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1.
Clin Genet ; 98(3): 299-302, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32621286

RESUMO

Neural tube defects (NTD) are among the most common congenital anomalies, affecting about 1:1000 births. In most cases, the etiology of NTD is multifactorial and the genetic variants associated with them remain largely unknown. There is extensive evidence from animal models over the past two decades implicating SHROOM3 in neural tube formation; however, its exact role in human disease has remained elusive. In this report, we present the first case of a human fetus with a homozygous loss of function variant in SHROOM3. The fetus presents with anencephaly and cleft lip and palate, similar to previously described Shroom3 mouse mutants and is suggestive of a novel monogenic cause of NTD. Our case provides clarification on the contribution of SHROOM3 to human development after decades of model organism research.


Assuntos
Anencefalia/genética , Fenda Labial/genética , Fissura Palatina/genética , Proteínas dos Microfilamentos/genética , Anencefalia/complicações , Anencefalia/patologia , Fenda Labial/complicações , Fenda Labial/patologia , Fissura Palatina/complicações , Fissura Palatina/patologia , Feminino , Feto , Homozigoto , Humanos , Mutação com Perda de Função/genética , Análise em Microsséries , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia
2.
J Hum Genet ; 65(11): 985-993, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32576942

RESUMO

Neural tube defects (NTDs) are debilitating human congenital abnormalities due to failure of neural tube closure. Sonic Hedgehog (SHH) signaling is required for dorsal-ventral patterning of the neural tube. The loss of activation in SHH signaling normally causes holoprosencephaly while the loss of inhibition causes exencephaly due to failure in neural tube closure. WDR34 is a dynein intermedia chain component which is required for SHH activation. However, Wdr34 knockout mouse exhibit exencephaly. Here we screened mutations in WDR34 gene in 100 anencephaly patients of Chinese Han population. Compared to 1000 Genome Project data, two potentially disease causing missense mutations of WDR34 gene (c.1177G>A; p.G393S and c.1310A>G; p.Y437C) were identified in anencephaly patients. These two mutations did not affect the protein expression level of WDR34. Luciferase reporter and endogenous target gene expression level showed that both mutations are lose-of-function mutations in SHH signaling. Surprisingly, WDR34 could promote planar cell polarity (PCP) signaling and the G393S lost this promoting effect on PCP signaling. Morpholino knockdown of wdr34 in zebrafish caused severe convergent extension defects and pericardial abnormalities. The G393S mutant has less rescuing effects than both WT and Y437C WDR34 in zebrafish. Our results suggested that mutation in WDR34 could contribute to human NTDs by affecting both SHH and PCP signaling.


Assuntos
Anencefalia/genética , Proteínas de Transporte/genética , Proteínas Hedgehog/genética , Defeitos do Tubo Neural/genética , Adulto , Anencefalia/patologia , Animais , Polaridade Celular/genética , Anormalidades Congênitas/genética , Anormalidades Congênitas/patologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genoma Humano/genética , Humanos , Masculino , Defeitos do Tubo Neural/patologia , Adulto Jovem , Peixe-Zebra/genética
3.
Rom J Morphol Embryol ; 61(2): 335-343, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33544785

RESUMO

Anencephaly is a severe malformation of the central nervous system (CNS), being one of the most common types of neural tube defects. It is defined as total or partial absence of the calvarium, with absence of the brain. Anencephaly has an incidence of 1 to 5 in every 1000 births, and the mortality rate is 100% during intrauterine life or within hours or days after birth. The etiology of anencephaly remains unclear, but various maternal-related environmental and genetic risk factors have been reported, which include diabetes, obesity, exposure to different drugs or toxins, genetic polymorphisms and mutations, as well as positive family history for neural tube defects. One of the most important nutritional factors in the development of anencephaly is folate deficiency. Methylenetetrahydrofolate reductase (MTHFR) gene codes the enzyme involved in the intracellular metabolism of folic acid; the 677C-T polymorphism of this gene causes the thermolability of the enzyme and decreased enzymatic activity, which is also dependent of folate plasmatic level. Etiopathogenesis of anencephaly includes several mutations in various other genes, such as: platelet-derived growth factor receptor alpha (PDGFRA), cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1), Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation. Screening tests include maternal serum alpha-fetoprotein level and ultrasound (US) examination. During the first trimester US screening, anencephaly is now detected in all cases, but in order to decrease the complication rate of pregnancy termination, the diagnosis should be established as soon as possible, during the pregnancy confirmation US. We conclude that given that anencephaly is a severe malformation of the CNS, morphological characterization could improve the screening by US that is mandatory in the first trimester in order to plan the best, safe and early management.


Assuntos
Anencefalia/etiologia , Polimorfismo Genético/genética , Anencefalia/patologia , Feminino , Humanos , Masculino
4.
Epigenetics Chromatin ; 12(1): 76, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856916

RESUMO

BACKGROUND: Neural tube defects (NTDs) are severe, common birth defects that result from failure of normal neural tube closure during early embryogenesis. Accumulating strong evidence indicates that genetic factors contribute to NTDs etiology, among them, HOX genes play a key role in neural tube closure. Although abnormal HOX gene expression can lead to NTDs, the underlying pathological mechanisms have not fully been understood. METHOD: We detected that H3K27me3 and expression of the Hox genes in a retinoic acid (RA) induced mouse NTDs model on E8.5, E9.5 and E10.5 using RNA-sequencing and chromatin immunoprecipitation sequencing assays. Furthermore, we quantified 10 Hox genes using NanoString nCounter in brain tissue of fetuses with 39 NTDs patients including anencephaly, spina bifida, hydrocephaly and encephalocele. RESULTS: Here, our results showed differential expression in 26 genes with a > 20-fold change in the level of expression, including 10 upregulated Hox genes. RT-qPCR revealed that these 10 Hox genes were all upregulated in RA-induced mouse NTDs as well as RA-treated embryonic stem cells (ESCs). Using ChIP-seq assays, we demonstrate that a decrease in H3K27me3 level upregulates the expression of Hox cluster A-D in RA-induced mouse NTDs model on E10.5. Interestingly, RA treatment led to attenuation of H3K27me3 due to cooperate between UTX and Suz12, affecting Hox gene regulation. Further analysis, in human anencephaly cases, upregulation of 10 HOX genes was observed, along with aberrant levels of H3K27me3. Notably, HOXB4, HOXC4 and HOXD1 expression was negatively correlated with H3K27me3 levels. CONCLUSION: Our results indicate that abnormal HOX gene expression induced by aberrant H3K27me3 levels may be a risk factor for NTDs and highlight the need for further analysis of genome-wide epigenetic modification in NTDs.


Assuntos
Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Defeitos do Tubo Neural/patologia , Anencefalia/metabolismo , Anencefalia/patologia , Animais , Modelos Animais de Doenças , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Defeitos do Tubo Neural/induzido quimicamente , Complexo Repressor Polycomb 2/antagonistas & inibidores , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Tretinoína/toxicidade , Regulação para Cima/efeitos dos fármacos
5.
Cell Death Dis ; 10(10): 721, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558708

RESUMO

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.


Assuntos
Anencefalia/patologia , Apoptose , Encéfalo/patologia , Necrose/patologia , Defeitos do Tubo Neural/patologia , Medula Espinal/patologia , Líquido Amniótico/metabolismo , Anencefalia/induzido quimicamente , Anencefalia/embriologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/citologia , Encéfalo/embriologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Necrose/embriologia , Necrose/metabolismo , Neurônios/citologia , Neurônios/patologia , Proteína p130 Retinoblastoma-Like/genética , Proteína p130 Retinoblastoma-Like/metabolismo , Medula Espinal/citologia , Medula Espinal/embriologia , Medula Espinal/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Ácido Valproico
6.
Birth Defects Res ; 111(2): 41-52, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30537250

RESUMO

The aerodigestive and communicative behaviors of anencephalic and hydranencephalic patients are assessed from literature sources and are compared with documented neural structures present in the brainstem, subcortical, and cortical regions of the brain. Much of the data analyzed corroborate previous neurological studies, which focus on central pattern generators and development in model organisms. However, findings suggest that further research is necessary to determine which components of these systems support these behaviors. A low reporting rate of behavior in tandem with pathology is observed throughout the literature. More data pairing behavior and pathology is recommended, both in the interest of understanding the relationship between neural structures and functions, and to provide clinicians with more information about a patient's signs and symptoms. Potential clinical practices are recommended to increase documentation about patients within this population.


Assuntos
Anencefalia/patologia , Hidranencefalia/patologia , Encéfalo/patologia , Comunicação , Deglutição/fisiologia , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroimagem/métodos
7.
Congenit Anom (Kyoto) ; 57(5): 134-137, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28295633

RESUMO

Neural tube closure (NTC) is an embryonic process during formation of the mammalian central nervous system. Disruption of the dynamic, sequential events of NTC can cause neural tube defects (NTD) leading to spina bifida and anencephaly in the newborn. NTC is affected by inherent factors such as genetic mutation or if the mother is exposed to certain environmental factors such as intake of harmful chemicals, maternal infection, irradiation, malnutrition, and inadequate or excessive intake of specific nutrients. Although effects of these stress factors on NTC have been intensively studied, the metabolic state of a normally developing embryo remains unclear. State-of-the art mass spectrometry techniques have enabled detailed study of embryonic metabolite profiles and their distribution within tissues. This approach has demonstrated that glucose metabolism is altered during NTC stages involving chorioallantoic branching. An understanding of embryonic metabolic rewiring would help reveal the etiology of NTD caused by environmental factors.


Assuntos
Anencefalia/metabolismo , Metabolismo Energético/fisiologia , Glucose/metabolismo , Tubo Neural/metabolismo , Disrafismo Espinal/metabolismo , Anencefalia/etiologia , Anencefalia/patologia , Animais , Membrana Corioalantoide/metabolismo , Membrana Corioalantoide/patologia , Embrião de Mamíferos , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Troca Materno-Fetal/fisiologia , Metaboloma , Tubo Neural/anormalidades , Tubo Neural/embriologia , Gravidez , Disrafismo Espinal/etiologia , Disrafismo Espinal/patologia
8.
J Anat ; 230(6): 842-858, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28266009

RESUMO

Few descriptions of the musculoskeletal system of humans with anencephaly or spina bifida exist in the literature. Even less is published about individuals in which both phenomena occur together, i.e. about craniorachischisis. Here we provide a detailed report on the musculoskeletal structures of a fetus with craniorachischisis, as well as comparisons with the few descriptions for anencephaly and with musculoskeletal anomalies found in other congenital malformations. We focused in particular on the comparison with trisomies 13, 18, and 21 because neural tube defects have been associated with such chromosomal defects. Our results showed that many of the defects found in the fetus with craniorachischisis are similar not only to anomalies previously described in the available works on musculoskeletal phenotypes seen in fetuses with anencephaly and spina bifida, but also to a wide range of other different conditions/syndromes including trisomies 13, 18 and 21, and cyclopia. The fact that similar anomalies are seen commonly not only in a wide range of different syndromes, but also as variants of the normal human population and as the 'normal' phenotype of other animals, supports Pere Alberch's unfortunately named idea of a 'logic of monsters'. That is, it supports the idea that development is so constrained that both in 'normal' and abnormal development one sees certain outcomes being produced again and again because ontogenetic constraints only allow a few possible outcomes, thus also leading to cases where the anatomical defects of some organisms are similar to the 'normal' phenotype of other organisms. In fact, this applies not only to specific anomalies but also to general patterns, such as the fact that in pathological conditions affecting different regions of the body, one consistently sees more defects on the upper limbs than on the lower limbs. Such general patterns are, again, seen in the fetus examined for this study, which had 29 muscle anomalies on the right upper limb and 22 muscle anomalies on the left upper limb, vs. seven muscle anomalies on the right lower limb and two on the left lower limb. It is therefore hoped that this work, which is part of our effort to describe and compile information on human musculoskeletal defects found in a wide range of conditions, will contribute not only to a better understanding of craniorachischisis in particular and of human congenital malformations in general, but also to broader discussions on the fields of comparative anatomy, and developmental and evolutionary biology.


Assuntos
Anencefalia/patologia , Sistema Musculoesquelético/patologia , Disrafismo Espinal/patologia , Dissecação , Feto , Humanos , Masculino
9.
Birth Defects Res A Clin Mol Teratol ; 106(12): 993-1007, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27704687

RESUMO

BACKGROUND: Diprosopus is a subtype of symmetric conjoined twins with one head, facial duplication and a single trunk. Diprosopus is a very rare congenital anomaly. METHODS: This is a systematic review of published cases and the presentation of two new cases born in Argentina. We estimated the prevalence of conjoined twins and diprosopus using data from the National Network of Congenital Anomalies of Argentina (RENAC). RESULTS: The prevalence of conjoined twins in RENAC was 19 per 1,000,000 births (95% confidence interval, 12-29). Diprosopus prevalence was 2 per 1,000,000 births (95% confidence interval, 0.2-6.8). In the systematic review, we identified 31 diprosopus cases. The facial structures more frequently duplicated were nose and eyes. Most frequent associated anomalies were: anencephaly, duplication of cerebral hemispheres, craniorachischisis, oral clefts, spinal abnormalities, congenital heart defects, diaphragmatic hernia, thoracic and/or abdominal visceral laterality anomalies. One of the RENAC cases and three cases from the literature had another discordant nonmalformed twin. CONCLUSION: The conjoined twins prevalence was similar to other studies. The prevalence of diprosopus was higher. The etiology is still unknown. The presence of visceral laterality anomalies may indicate the link between diprosopus and the alteration or duplication of the primitive node in the perigastrulation period (12-15 days postfertilization). Pregnancies of more than two embryos may be a risk factor for diprosopus. Given the low prevalence of this defect, it would be useful to perform studies involving several surveillance systems and international consortiums. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:993-1007, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Anormalidades Múltiplas/epidemiologia , Cérebro/anormalidades , Face/anormalidades , Nariz/anormalidades , Gêmeos Unidos/patologia , Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/fisiopatologia , Anencefalia/epidemiologia , Anencefalia/patologia , Anencefalia/fisiopatologia , Argentina/epidemiologia , Fissura Palatina/epidemiologia , Fissura Palatina/patologia , Fissura Palatina/fisiopatologia , Feminino , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Hérnia Diafragmática/epidemiologia , Hérnia Diafragmática/patologia , Hérnia Diafragmática/fisiopatologia , Humanos , Masculino , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/patologia , Defeitos do Tubo Neural/fisiopatologia , Prevalência , Fatores de Risco , Gêmeos Unidos/fisiopatologia
10.
Birth Defects Res A Clin Mol Teratol ; 106(8): 685-95, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27166990

RESUMO

BACKGROUND: After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. METHODS: From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. CONCLUSION: Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Anencefalia/imunologia , Autoanticorpos/sangue , Autoimunidade/efeitos dos fármacos , Receptor 1 de Folato/antagonistas & inibidores , Ácido Fólico/imunologia , Imunoglobulina G/sangue , Adulto , Anencefalia/diagnóstico , Anencefalia/genética , Anencefalia/patologia , Estudos de Casos e Controles , China , Relação Dose-Resposta Imunológica , Tolerância a Medicamentos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/imunologia , Ácido Fólico/administração & dosagem , Expressão Gênica , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Risco
11.
Indian J Pathol Microbiol ; 58(3): 285-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26275247

RESUMO

INTRODUCTION: Neural tube defects (NTD) are a group of serious birth defects occurring due to defective closure of neural tube during embryonic development. It comprises of anencephaly, encephalocele and spina bifida. We conducted this prospective fetal autopsy series to study the rate and distribution of NTD, analyze the reproductive factors and risk factors, note any associated anomalies and evaluate the organ weights and their deviation from normal. MATERIALS AND METHODS: This was a prospective study done over a period of 6 years from August, 2007 to July, 2013. All cases of NTDs delivered as abortion, still born and live born were included. The reproductive and risk factors like age, parity, multiple births, previous miscarriage, obesity, diabetes mellitus, socioeconomic status and use of folic acid during pregnancy were collected.Autopsy was performed according to Virchow's technique. Detail external and internal examination were carried out to detect any associated anomalies. Gross and microscopic examination of organs were done. RESULTS: Out of 210 cases of fetal and perinatal autopsy done, 72 (34.28%) had NTD constituting 49 cases of anencephaly, 16 spina bifida and 7 cases of encephalocele. The mothers in these cases predominantly were within 25-29 years (P = 0.02) and primy (P = 0.01). Female sex was more commonly affected than males (M:F = 25:47, P = 0.0005) There was no history of folate use in majority of cases. Organ weight deviations were >2 standard deviation low in most of the cases. Most common associated anomalies were adrenal hypoplasia and thymic hyperplasia. CONCLUSION: The authors have made an attempt to study NTD cases in respect to maternal reproductive and risk factors and their association with NTD along with the organ weight deviation and associated anomalies. This so far in our knowledge is an innovative study which was not found in literature even after extensive search.


Assuntos
Anencefalia/epidemiologia , Anencefalia/patologia , Autopsia , Encefalocele/epidemiologia , Encefalocele/patologia , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/patologia , Adulto , Feminino , Humanos , Masculino , Tamanho do Órgão , Gravidez , Estudos Prospectivos , Fatores de Risco
12.
Int J Legal Med ; 129(4): 903-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25416960

RESUMO

One of the most common conditions during fetal development is anencephaly, which often involves many identification difficulties in the context of physical anthropology, as it causes severe skull challenges. In this paper, we describe the alterations found in the skulls of two perinatal individuals with anencephaly from the osteological collection of identified infants in the Anthropology Laboratory of the University of Granada, Spain. Both subjects of study are in perfect state of preservation. Despite the severe malformations, all skull bones have been targeted and identified, as the possibility of studying a subject with a complete, articulated, and partially mummified skull; the other was disjointed and well preserved. The skull bones of these two individuals affected with anencephaly have been described in detail, allowing this pathological condition to be identified in skeletonized individuals in archaeological or forensic contexts, in cases where these bones did not have anatomical connection or when these were taphonomically altered.


Assuntos
Anencefalia/patologia , Crânio/anormalidades , Crânio/patologia , Feminino , Feto , Patologia Legal , Humanos , Recém-Nascido
13.
Birth Defects Res A Clin Mol Teratol ; 103(6): 554-66, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25360518

RESUMO

BACKGROUND: Oropharyngeal teratoma may occur by itself or together with other craniofacial malformations, most commonly cleft palate. Oropharyngeal teratoma may be also seen in association with frontonasal dysplasia and/or various degrees of craniofacial duplication. The nosology of these sporadic disorders is poorly defined. CASE AND REVIEW: We report on a 22-week fetus with a protruding nasopharyngeal teratoma, partial oral duplication, anencephaly, multiple costo-vertebral segmentation defects, and cervical diplomyelia. A review of the literature identified 48 patients published from 1931 to 2013 with co-existing clefting and duplication anomalies of the cephalic pole. Thoracic and abdominal midline anomalies were reported 13 times. CONCLUSION: The term "craniofacial teratoma syndrome" is introduced to define this phenotype as a recognizable developmental field defect of the cephalic pole. Developmental pathogenesis is discussed with a focus on pleiotropy and stereotaxis. The observation of midline findings suggestive of holoprosencephaly in a few previously reported cases suggests a role for the sonic hedgehog signaling pathway in this malformation pattern.


Assuntos
Anormalidades Múltiplas/patologia , Anencefalia/patologia , Vértebras Cervicais/anormalidades , Feto/patologia , Anormalidades da Boca/patologia , Neoplasias Orofaríngeas/patologia , Teratoma/patologia , Humanos , Síndrome , Terminologia como Assunto
14.
Neonatal Netw ; 33(6): 315-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25391590

RESUMO

Traditional organ transplant options for newborns have been rare. There continues to be an increasing need for organs for transplant and a limited number of available organs, especially for small children. Liver cell transplantation is a promising alternative to orthotopic liver transplantation to treat liver-based inborn errors of metabolism.1 The procedure is minimally invasive and can be performed repeatedly. The safety of the procedure has been well established, and the clinical results are encouraging.1 The liver cell donation process is an option for families who experience the loss of a newborn and offers them a legacy for their child by providing life for others. The purpose of this article is to discuss the neonatal liver cell donation process and present a case report of an anencephalic infant whose parents chose to participate in this unique program.


Assuntos
Anencefalia/enfermagem , Anencefalia/patologia , Terapia Baseada em Transplante de Células e Tecidos/enfermagem , Hepatócitos/transplante , Transplante de Fígado/enfermagem , Obtenção de Tecidos e Órgãos , Adulto , Anencefalia/diagnóstico por imagem , Comportamento Cooperativo , Feminino , Humanos , Recém-Nascido , Comunicação Interdisciplinar , Gravidez , Ordens quanto à Conduta (Ética Médica) , Ultrassonografia Pré-Natal/enfermagem
15.
Artigo em Inglês | MEDLINE | ID: mdl-24902834

RESUMO

The neural tube (NT), the embryonic precursor of the vertebrate brain and spinal cord, is generated by a complex and highly dynamic morphological process. In mammals, the initially flat neural plate bends and lifts bilaterally to generate the neural folds followed by fusion of the folds at the midline during the process of neural tube closure (NTC). Failures in any step of this process can lead to neural tube defects (NTDs), a common class of birth defects that occur in approximately 1 in 1000 live births. These severe birth abnormalities include spina bifida, a failure of closure at the spinal level; craniorachischisis, a failure of NTC along the entire body axis; and exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly. The mouse embryo presents excellent opportunities to explore the genetic basis of NTC in mammals; however, its in utero development has also presented great challenges in generating a deeper understanding of how gene function regulates the cell and tissue behaviors that drive this highly dynamic process. Recent technological advances are now allowing researchers to address these questions through visualization of NTC dynamics in the mouse embryo in real time, thus offering new insights into the morphogenesis of mammalian NTC.


Assuntos
Morfogênese , Crista Neural/crescimento & desenvolvimento , Placa Neural/crescimento & desenvolvimento , Tubo Neural/crescimento & desenvolvimento , Anencefalia/genética , Anencefalia/patologia , Animais , Camundongos , Placa Neural/patologia , Tubo Neural/patologia , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Disrafismo Espinal/genética , Disrafismo Espinal/patologia
16.
Genet Mol Res ; 13(1): 1015-29, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24634123

RESUMO

Anencephaly is one of the most serious forms of neural tube defects (NTDs), a group of congenital central nervous system (CNS) malformations. MicroRNAs (miRNAs) are involved in diverse biological processes via the post-transcriptional regulation of target mRNAs. Although miRNAs play important roles in the development of mammalian CNS, their function in human NTDs remains unknown. Using a miRNA microarray, we identified a unique expression profile in fetal anencephalic brain tissues, characterized by 70 upregulated miRNAs (ratio ≥ 2) and 7 downregulated miRNAs (ratio ≤ 0.5) compared with healthy human samples. Ten miRNAs with altered expression were selected from the microarray findings for validation with real-time quantitative reverse transcription-polymerase chain reaction. We found that in anencephalic tissues, miR-22, miR-23a, miR-34a, miR-103, miR-125a, miR-132, miR-134, miR-138, and miR-185 were significantly upregulated, while miR-149 was significantly downregulated. Furthermore, 459 potential target genes within the validated miRNAs were revealed using combined four target prediction algorithms in the human genome, and subsequently analyzed with the Molecule Annotation System 3.0. A total of 119 target genes were ultimately identified, including those involved in 22 singular annotations (i.e., transcription, signal transduction, and cell cycle) and 55 functional pathways [i.e., mitogen-activated protein kinase (MAPK) signaling pathway, and actin cytoskeleton regulation]. Six target genes (HNRPU, JAG1, FMR1, EGR3, RUNX1T1, and NDEL1) were chosen as candidate genes and associated with congenital birth abnormalities of the brain structure. Our results, therefore, suggest that miRNA maladjustment mainly contributes to the etiopathogenesis of anencephaly via the MAPK signaling pathway.


Assuntos
Anencefalia/patologia , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Feto Abortado/citologia , Anencefalia/genética , Feminino , Regulação da Expressão Gênica , Genômica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real
17.
Birth Defects Res A Clin Mol Teratol ; 100(2): 100-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24535840

RESUMO

BACKGROUND: Folic acid supplements can protect against neural tube defects (NTDs). Low folate and low vitamin B12 status may be maternal risk factors for having an NTD affected pregnancy. However, not all NTDs are preventable by having an adequate folate/ B12 status and other potentially modifiable factors may be involved. Folate and vitamin B12 status have important links to iron metabolism. Animal studies support an association between poor iron status and NTDs, but human data are scarce. We examined the relevance of low iron status in a nested NTD case-control study of women within a pregnant population-based cohort. METHODS: Pregnant women were recruited between 1986 and 1990, when vitamin or iron supplementation in early pregnancy was rare. Blood samples, taken at an average of 14 weeks gestation, were used to measure ferritin and hemoglobin in 64 women during an NTD affected pregnancy and 207 women with unaffected pregnancies. RESULTS: No significant differences in maternal ferritin or hemoglobin concentrations were observed between NTD affected and nonaffected pregnancies (case median ferritin 16.9 µg/L and hemoglobin 12.4 g/dl versus 15.4 µg/L and 12.3g/dl in controls). As reported previously, red cell folate and vitamin B12 concentrations were significantly lower in cases. Furthermore, there was no significant association of iron status with type of NTD lesion (anencephaly or spina bifida). CONCLUSION: We conclude that low maternal iron status during early pregnancy is not an independent risk factor for NTDs. Adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent NTDs.


Assuntos
Anencefalia/sangue , Ferritinas/sangue , Hemoglobinas/metabolismo , Ferro/sangue , Disrafismo Espinal/sangue , Adulto , Anencefalia/diagnóstico , Anencefalia/patologia , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Ferro/metabolismo , Fatores de Risco , Disrafismo Espinal/diagnóstico , Disrafismo Espinal/patologia
18.
Med Secoli ; 26(1): 23-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25702380

RESUMO

Anencephaly is of special interest for the historical study of human behaviour after the birth of a monstrous child. Examples of anencephalic human births from Egyptian Antiquity to the present time allow us to create a history of teratology, revealing hiatuses in the medical and scientific interpretation of monstrosity that contrast to a relative continuity in the imaginary processes that accompany the birth of a monstrous child.


Assuntos
Anormalidades Teratoides Graves/história , Anencefalia/história , Anormalidades Teratoides Graves/patologia , Anencefalia/patologia , Egito , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Recém-Nascido
19.
Int. braz. j. urol ; 39(6): 853-860, Nov-Dec/2013. tab, graf
Artigo em Inglês | LILACS | ID: lil-699126

RESUMO

Purpose The objective of this paper is to analyze the structure of the ureter in normal and anencephalic human fetuses. Materials and Methods We studied 16 ureters from 8 human fetuses without congenital anomalies aged 16 to 27 weeks post-conception (WPC) and 14 ureters from 7 anencephalic fetuses aged 19 to 33 WPC. The ureters were dissected and embedded in paraffin, from which 5 µm thick sections were obtained and stained with Masson trichrome, to quantify smooth muscle cells (SMC) and to determine the ureteral lumen area, thickness and ureteral diameter. The samples were also stained with Weigert Resorcin Fucsin (to study elastic fibers) and Picro-Sirius Red with polarization and immunohistochemistry analysis of the collagen type III fibers to study collagen. Stereological analysis of collagen, elastic system fibers and SMC were performed on the sections. Data were expressed as volumetric density (Vv-%). The images were captured with an Olympus BX51 microscope and Olympus DP70 camera. The stereological analysis was done using the Image Pro and Image J programs. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p < 0.05). Results The ureteral epithelium was well preserved in the anencephalic and control groups. We did not observe differences in the transitional epithelium in the anencephalic and control groups. There was no difference in elastic fibers and total collagen distribution in normal and anencephalic fetuses. SMC concentration did not differ significantly (p = 0.1215) in the anencephalic and control group. The ureteral lumen area (p = 0.0047), diameter (p = 0.0024) and thickness (p = 0.0144) were significantly smaller in anencephalic fetuses. Conclusions Fetuses with anencephaly showed smaller diameter, area and thickness. These differences could indicate ...


Assuntos
Feminino , Humanos , Lactente , Masculino , Anencefalia/patologia , Feto/ultraestrutura , Ureter/anormalidades , Estudos de Casos e Controles , Colágeno/análise , Tecido Elástico/embriologia , Imuno-Histoquímica , Miócitos de Músculo Liso , Estatísticas não Paramétricas , Ureter/embriologia , Ureter/ultraestrutura
20.
Wiley Interdiscip Rev Dev Biol ; 2(2): 213-27, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24009034

RESUMO

Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. 'Open' NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida), and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. 'Closed' NTDs are skin-covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. 'Herniation' NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorized through a pathological opening in the skull or vertebral column (e.g., encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signaling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the bone morphogenetic protein and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid (FA), when taken as a periconceptional supplement, can prevent many cases. Not all NTDs respond to FA, however, and adjunct therapies are required for prevention of this FA-resistant category.


Assuntos
Anencefalia/patologia , Meningomielocele/patologia , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Neurulação/genética , Anencefalia/genética , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Desenvolvimento Embrionário , Ácido Fólico/administração & dosagem , Ácido Fólico/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Meningomielocele/genética , Camundongos
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