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Revista Medica Del Instituto Mexicano... 2018In this paper the relationship between the incidence of microcephaly and various arboviruses in current boom is exposed. It stands out that in the infection by the...
In this paper the relationship between the incidence of microcephaly and various arboviruses in current boom is exposed. It stands out that in the infection by the dengue virus, there have been no cases of microcephaly, however in the case series of chikungunya infection, incidence of cases with this affectation was reported, highlighting a cohort called CHIMERE; also the highest incidence of microcephaly associated with the mentioned Zika virus, which has been widely studied. All this, due to the neurotropism of these arboviruses.
Topics: Americas; Arbovirus Infections; Humans; Microcephaly
PubMed: 29906032
DOI: No ID Found -
Cells Jul 2022How the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man's place in the animal kingdom.... (Review)
Review
How the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man's place in the animal kingdom. Although animal models have so far been highly valuable in understanding the key steps of cortical development, many human specificities call for appropriate models. In particular, microcephaly, a neurodevelopmental disorder that is characterized by a smaller head circumference has been challenging to model in mice, which often do not fully recapitulate the human phenotype. The relatively recent development of brain organoid technology from induced pluripotent stem cells (iPSCs) now makes it possible to model human microcephaly, both due to genetic and environmental origins, and to generate developing cortical tissue from the patients themselves. These 3D tissues rely on iPSCs differentiation into cortical progenitors that self-organize into neuroepithelial rosettes mimicking the earliest stages of human neurogenesis in vitro. Over the last ten years, numerous protocols have been developed to control the identity of the induced brain areas, the reproducibility of the experiments and the longevity of the cultures, allowing analysis of the later stages. In this review, we describe the different approaches that instruct human iPSCs to form cortical organoids, summarize the different microcephalic conditions that have so far been modeled by organoids, and discuss the relevance of this model to decipher the cellular and molecular mechanisms of primary and secondary microcephalies.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Mice; Microcephaly; Neurogenesis; Organoids; Reproducibility of Results
PubMed: 35883578
DOI: 10.3390/cells11142135 -
Arquivos de Neuro-psiquiatria Jan 2015
Topics: Facies; Hirschsprung Disease; Humans; Intellectual Disability; Microcephaly
PubMed: 25608118
DOI: 10.1590/0004-282X20140224 -
Microbes and Infection Dec 2018Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other... (Review)
Review
Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other neonatal alterations. This review will discuss lessons learned from viral pathogenesis, epidemiology and clinical findings observed during the ZIKV outbreak occurred between 2014 and 2016 in Brazil.
Topics: Brazil; Disease Outbreaks; Female; Humans; Microcephaly; Placenta; Pregnancy; Viral Tropism; Zika Virus; Zika Virus Infection
PubMed: 29501560
DOI: 10.1016/j.micinf.2018.02.008 -
Seminars in Cell & Developmental Biology Apr 2018Primary microcephaly (PM) refers to a congenitally small brain, resulting from insufficient prenatal production of neurons, and serves as a model disease for brain... (Review)
Review
Primary microcephaly (PM) refers to a congenitally small brain, resulting from insufficient prenatal production of neurons, and serves as a model disease for brain volumic development. Known PM genes delineate several cellular pathways, among which the centriole duplication pathway, which provide interesting clues about the cellular mechanisms involved. The general interest of the genetic dissection of PM is illustrated by the convergence of Zika virus infection and PM gene mutations on congenital microcephaly, with CENPJ/CPAP emerging as a key target. Physical (protein-protein) and genetic (digenic inheritance) interactions of Wdr62 and Aspm have been demonstrated in mice, and should now be sought in humans using high throughput parallel sequencing of multiple PM genes in PM patients and control subjects, in order to categorize mutually interacting genes, hence delineating functional pathways in vivo in humans.
Topics: Brain; Humans; Microcephaly; Mutation; Nervous System Malformations
PubMed: 28912110
DOI: 10.1016/j.semcdb.2017.09.015 -
Current Opinion in Pediatrics Feb 2017Zika virus (ZIKV) is the latest 'emerging virus' that has affected the Americas. First identified in the mid-20th century in Uganda, it was described as a vector... (Review)
Review
PURPOSE OF REVIEW
Zika virus (ZIKV) is the latest 'emerging virus' that has affected the Americas. First identified in the mid-20th century in Uganda, it was described as a vector arthropod-borne virus (arbovirus) and subsequently found capable of producing illness in humans. The illness was not different from other flavivirus infections and caused a relatively mild disease characterized by low-grade fever, nonspecific exanthem, nonpurulent conjunctivitis, and mild to moderate arthralgia. It was capable of producing infections described as sporadic isolated cases; in 2007, it was confirmed as the pathogen causing the first known ZIKV epidemic subsequently associated with congenital neonatal microcephaly in many countries in the Americas.
RECENT FINDINGS
It rapidly spread to other countries in the Americas and, as of September 2016, it has been detected in 46 countries and territories. Different from other flavivirus infections, ZIKV has proven to be related to more serious complications. These include Guillain-Barré syndrome and neonatal congenital malformations, which includes microcephaly and neurologic damage to the developing fetus, particularly if the maternal infection occurs early in pregnancy. These two complications are a cause of great concern.
SUMMARY
It is pivotal to conduct epidemiological laboratory-based surveillance and studies on the virus' inherent characteristics to understand the pathophysiology of this infection and develop adequate strategies to mitigate this new threat.
Topics: Americas; Guillain-Barre Syndrome; Humans; Microcephaly; Zika Virus Infection
PubMed: 27845968
DOI: 10.1097/MOP.0000000000000442 -
NeoReviews Apr 2022
Topics: Female; Humans; Infant, Newborn; Microcephaly; Pregnancy; Pregnancy Complications, Infectious
PubMed: 35362040
DOI: 10.1542/neo.23-4-e279 -
Trends in Molecular Medicine Sep 2017The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon... (Review)
Review
The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon fetal exposure. Significant progress has been made in our understanding of the interactions between ZIKV and the pregnant host, but there is still a critical need to understand how ZIKV and other neurotropic viruses affect fetal neurodevelopment. Diaphanous-related formins (Diaphs) have recently been identified as microcephaly-associated proteins in humans and mice. Mutations in Diaphs affect the function of neural progenitor cells, much like prenatal viral infection. We present a novel hypothesis that viruses 'hijack' Diaphs in neural progenitor cells, causing autonomous differentiation and apoptosis of neural progenitor cells, which could potentially contribute to virus-associated neurological pathologies.
Topics: Adaptor Proteins, Signal Transducing; Animals; Disease Outbreaks; Formins; Humans; Microcephaly; Neural Stem Cells; Zika Virus; Zika Virus Infection
PubMed: 28803703
DOI: 10.1016/j.molmed.2017.07.004 -
Dialogues in Clinical Neuroscience Dec 2018Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social... (Review)
Review
Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social abilities. Cortical expansion is determined through a tightly orchestrated process of neural stem cell proliferation, migration, and ongoing organization, synaptogenesis, and apoptosis. Perturbations of each of these intricate steps can lead to abnormalities of brain size in humans, whether small (microcephaly) or large (megalencephaly). Abnormalities of brain growth can be clinically isolated or occur as part of complex syndromes associated with other neurodevelopmental problems (eg, epilepsy, autism, intellectual disability), brain malformations, and body growth abnormalities. Thorough review of the genetic literature reveals that human microcephaly and megalencephaly are caused by mutations of a rapidly growing number of genes linked within critical cellular pathways that impact early brain development, with important pathomechanistic links to cancer, body growth, and epilepsy. Given the rapid rate of causal gene identification for microcephaly and megalencephaly understanding the roles and interplay of these important signaling pathways is crucial to further unravel the mechanisms underlying brain growth disorders and, more fundamentally, normal brain growth and development in humans. In this review, we will (a) overview the definitions of microcephaly and megalencephaly, highlighting their classifications in clinical practice; (b) overview the most common genes and pathways underlying microcephaly and megalencephaly based on the fundamental cellular processes that are perturbed during cortical development; and (c) outline general clinical molecular diagnostic workflows for children and adults presenting with microcephaly and megalencephaly.
Topics: Autistic Disorder; Brain; Humans; Megalencephaly; Microcephaly; Mutation; Organ Size
PubMed: 30936767
DOI: 10.31887/DCNS.2018.20.4/gmirzaa -
Journal of Paediatrics and Child Health Mar 2022To describe clinical characteristics, outcomes and causes of microcephaly in children whose condition was identified within the first year of life.
AIM
To describe clinical characteristics, outcomes and causes of microcephaly in children whose condition was identified within the first year of life.
METHODS
Retrospective review of medical records of microcephalic children born between 2008 and 2018 and admitted for any reason during the same period to a tertiary paediatric hospital. Microcephaly was defined as occipitofrontal circumference (OFC) more than two standard deviations below the mean (>-2 SD).
RESULTS
Between January 2008 and September 2018, 1083 medical records were retrieved. Of the children, 886 were ineligible and 197 were confirmed cases of microcephaly. Of cases, 73 (37%) had primary microcephaly (at birth) and 72 (37%) had severe microcephaly (OFC > -3 SD). Of microcephalic children, 192 (98%) had congenital anomalies, of whom 93% had major anomalies, mostly cardiovascular or musculoskeletal. Neurological signs or symptoms were reported in 148 (75%), seizures being the most common. Of the 139 children with abnormal central nervous system (CNS) imaging, one or more structural brain abnormalities were identified in 124 (89%). Failure to reach developmental milestones was observed in 69%, visual impairment in 41% and cerebral palsy in 13%. Microcephaly was idiopathic in 51% and 24% had diagnosed genetic disorders. There was no association between developmental outcomes or structural brain anomalies and severity of microcephaly or timing of diagnosis.
CONCLUSION
Our results suggest the need for a systematic investigative approach to diagnosis, including a careful history, examination, genetic testing and neuroimaging, to determine the underlying cause of microcephaly, identify co-morbidities, predict prognosis and guide genetic counselling and therapy.
Topics: Australia; Child; Humans; Infant; Infant, Newborn; Microcephaly; Nervous System Malformations; Neuroimaging; Retrospective Studies
PubMed: 34553803
DOI: 10.1111/jpc.15739