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Chinese Medical Journal Oct 2016To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation... (Review)
Review
OBJECTIVE
To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly.
DATA SOURCES
We did a comprehensive literature review with the keywords "zika" and/or "microcephaly" from inception to May 27, 2016, with PubMed.
STUDY SELECTION
Studies were included and analyzed if they met all of the following criteria: "probable or confirmed infant microcephaly" and "probable or confirmed ZIKV infection among mothers or infants".
RESULTS
We emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious "diagnosed" microcephaly.
CONCLUSIONS
There are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions.
Topics: Animals; Female; Humans; Microcephaly; Mutation; Pregnancy; Zika Virus; Zika Virus Infection
PubMed: 27647195
DOI: 10.4103/0366-6999.190672 -
Cell Cycle (Georgetown, Tex.) Feb 2017
Topics: Animals; Biological Evolution; Humans; Intracellular Signaling Peptides and Proteins; Microcephaly; Microtubules; Models, Biological; Protein Serine-Threonine Kinases; Spindle Apparatus
PubMed: 27830983
DOI: 10.1080/15384101.2016.1252584 -
Genes & Development May 2017The re-emergence of Zika virus (ZIKV), a mosquito-borne and sexually transmitted flavivirus circulating in >70 countries and territories, poses a significant global... (Review)
Review
The re-emergence of Zika virus (ZIKV), a mosquito-borne and sexually transmitted flavivirus circulating in >70 countries and territories, poses a significant global threat to public health due to its ability to cause severe developmental defects in the human brain, such as microcephaly. Since the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern, remarkable progress has been made to gain insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection. Here we review the current knowledge and progress in understanding the impact of ZIKV exposure on the mammalian brain development and discuss potential underlying mechanisms.
Topics: Animals; Disease Outbreaks; Humans; Microcephaly; Zika Virus; Zika Virus Infection
PubMed: 28566536
DOI: 10.1101/gad.298216.117 -
American Journal of Medical Genetics.... Oct 2022Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X-linked syndrome presenting with intellectual disability (ID), autism...
Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X-linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10-related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10, inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt-bridge between Arg32 and Asp28. In addition to features consistent with RPL10-related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10-related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.
Topics: Autism Spectrum Disorder; Humans; Intellectual Disability; Male; Microcephaly; Nervous System Malformations; Phenotype
PubMed: 35876338
DOI: 10.1002/ajmg.a.62911 -
Viruses May 2018The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal... (Review)
Review
The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain⁻Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV⁻host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV⁻host Interactions.
Topics: Animals; Host-Pathogen Interactions; Humans; Immunity, Innate; Mice; Microcephaly; Nervous System Diseases; Virus Internalization; Zika Virus; Zika Virus Infection
PubMed: 29724036
DOI: 10.3390/v10050233 -
Archives of Pathology & Laboratory... Jan 2017-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. (Review)
Review
CONTEXT
-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants.
OBJECTIVES
-To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions.
DATA SOURCES
-Comprehensive review of published scientific literature.
CONCLUSIONS
-Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.
Topics: Animals; Female; Fetal Diseases; Humans; Infectious Disease Transmission, Vertical; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 27636525
DOI: 10.5858/arpa.2016-0382-RA -
Developmental Medicine and Child... Aug 2014The aim of this study was to assess the diagnostic approach to microcephaly in childhood and to identify the prevalence of the various underlying causes/disease entities. (Review)
Review
AIM
The aim of this study was to assess the diagnostic approach to microcephaly in childhood and to identify the prevalence of the various underlying causes/disease entities.
METHOD
We conducted a retrospective study on a cohort of 680 children with microcephaly (399 males, 281 females; mean age at presentation 7-8mo, range 1mo-5y) from patients presenting to Charité - University Medicine Berlin (n=474) and University Hospital Dresden (n=206). Patient discharge letters were searched electronically to identify cases of microcephaly, and then the medical records of these patients were used to analyze parameters for distribution.
RESULTS
The putative aetiology for microcephaly was ascertained in 59% of all patients, leaving 41% without a definite diagnosis. In the cohort of pathogenetically defined microcephaly, genetic causes were identified in about half of the patients, perinatal brain damage accounted for 45%, and postnatal brain damage for 3% of the cases. Microcephaly was associated with intellectual impairment in 65% of participants, epilepsy was diagnosed in 43%, and ophthalmological disorders were found in 30%. Brain magnetic resonance imaging revealed abnormalities in 76% of participants.
INTERPRETATION
Microcephaly remains a poorly defined condition, and a uniform diagnostic approach is urgently needed. A definite aetiological diagnosis is important in order to predict the prognosis and offer genetic counselling. Identifying gene mutations as causes of microcephaly increases our knowledge of brain development and the clinical spectrum of microcephaly. We therefore propose a standardized initial diagnostic approach to microcephaly.
Topics: Child, Preschool; Comorbidity; Epilepsy; Eye Diseases; Female; Germany; Humans; Infant; Intellectual Disability; Male; Microcephaly; Practice Guidelines as Topic; Retrospective Studies
PubMed: 24617602
DOI: 10.1111/dmcn.12425 -
Genes Aug 2023-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including... (Review)
Review
-related disorders are a form of rare X-linked neurological diseases and most of the patients are females. They are characterized by several symptoms, including microcephaly with pontine and cerebellar hypoplasia (MICPCH), epilepsy, congenital nystagmus, and neurodevelopmental disorders. Whole-genome sequencing has identified various mutations, including nonsense and missense mutations, from patients with -related disorders, revealing correlations between specific mutations and clinical phenotypes. Notably, missense mutations associated with epilepsy and intellectual disability were found throughout the whole region of the CASK protein, while missense mutations related to microcephaly and MICPCH were restricted in certain domains. To investigate the pathophysiology of -related disorders, research groups have employed diverse methods, including the generation of knockout mice and the supplementation of CASK to rescue the phenotypes. These approaches have yielded valuable insights into the identification of functional domains of the CASK protein associated with a specific phenotype. Additionally, recent advancements in the AI-based prediction of protein structure, such as AlphaFold2, and the application of genome-editing techniques to generate mutant mice carrying missense mutations from patients with -related disorders, allow us to understand the pathophysiology of -related disorders in more depth and to develop novel therapeutic methods for the fundamental treatment of -related disorders.
Topics: Female; Animals; Mice; Male; Microcephaly; Mutation; Mice, Knockout; Phenotype; Rare Diseases
PubMed: 37628707
DOI: 10.3390/genes14081656 -
Canadian Family Physician Medecin de... Aug 2015To provide an evidence-based update emphasizing the importance of measuring head circumference (HC) in infants, with a focus on microcephaly. (Review)
Review
OBJECTIVE
To provide an evidence-based update emphasizing the importance of measuring head circumference (HC) in infants, with a focus on microcephaly.
QUALITY OF EVIDENCE
PubMed and EMBASE (OvidSP) were searched. Search terms used were head circumference and infants and measurement; microcephaly and infants and measurement; idiopathic microcephaly and infants; and congenital microcephaly and infants. Most of the references for this review were published in 2000 or later. Most evidence is level II.
MAIN MESSAGE
Serial measurement of HC should be incorporated into routine well-child care. Measure the distance around the back of the child's head with a nonelastic tape measure held above the eyebrows and ears, and plot the measurement on an age- and sex-appropriate growth chart. Microcephaly is HC more than 2 SD below the mean. The most common disability associated with microcephaly is intellectual delay; other common concomitant conditions include epilepsy, cerebral palsy, language delay, strabismus, ophthalmologic disorders, and cardiac, renal, urinary tract, and skeletal anomalies. An interdisciplinary approach to microcephaly is warranted. Although there are no specific interventions to enhance brain growth, dietary or surgical interventions might be helpful in some cases. Infants with microcephaly who show developmental delays might benefit from early intervention programs or developmental physical and occupational therapy.
CONCLUSION
Early identification of HC concerns by family physicians can be a critical first step in identifying disorders such as microcephaly, leading to referral to pediatric specialists and, as needed, provision of family-centred early intervention services.
Topics: Cephalometry; Child Development; Developmental Disabilities; Evidence-Based Medicine; Growth Charts; Humans; Infant; Microcephaly; Physical Examination
PubMed: 26505062
DOI: No ID Found -
Molecular Biology Reports Apr 2020Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born... (Review)
Review
Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.
Topics: Brain; Brazil; Disease Outbreaks; Female; Humans; Infant; Microcephaly; Pregnancy; Public Health; Zika Virus; Zika Virus Infection
PubMed: 32128708
DOI: 10.1007/s11033-020-05349-y