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Revista de Saude Publica 2022To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with...
OBJECTIVE
To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining.
METHODS
In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables.
RESULTS
In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3).
CONCLUSION
Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.
Topics: Adult; Aged; Brain; Brazil; Cephalometry; Head; Humans; Male; Microcephaly
PubMed: 35649085
DOI: 10.11606/s1518-8787.2022056004175 -
Advances in Experimental Medicine and... 2017Development requires cell proliferation, differentiation and spatial organization of daughter cells to occur in a highly controlled manner. The mode of cell division,... (Review)
Review
Development requires cell proliferation, differentiation and spatial organization of daughter cells to occur in a highly controlled manner. The mode of cell division, the extent of proliferation and the spatial distribution of mitosis allow the formation of tissues of the right size and with the correct structural organization. All these aspects depend on cell cycle duration, correct chromosome segregation and spindle orientation. The centrosome, which is the main microtubule-organizing centre (MTOC) of animal cells, contributes to all these processes. As one of the most structurally complex organs in our body, the brain is particularly susceptible to centrosome dysfunction. Autosomal recessive primary microcephaly (MCPH), primordial dwarfism disease Seckel syndrome (SCKS) and microcephalic osteodysplastic primordial dwarfism type II (MOPD-II) are often connected to mutations in centrosomal genes. In this chapter, we discuss the consequences of centrosome dysfunction during development and how they can contribute to the etiology of human diseases.
Topics: Animals; Biological Evolution; Brain; Centrosome; Disease Models, Animal; Gene Expression Regulation, Developmental; Humans; Microcephaly; Mitosis; Morphogenesis; Species Specificity
PubMed: 28600781
DOI: 10.1007/978-3-319-57127-0_2 -
Nature Feb 2016
Topics: Brazil; Databases, Factual; Disease Outbreaks; Evidence-Based Medicine; Humans; Information Dissemination; Microcephaly; Open Access Publishing; Sequence Analysis, DNA; Time Factors; World Health Organization; Zika Virus; Zika Virus Infection
PubMed: 26863943
DOI: 10.1038/530129a -
International Journal of Environmental... Oct 2016Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden... (Review)
Review
Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.
Topics: Disease Outbreaks; Female; Fetus; Humans; Infant; Latin America; Microcephaly; Pregnancy; Zika Virus; Zika Virus Infection
PubMed: 27775637
DOI: 10.3390/ijerph13101031 -
Current Opinion in Endocrinology,... Feb 2015To review the recent advances in the clinical and molecular characterization of primordial dwarfism, an extreme growth deficiency disorder that has its onset during... (Review)
Review
PURPOSE OF REVIEW
To review the recent advances in the clinical and molecular characterization of primordial dwarfism, an extreme growth deficiency disorder that has its onset during embryonic development and persists throughout life.
RECENT FINDINGS
The last decade has witnessed an unprecedented acceleration in the discovery of genes mutated in primordial dwarfism, from one gene to more than a dozen genes. These genetic discoveries have confirmed the notion that primordial dwarfism is caused by defects in basic cellular processes, most notably centriolar biology and DNA damage response. Fortunately, the increasing number of reported clinical primordial dwarfism subtypes has been accompanied by more accurate molecular classification.
SUMMARY
Qualitative defects of centrioles with resulting abnormal mitosis dynamics, reduced proliferation, and increased apoptosis represent the predominant molecular pathogenic mechanism in primordial dwarfism. Impaired DNA damage response is another important mechanism, which we now know is not mutually exclusive to abnormal centrioles. Molecular characterization of primordial dwarfism is helping families by enabling more reproductive choices and may pave the way for the future development of therapeutics.
Topics: Cell Proliferation; Dwarfism; Facies; Genome-Wide Association Study; Humans; Microcephaly; Mutation; Practice Guidelines as Topic
PubMed: 25490023
DOI: 10.1097/MED.0000000000000121 -
European Journal of Medical Genetics Sep 2014Raine syndrome (RS) is a bone dysplasia characterised by generalised osteosclerosis with periosteal bone formation, characteristic face, and brain abnormalities [MIM #... (Review)
Review
Raine syndrome (RS) is a bone dysplasia characterised by generalised osteosclerosis with periosteal bone formation, characteristic face, and brain abnormalities [MIM # 259775]. Its prevalence is estimated to be < 1/1,000,000. Although it was originally thought always to be lethal, there have now been six reports of patients surviving into childhood and this phenotype is still being defined. The skeletal dysplasia predominantly affects craniofacial development explaining the severe proptosis, underdeveloped midface, depressed nasal bridge and short nose. The main radiological manifestation is a diffuse, marked osteosclerosis of the base of skull and long bones. Raine syndrome is caused by biallelic mutations in FAM20C, located on chromosome 7p22.3. This gene encodes a Golgi casein kinase, which phosphorylates serine residues of extracellular proteins involved in biomineralisation. Facial appearance and radiological findings allow the clinical diagnosis, and molecular testing of FAM20C can confirm this. Desmosterolosis and congenital cytomegalovirus infection may resemble Raine syndrome. If Raine syndrome is suspected prenatally the newborn should be admitted at a neonatal intensive care unit as significant respiratory distress is often present immediately after birth. We present here a review of the pertinent literature in clinical manifestations, molecular background, diagnosis and management.
Topics: Abnormalities, Multiple; Cleft Palate; Diagnosis, Differential; Exophthalmos; Humans; Microcephaly; Osteosclerosis; Prenatal Diagnosis; Prognosis
PubMed: 25019372
DOI: 10.1016/j.ejmg.2014.07.001 -
Child's Nervous System : ChNS :... Jan 2018A relationship between Zika virus (ZikV) infection in pregnancy and the occurrence of microcephaly was established during the Zika outbreak in Brazil (2015-2016).... (Review)
Review
BACKGROUND
A relationship between Zika virus (ZikV) infection in pregnancy and the occurrence of microcephaly was established during the Zika outbreak in Brazil (2015-2016). Neuropathological findings in congenital Zika syndrome helped to understand its pathogenetic mechanisms.
RESULTS
The most relevant postmortem findings in the central nervous system (CNS) of fetuses and neonates infected with ZikV early in gestation are microcephaly with ex-vacuo ventriculomegaly and large head circumference associated with obstructive hydrocephalus due to severe midbrain and aqueduct distortion. Babies with severe brain lesions are born with arthrogryposis. Histologically, there is extensive destruction of the hemispheric parenchyma, calcifications, various disturbances of neuronal migration, reactive gliosis, microglial hyperplasia and occasional perivascular cuffs of lymphocytes, also in the meninges. Hypoplastic lesions secondary to the lack of descending nerve fibers include small basis pontis, pyramids and spinal corticospinal tracts. Cerebellar hypoplasia is also common. Severe nerve motor nerve cell loss is observed in the anterior horn of the spinal cord.
CONCLUSION
A spectrum of neuropathological changes, from severe microcephaly to obstructive hydrocephalus was observed. The severity of the lesions is directly related to the gestational age, the most severe occurring when the mother is infected in the first trimester. Infection of progenitor cells at the germinal matrix was demonstrated. The lack of spinal motor neurons is responsible for fetal acynesia and consequent arthrogryposis.
Topics: Adult; Brain; Brazil; Female; Humans; Infant, Newborn; Microcephaly; Nervous System; Pregnancy; Zika Virus Infection
PubMed: 29167994
DOI: 10.1007/s00381-017-3651-3 -
Cells Jul 2023Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by... (Review)
Review
Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins.
Topics: Humans; Microcephaly; Centrosome; Brain; Brain Diseases; Body Size; Nerve Tissue Proteins; Cell Cycle Proteins
PubMed: 37443841
DOI: 10.3390/cells12131807 -
Trends in Microbiology May 2019After the discovery that Zika virus (ZIKV) could cause microcephaly and other birth defects, we have scrambled to understand how. Now, spreading along with the virus is... (Review)
Review
After the discovery that Zika virus (ZIKV) could cause microcephaly and other birth defects, we have scrambled to understand how. Now, spreading along with the virus is misinformation that a ZIKV mutation is responsible for microcephaly. Putting too much onus on a single mutation could enhance a crisis in India.
Topics: Communication; Female; Humans; India; Microcephaly; Mutation; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Zika Virus; Zika Virus Infection
PubMed: 30826180
DOI: 10.1016/j.tim.2019.02.004 -
Biomedicine & Pharmacotherapy =... Sep 2023Zika virus (ZIKV) poses a serious threat to the entire world. The rapid spread of ZIKV and recent outbreaks since 2007 have caused worldwide concern about the virus.... (Review)
Review
Zika virus (ZIKV) poses a serious threat to the entire world. The rapid spread of ZIKV and recent outbreaks since 2007 have caused worldwide concern about the virus. Diagnosis is complicated because of the cross-reactivity of the virus with other viral antibodies. Currently, the virus is diagnosed by molecular techniques such as RT-PCR and IgM-linked enzyme immunoassays (MAC-ELISA). Recently, outbreaks and epidemics have been caused by ZIKV, and severe clinical symptoms and congenital malformations have also been associated with the virus. Although most ZIKV infections present with a subclinical or moderate flu-like course of illness, severe symptoms such as Guillain-Barre syndrome in adults and microcephaly in children of infected mothers have also been reported. Because there is no reliable cure for ZIKV and no vaccine is available, the public health response has focused primarily on preventing infection, particularly in pregnant women. A comprehensive approach is urgently needed to combat this infection and stop its spread and imminent threat. In view of this, this review aims to present the current structural and functional viewpoints, structure, etiology, clinical prognosis, and measures to prevent this transmission based on the literature and current knowledge. Moreover, we provide thorough description of the current understanding about ZIKV interaction with receptors, and a comparative examination of its similarities and differences with other viruses.
Topics: Adult; Child; Female; Humans; Pregnancy; Zika Virus; Zika Virus Infection; Microcephaly; Disease Outbreaks; Epidemics
PubMed: 37473686
DOI: 10.1016/j.biopha.2023.115175