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Ophthalmology. Retina Sep 2022
Topics: Humans; Kinesins; Microcephaly; Mutation; Retina
PubMed: 36084995
DOI: 10.1016/j.oret.2022.06.002 -
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 -
Congenital Anomalies Jan 2021We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the...
We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not-Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not-Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of NDTs and MIC are significantly higher than in not-Polissia. In Polissia, the prevalence rates of NDTs and MIC are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re-ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate, and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken.
Topics: Blood Cell Count; Cesium Radioisotopes; Chernobyl Nuclear Accident; Congenital Abnormalities; Female; Geography, Medical; Humans; Microcephaly; Neural Tube Defects; Pregnancy; Prevalence; Public Health Surveillance; Ukraine
PubMed: 33405251
DOI: 10.1111/cga.12388 -
BMC Medical Genomics 2015Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental... (Review)
Review
Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder.
Topics: Animals; Humans; Microcephaly; Mutation; Saudi Arabia
PubMed: 25951892
DOI: 10.1186/1755-8794-8-S1-S4 -
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 -
Journal of Infection and Public Health Jan 2020Zika virus (ZIKV), a mosquito transmitted virus in the family Flaviviridae, genus Flavivirus, recently emerged to cause infections in more than 70 countries and... (Review)
Review
Zika virus (ZIKV), a mosquito transmitted virus in the family Flaviviridae, genus Flavivirus, recently emerged to cause infections in more than 70 countries and territories around the world. While human infection is normally asymptomatic, it can also result in a mild febrile disease similar to dengue fever. However, when a pregnant woman is infected, ZIKV can cause fetal abnormalities including microcephaly. Evidence has suggested that ZIKV has circulated in Southeast Asia for more than a decade and yet cases of ZIKV associated microcephaly remain sparsely documented. This review seeks to collate the information currently existing on ZIKV associated microcephaly in Southeast Asia, and assess the potential future risk posed by this virus.
Topics: Asia, Southeastern; Disease Outbreaks; Female; Global Health; Humans; Infectious Disease Transmission, Vertical; Microcephaly; Pregnancy; Pregnant Women; Zika Virus; Zika Virus Infection
PubMed: 31669035
DOI: 10.1016/j.jiph.2019.09.012 -
Developmental Medicine and Child... Apr 2022To characterize the cortical structure, developmental, and cognitive profiles of patients with WD repeat domain 62 (WDR62)-related primary microcephaly. (Observational Study)
Observational Study
AIM
To characterize the cortical structure, developmental, and cognitive profiles of patients with WD repeat domain 62 (WDR62)-related primary microcephaly.
METHOD
In this observational study, we describe the developmental, neurological, cognitive, and brain imaging characteristics of 17 patients (six males, 11 females; mean age 12y 3mo standard deviation [SD] 5y 8mo, range 5y-24y 6mo) and identify 14 new variants of WDR62. We similarly analyse the phenotypes and genotypes of the 59 previously reported families.
RESULTS
Brain malformations, including pachygyria, neuronal heterotopia, schizencephaly, and microlissencephaly, were present in 11 out of 15 patients. The mean full-scale IQ of the 11 assessed patients was 51.8 (standard deviation [SD] 12.6, range 40-70). Intellectual disability was severe in four patients, moderate in four, and mild in three. Scores on the Vineland Adaptive Behavior Scales obtained from 10 patients were low for communication and motor skills (mean 38.29, SD 7.74, and 37.71, SD 5.74 respectively). The socialization score was higher (mean 47.14, SD 12.39). We found a significant difference between scores for communication and daily living skills (mean 54.43, SD 11.6; p=0.001, one-way analysis of variance). One patient displayed progressive ataxia.
INTERPRETATION
WDR62-related cognitive consequences may be less severe than expected because 3 out of 11 of the assessed patients had only mild intellectual disability and relatively preserved abilities of autonomy in daily life. We identified progressive ataxia in the second decade of life in one patient, which should encourage clinicians to follow up patients in the long term.
Topics: Adolescent; Ataxia; Cell Cycle Proteins; Child; Child, Preschool; Female; Humans; Intellectual Disability; Male; Microcephaly; Nerve Tissue Proteins; Young Adult
PubMed: 35726608
DOI: 10.1111/dmcn.15060 -
Neuropediatrics Jun 2017
Topics: Humans; Microcephaly
PubMed: 28470649
DOI: 10.1055/s-0037-1602820 -
American Journal of Medical Genetics.... Mar 2023We report a boy with typical clinical features of SHORT syndrome alongside a significant microcephaly and severe developmental delay associated with a de novo single... (Review)
Review
We report a boy with typical clinical features of SHORT syndrome alongside a significant microcephaly and severe developmental delay associated with a de novo single nucleotide missense DNA variant resulting in a single amino acid change in codon 486 of the PIK3R1 gene (PIK3R1 c.1456G>A (p.Ala486Thr)). Our report strikingly coincides with another recently published case from Brazil, describing a 23-year-old woman with the same de novo PIK3R1 DNA variant, who also exhibits SHORT syndrome with severe secondary microcephaly and intellectual disability. On review of the literature, we have identified further cases of PIK3R1-related SHORT Syndrome with a similar phenotype. We note all these cases (including ours) have variants located in the -inter SH2 domain (iSH2); we speculate that pathogenic iSH2 located PIK3R1 variants are associated with a different and otherwise unreported clinical picture of SHORT syndrome that presents with microcephaly and/or significant developmental delay/intellectual disability. The pathogenic mechanism of why these variants apparently lead to a different clinical picture of SHORT syndrome remains unknown.
Topics: Humans; Child; Intellectual Disability; Microcephaly; Hypercalcemia; Nephrocalcinosis; Phenotype; Transcription Factors; Developmental Disabilities
PubMed: 36515361
DOI: 10.1002/ajmg.a.63078 -
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