencio. Six women who had been diagnosed with Zika virus infection during their pregnancies and whose fetus had suspected microcephaly participated in the investigation. Grounded theory was used and thematic content analysis was made for each category identified. RESULTS: Three main themes affecting access to healthcare services were identified: (1) women knew basic information about the virus, but it was limited; (2) access to services was delayed due to their lack of availability or limited supply in the municipality; and (3) most of the participants made out-of-pocket payments to get access to services that were not provided. CONCLUSIONS: Several gaps were identified in the provision of healthcare services to pregnant women during the Zika epidemic. Policy makers need to utilize the results from affected communities to develop and implement public policies that adapt and respond to their priorities and needs.


Assuntos
Acesso aos Serviços de Saúde/normas , Complicações Infecciosas na Gravidez/terapia , Infecção por Zika virus/terapia , Adulto , Colômbia , Epidemias , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/virologia , Teoria Fundamentada , Acesso aos Serviços de Saúde/economia , Humanos , Recém-Nascido , Microcefalia/diagnóstico , Microcefalia/virologia , Determinação de Necessidades de Cuidados de Saúde , Gravidez , Pesquisa Qualitativa , Zika virus , Infecção por Zika virus/transmissão
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1203-1205, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31813148

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus featuring increased nuchal thickness. METHODS: Routine G-banding karyotyping and single nucleotide polymrophism array were carried out to detect genomic copy number variations (CNVs) in the fetus. RESULTS: The fetus was found to harbor a heterozygous 3.8 Mb deletion in the 2q22.2-q22.3 region encompassing the ZEB2 gene, which is closely associated with Mowat-Wilson syndrome (MWS). CONCLUSION: Haploinsufficiency of the ZEB2 gene may predispose to MWS. Lack of knowledge regarding to the ultrasonographic features of MWS may lead to misdiagnosis of the syndrome.


Assuntos
Variações do Número de Cópias de DNA , Doença de Hirschsprung/diagnóstico , Deficiência Intelectual/diagnóstico , Microcefalia/diagnóstico , Facies , Feminino , Feto , Doença de Hirschsprung/genética , Humanos , Deficiência Intelectual/genética , Microcefalia/genética , Gravidez , Diagnóstico Pré-Natal , Deleção de Sequência , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
8.
Ophthalmic Surg Lasers Imaging Retina ; 50(12): 779-784, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877223

RESUMO

BACKGROUND AND OBJECTIVE: Antenatal Zika virus (ZIKV) or toxoplasmosis infections may present with isolated eye abnormalities with absence of other apparent birth defects. The purpose of this article is to discuss the overlapping spectrum of clinical presentation and retinochoroidal scarring in congenital ZIKV and toxoplasmosis infections. PATIENTS AND METHODS: Prenatal ultrasound abnormalities seen from antenatal ZIKV and toxoplasmosis infections overlap and may include intracranial calcifications, microcephaly, and intrauterine growth restriction. The clinical spectrum of both infections in less severely affected infants and children may include nonspecific neurological impairment such as developmental delay and seizures. RESULTS: Inherent limitations in serological testing pose additional barriers in establishing a diagnosis. Retinal pigment epithelium (RPE) mottling in ZIKV infection can occur in isolation or adjacent to retinochoroidal atrophy. In contrast, RPE mottling outside of the borders of retinochoroidal atrophy is not typically seen in toxoplasmosis. To date, postnatal reactivation of congenital eye lesions as seen in toxoplasmosis have not been reported with ZIKV infection. CONCLUSIONS: As children infected with congenital ZIKV grow older, subclinical eye abnormalities may be indistinguishable from toxoplasmosis. Brazil has had high prevalence of both diseases with long-term information available on toxoplasmosis only. Surveillance guidelines for asymptomatic eye abnormalities will likely evolve. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:779-784.].


Assuntos
Coriorretinite/diagnóstico , Cicatriz/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Virais/diagnóstico , Complicações Infecciosas na Gravidez , Toxoplasmose Congênita/complicações , Infecção por Zika virus/complicações , Pré-Escolar , Coriorretinite/etiologia , Cicatriz/etiologia , Infecções Oculares Parasitárias/etiologia , Infecções Oculares Virais/etiologia , Feminino , Humanos , Lactente , Microcefalia/diagnóstico , Gravidez , Infecção por Zika virus/congênito
9.
Epileptic Disord ; 21(5): 466-470, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31617495

RESUMO

Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the asparagine synthetase gene. It is characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. A decrease in asparagine in CSF or plasma guides subsequent investigations in some cases, but normal values are described in other cases. Therefore, reaching a diagnosis is challenging and relies on exome sequencing. We report the case of a child with progressive microcephaly, irritability, startle reflexes, and jitteriness since birth. Focal clonic and myoclonic seizures, status epilepticus, and infantile spasms appeared in the first months of life. At first, the EEG showed multifocal epileptic activity which later turned into modified hypsarrhythmia and discontinuous activity. Brain MRI showed brain atrophy, a simplified gyral pattern, and poor myelination. Plasma asparagine levels were normal. Due to remote parental consanguinity, a study of contiguous regions of runs of homozygosity was performed, showing a 5-Mb region (chr7:95629078-100679007) including the asparagine synthetase gene. The molecular analysis of this gene led to identification of a novel homozygous missense mutation, c.761G>T(p.Gly254Val), in our patient. The peculiar electroclinical phenotype may lead to diagnostic suspicion and molecular analysis which may benefit genetic counselling. [Published with video sequence].


Assuntos
Aspartato-Amônia Ligase/deficiência , Encefalopatias/fisiopatologia , Deficiência Intelectual/fisiopatologia , Microcefalia/fisiopatologia , Atrofia/diagnóstico , Atrofia/fisiopatologia , Encefalopatias/diagnóstico , Encefalopatias/genética , Eletroencefalografia/métodos , Humanos , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Convulsões/genética , Convulsões/fisiopatologia
10.
Mol Med Rep ; 20(6): 5145-5151, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638258

RESUMO

To the best of our knowledge, the present study reported the case of the first Chinese patient with microcephaly­capillary malformation (MIC­CAP) syndrome caused by a novel compound heterozygous mutation in the STAMBP gene, which encodes STAM binding protein. The present study also provides a review of relevant previously published studies. A boy with MIC­CAP syndrome with developmental delay, intractable epilepsy and prominent dyskinesia was examined. A pathogenic mutation was identified by whole­exome sequencing, and the protein structure and function affected by this mutation were predicted using bioinformatics analysis. Finally, the clinical features of 16 other cases reported in previous studies were reviewed and compared. A novel compound heterozygous mutation of the STAMBP (c.1119­1G>T, c.968A>G) was identified in the present study and epilepsy was refractory, consistent with previously reported cases. The present study also highlighted the fact that STAMBP mutation­associated MIC­CAP often presents as intractable early­life epilepsy, which may lead to mortality.


Assuntos
Capilares/anormalidades , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Epilepsia/genética , Predisposição Genética para Doença , Microcefalia/genética , Mutação , Ubiquitina Tiolesterase/genética , Malformações Vasculares/genética , Idade de Início , Criança , Análise Mutacional de DNA , Epilepsia/diagnóstico , Estudos de Associação Genética , Humanos , Masculino , Microcefalia/diagnóstico , Linhagem , Análise de Sequência de DNA , Síndrome , Malformações Vasculares/diagnóstico
12.
Arch Gynecol Obstet ; 300(5): 1211-1219, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31493089

RESUMO

PURPOSE: To evaluate which reference curve (RC)-Snijders, Intergrowth 21st (IG21) and World Health Organization (WHO)-is more accurate for microcephaly diagnosis. METHODS: Retrospective cohort study with more than 30,000 exams in more than 11,000 women. Microcephaly was confirmed by a neonatologist at birth and positive predictive values (PPVs) and misdiagnosis were assessed. RESULTS: A total of 71 cases were confirmed as microcephaly at birth. IG21 and Snijders PPVs showed to be more significant over WHO's (p < 0.001), without difference between them (p = 0.39). All RC were superimposed and did not show significant difference. When evaluated in different fragments, three trends were observed (until 30 weeks, between 30 and 36 and after 36 weeks of gestational age), with the latter interval showing a significant difference between IG21 and WHO (p = 0.0079). Conversely, WHO exhibited only one misdiagnosis, a much lower rate than Snijders, who missed eight cases and IG21, nine. CONCLUSION: WHO's RC appears to misdiagnose fewer cases, which could be useful for a population screening, while IG21's RC presented a more significant PPV, being more useful for a more precise final diagnosis in reference centers.


Assuntos
Microcefalia/diagnóstico por imagem , Microcefalia/diagnóstico , Ultrassonografia Pré-Natal/métodos , Organização Mundial da Saúde/organização & administração , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto Jovem
13.
PLoS One ; 14(9): e0222291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527883

RESUMO

Interception of potential invasive species at ports-of-entry is essential for effective biosecurity and biosurveillance programs. However, taxonomic assessment of the immature stages of most arthropods is challenging; characters for identification are often dependent on adult morphology and reproductive structures. This study aims to strengthen the identification of such specimens through DNA barcoding, with a focus on microlepidoptera. A sample of 241 primarily immature microlepidoptera specimens intercepted at U.S. ports-of-entry from 2007 to 2011 were selected for analysis. From this sample, 201 COI-5P sequences were generated and analyzed for concordance between morphology-based and DNA-based identifications. The retrospective analysis of the data over 10 years (2009 to 2019) using the Barcode of Life Data (BOLD) system demonstrates the importance of establishing and growing DNA barcode reference libraries for use in specimen identification. Additionally, analysis of specimen identification using public data (43.3% specimens identified) vs. non-public data (78.6% specimens identified) highlights the need to encourage researchers to make data publicly accessible. DNA barcoding surpassed morphological identification with 42.3% (public) and 66.7% (non-public) of the sampled specimens achieving a species-level identification, compared to 38.3% species-level identification by morphology. Whilst DNA barcoding was not able to identify all specimens in our dataset, its incorporation into border security programs as an adjunct to morphological identification can provide secondary lines of evidence and lower taxonomic resolution in many cases. Furthermore, with increased globalization, database records need to be clearly annotated for suspected specimen origin versus interception location.


Assuntos
Artrópodes/genética , Controle de Pragas/métodos , Animais , DNA/genética , Código de Barras de DNA Taxonômico/métodos , Humanos , Microcefalia/diagnóstico , Microcefalia/parasitologia , Estudos Retrospectivos
14.
BMJ Case Rep ; 12(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31413053

RESUMO

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare condition that causes abnormalities of the head and face. Other major extracranial malformations may also be found. The authors present a case of an MFDM in a 35 weeks newborn with antenatal growth restriction. The patient required resuscitation at birth and was diagnosed with oesophageal atresia with tracheoesophageal fistula at day 1. At physical examination he presented multiple congenital malformations including prominent forehead, plagiocephaly, low-set ears, malformed auricles, hypertelorism, downward-slanting eyes, micrognathia, everted lower lip, short neck, wide-spaced nipples and inguinal hernia. Imaging investigation showed dysplasia of the inner ear with agenesis of the vestibular-cochlear nerves and global cerebral atrophy. Analysis of the EFTUD2 gene revealed that the patient was a heterozygous carrier of a pathogenic mutation (c.831_832del[p.Lys277Asnsf*7]), which has not been previously described. This case illustrates the challenges faced in diagnosing and treating MFDM patients.


Assuntos
Atresia Esofágica/diagnóstico , Disostose Mandibulofacial/diagnóstico , Microcefalia/diagnóstico , Anormalidades Múltiplas , Diagnóstico Diferencial , Atresia Esofágica/complicações , Atresia Esofágica/diagnóstico por imagem , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imagem por Ressonância Magnética , Masculino , Disostose Mandibulofacial/complicações , Disostose Mandibulofacial/diagnóstico por imagem , Disostose Mandibulofacial/genética , Microcefalia/complicações , Microcefalia/diagnóstico por imagem , Microcefalia/genética , Fatores de Alongamento de Peptídeos/genética , Ribonucleoproteína Nuclear Pequena U5/genética , Síndrome
15.
J. pediatr. (Rio J.) ; 95(4): 466-474, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040346

RESUMO

Abstract Objectives: To describe aspects of the microcephaly epidemic in the state of Piauí. Methods: All cases of congenital microcephaly confirmed in the state between 2015 and 2016 were included (n = 100). Investigation forms of the Regional Reference Center for Microcephaly were reviewed. Discarded cases (n = 63) were used as a comparison group. Results: In October, November, and December 2015 incidence rates reached 4.46, 6.33 and 3.86/1000 live births, respectively; 44 cases were reported in the state capital. Among the mothers of confirmed and discarded cases, the frequency of skin rash during pregnancy was 50/97 (51.5%) and 8/51 (15.7%), respectively (p < 0.001); 33 confirmed cases (35.9%) had a head circumference z-score between −2 and −3, 23 (25%) between −3 and −4, and 8 (8.7%) had a z-score of less than −4. Head computer tomography scans revealed calcifications in 78/95 (82.1%) cases. Lissencephaly, hydrocephalus and agenesis of the corpus callosum were also frequently observed. Ophthalmic findings included retinal pigment epithelium rarefaction and atrophy. Absence of otoacoustic emissions was observed in 21/70 cases. One newborn also presented lower limb muscle atrophy. There were no significant differences in vaccination rates for influenza, diphtheria-tetanus-acellular pertussis, and hepatitis B in either group. Conclusions: The state of Piauí, like others in the northeastern region, faced an epidemic of congenital microcephaly between 2015 and 2016, presumably related to congenital Zika virus infection, more intense in the capital. Current challenges include the improvement of vector control, basic research, scaling-up of diagnostic tools for pre-natal screening of Zika virus, vaccines, and health care for affected children.


Resumo Objetivos: Descrever os aspectos da epidemia de microcefalia no Estado do Piauí. Métodos: Foram incluídos todos os casos de microcefalia congênita confirmados no estado entre 2015-2016 (n = 100). Os formulários de investigação do Centro Regional de Referência em Microcefalia foram analisados. Os casos descartados (n = 63) foram usados como grupo de comparação. Resultados: Em outubro, novembro e dezembro de 2015, as taxas de incidência atingiram 4,46, 6,33 e 3,86/1.000 nascidos vivos, respectivamente; 44 casos foram relatados na capital do estado. Entre as mães de casos confirmados e descartados, a frequência de erupção cutânea durante a gravidez foi 50/97 (51,5%) e 8/51 (15,7%), respectivamente (p < 0,001); 33 casos confirmados (35,9%) apresentaram um escore z de perímetro cefálico entre -2 e -3, 23 (25%) entre -3 e -4 e 8 (8,7%) apresentaram escore z inferior a -4. As tomografias computadorizadas cerebrais revelaram calcificações em 78/95 (82,1%) dos casos. Lisencefalia, hidrocefalia e agenesia do corpo caloso também foram observadas com mais frequência. Os achados oftalmológicos incluíram rarefação e atrofia do epitélio pigmentar da retina. Foram observadas ausência de emissões otoacústicas em 21/70 casos. Um recém-nascido também apresentou atrofia muscular dos membros inferiores. Não houve diferenças significativas nas taxas de vacinação para gripe, vacina difteria tétano e coqueluche acelular e hepatite B em qualquer grupo. Conclusões: O Estado do Piauí, como outros na região Nordeste, enfrentou, entre 2015 e 2016, uma epidemia de microcefalia congênita, supostamente relacionada à infecção congênita pelo vírus Zika, mais intensa na capital. Os desafios atuais incluem melhora do controle de vetores, pesquisa básica, ampliação de ferramentas de diagnóstico para exame pré-natal do vírus Zika, vacinas e cuidados de saúde para crianças afetadas.


Assuntos
Humanos , Gravidez , Adolescente , Adulto , Adulto Jovem , Complicações Infecciosas na Gravidez/epidemiologia , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Brasil/epidemiologia , Características de Residência , Cefalometria , Incidência , Surtos de Doenças , Idade Gestacional , Análise Espaço-Temporal , Zika virus/isolamento & purificação , Microcefalia/virologia
16.
Clin Dysmorphol ; 28(4): 175-183, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31162149

RESUMO

Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder caused by biallelic variants in UBE3B. Kaufman oculocerebrofacial syndrome is characterized by a recognizable pattern of malformations including moderate to severe intellectual disability, growth deficiency, microcephaly and a distinctive facial gestalt. Common craniofacial features include short upslanting palpebral fissures, blepharophimosis or ptosis, ear anomalies, hearing loss, palate anomalies and stridor/laryngomalacia. The aim of this study was to describe the phenotypic features and the genotype of five new individuals from three unrelated families, and to review systematically the published information of 26 cases. The main features are summarized contributing to further characterize the natural history of the disease. Novel phenotypic features and two novel pathogenic variants in UBE3B are reported: A splice site variant (c.2569-1G > C) and a nonsense variant (c.518C > A, p.Ser173Ter). Kaufman oculocerebrofacial syndrome is likely an underdiagnosed disorder which can be clinically recognized based on its distinctive facial gestalt and relatively homogenous natural history.


Assuntos
Anormalidades do Olho/diagnóstico , Deficiência Intelectual/diagnóstico , Deformidades Congênitas dos Membros/diagnóstico , Microcefalia/diagnóstico , Fenótipo , Pré-Escolar , Anormalidades do Olho/genética , Facies , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Deficiência Intelectual/genética , Deformidades Congênitas dos Membros/genética , Masculino , Microcefalia/genética , Mutação , Irmãos , Ubiquitina-Proteína Ligases/genética , Sequenciamento Completo do Genoma
17.
Am J Case Rep ; 20: 723-725, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31110169

RESUMO

BACKGROUND The Zika virus is an arbovirus that has as main source of transmission the bite of infected insects of the genus Aedes and has been associated with cases of congenital malformation and microcephaly in neonates. However, other sources of transmission have been identified since the emergence of this virus in the world population, such as vertical transmission by semen and possibly other body fluids such as vaginal secretion and breast milk. CASE REPORT An infant, born to a mother whose previous delivery was a baby with severe microcephaly, was normal and was negative for Zika virus at birth but developed secondary microcephaly 1 month later, that persisted. The baby was exclusively breast-fed and Zika virus was present in the mother's milk. CONCLUSIONS We report the detection of Zika virus exclusively in the breast milk of a woman after her second delivery of an infant, who later developed microcephaly. This case is consistent with possible vertical transmission.


Assuntos
Aleitamento Materno , Transmissão Vertical de Doença Infecciosa , Microcefalia/etiologia , Leite Humano , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/transmissão , Feminino , Humanos , Recém-Nascido , Microcefalia/diagnóstico
18.
Am J Ophthalmol ; 207: 87-98, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077665

RESUMO

PURPOSE: Familial exudative vitreoretinopathy (FEVR) is a rare finding in patients with genetic forms of microcephaly. This study documents the detailed phenotype and expands the range of genetic heterogeneity. DESIGN: Retrospective case series. METHODS: Twelve patients (10 families) with a diagnosis of FEVR and microcephaly were ascertained from pediatric genetic eye clinics and underwent full clinical assessment including retinal imaging. Molecular investigations included candidate gene Sanger sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). RESULTS: All patients had reduced vision and nystagmus. Six were legally blind. Two probands carried bi-allelic LRP5 variants, both presenting with bilateral retinal folds. A novel homozygous splice variant, and 2 missense variants were identified. Subsequent bone density measurement identified osteoporosis in one proband. Four families had heterozygous KIF11 variants. Two probands had a retinal fold in one eye and chorioretinal atrophy in the other; the other 2 had bilateral retinal folds. Four heterozygous variants were found, including 2 large deletions not identified on Sanger sequencing or WES. Finally, a family of 2 children with learning difficulties, abnormal peripheral retinal vasculogenesis, and rod-cone dystrophy were investigated. They were found to have bi-allelic splicing variants in TUBGCP6. Three families remain unsolved following WES and WGS. CONCLUSIONS: Molecular diagnosis has been achieved in 7 of 10 families investigated, including a previously unrecognized association with LRP5. WGS enabled molecular diagnosis in 3 families after prior negative Sanger sequencing of the causative gene. This has enabled patient-specific care with targeted investigations and accurate family counseling.


Assuntos
Anormalidades Múltiplas , Vitreorretinopatias Exsudativas Familiares/genética , Cinesina/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Microcefalia/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Adolescente , Criança , Pré-Escolar , DNA/genética , Análise Mutacional de DNA , Eletrorretinografia , Vitreorretinopatias Exsudativas Familiares/diagnóstico , Vitreorretinopatias Exsudativas Familiares/metabolismo , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Lactente , Cinesina/metabolismo , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Microcefalia/diagnóstico , Microcefalia/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Linhagem , Fenótipo , Estudos Retrospectivos , Tomografia de Coerência Óptica
19.
Pediatr Dev Pathol ; 22(6): 566-570, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30952201

RESUMO

Aicardi-Goutières syndrome (AGS) is a rare syndrome characterized by calcification, diffuse demyelination, and variable degree of brain atrophy. The syndrome is genetically heterogeneous with mutations in 7 genes, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1 (interferon-induced helicase c domain-containing protein 1) associated with the syndrome, so far. These mutations lead to the overproduction of α-interferon within the central nervous system. Mutations in IFIH1 have been recently described in a subset of AGS, with only 1 previous report of neuropathological findings. We report neuropathological findings in a second case of AGS with a known mutation in IFIH1 gene. The patient is a 16-year-old adolescent boy with early-onset symptoms that progressed to profound loss of cognitive and motor functions. The patient experienced sudden cardiopulmonary arrest at the age of 16 years. At autopsy, the cause of death was determined to be pulmonary thromboembolism. Neuropathological examination revealed microcephaly (brain weight: 916 g) with relatively mild brain atrophy on gross examination. Microscopic examination revealed multifocal calcifications limited to small to medium central nervous system arteries (no evidence of calcification in other organs), involving bilateral cerebral cortex, basal ganglia, thalamus, and cerebellum. Ultrastructural examination showed Calcospherules limited to the vessel walls and the perivasulcar area without evidence of neuronal ferrugination or tubuloreticular bodies. The extent of calcifications was variable across different brain regions, resembling findings in previously reported cases and correlated with the extent of IFIH1 protein expression (data derived from Allen Brain Institute). AGS is a rare cause of brain calcifications that can closely mimic congenital and neonatal infections such as Rubella and similar infections.


Assuntos
Doenças Autoimunes do Sistema Nervoso/patologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Helicase IFIH1 Induzida por Interferon/genética , Microcefalia/etiologia , Malformações do Sistema Nervoso/patologia , Calcificação Vascular/etiologia , Adolescente , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Evolução Fatal , Marcadores Genéticos , Humanos , Masculino , Microcefalia/diagnóstico , Microcefalia/patologia , Mutação , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/genética , Calcificação Vascular/diagnóstico , Calcificação Vascular/patologia
20.
BMC Nephrol ; 20(1): 126, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975089

RESUMO

BACKGROUND: Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies. WDR73 pathogenic variants were described as the first genetic cause of GAMOS and, very recently, four novel causative genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. CASE PRESENTATION: We present the clinical and genetic characteristics of two unrelated infants with clinical suspicion of GAMOS who were born from consanguineous parents. Both patients showed a similar clinical presentation, with early-onset nephrotic syndrome, microcephaly, brain atrophy, developmental delay, axial hypotonia, and early fatality. We identified two novel likely disease-causing variants in the OSGEP gene. These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants. CONCLUSIONS: Our findings expand the spectrum of pathogenic variants in the OSGEP gene and, taken in conjunction with the results of the literature review, suggest that the OSGEP gene should be considered the main known monogenic cause of GAMOS. Early genetic diagnosis of GAMOS is of paramount importance for genetic counseling and family planning.


Assuntos
Hérnia Hiatal , Rim/patologia , Metaloendopeptidases/genética , Microcefalia , Nefrose , Síndrome Nefrótica , Atrofia , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Deterioração Clínica , Evolução Fatal , Feminino , Predisposição Genética para Doença , Hérnia Hiatal/complicações , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/genética , Hérnia Hiatal/mortalidade , Homozigoto , Humanos , Lactente , Expectativa de Vida , Masculino , Microcefalia/complicações , Microcefalia/diagnóstico , Microcefalia/etiologia , Microcefalia/genética , Microcefalia/mortalidade , Nefrose/complicações , Nefrose/diagnóstico , Nefrose/genética , Nefrose/mortalidade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/genética
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