Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the t...Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p<sup>21</sup>, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.展开更多
Introduction: Ventriculomegaly is one of the most common abnormalities detected by prenatal ultrasound. This entity can be associated with brain abnormalities and other malformations. In order to perform a good prenat...Introduction: Ventriculomegaly is one of the most common abnormalities detected by prenatal ultrasound. This entity can be associated with brain abnormalities and other malformations. In order to perform a good prenatal counseling, the diagnosis is essential. Objective: Our purpose was to report the management of 3 cases of ventriculomegaly in our practice and underline the benefits of the neuropathologic exam. Methods: We analyzed retrospectively 3 medical files concerning fetus that were diagnosed as having one or two ventricles of >10 mm and a follow up for prenatal diagnosis. Results: All cases were diagnosed between 22 and 27 weeks of gestation by an ultrasound. In a case, the ventriculomegaly evolved rapidly to a hydrocephalus. In two cases, the pregnancy was terminated with medical interruption by the parent’s request. Amniocentesis confirmed the diagnosis of congenital toxoplasmosis in case 2 there were no chromosomal abnormalities after karyotyping. Causes included holoprosencephaly, congenital toxoplasmosis and mesencephalosynapsis. Conclusion: Ultrasonography may detect ventriculomegaly nerverthless in the cases presented, pathology exam was essential to assess the diagnostic. Causes are numerous and prognosis variable. We recommand MRI that is more and more accessible in our regions in the follow up of this entity and neuropathology exam in case of termination of the pregnancy. The establishment of main causes of ventriculomegaly in our regions (infectious causes for example) could help to prevent this outcome in our practice.展开更多
Background:Chromosomal abnormalities are important causes of ventriculomegaly(VM).In mild and isolated cases of fetal VM,obstetricians rarely give clear indications for pregnancy termination.We aimed to calculate the ...Background:Chromosomal abnormalities are important causes of ventriculomegaly(VM).In mild and isolated cases of fetal VM,obstetricians rarely give clear indications for pregnancy termination.We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis(CMA)in VM,providing more information on genetic counseling and prognostic evaluation for fetuses with VM.Methods:The Chinese language databases Wanfang Data,China National Knowledge Infrastructure,and China Biomedical Literature Database(from January 1,1991 to April 29,2020)and English language databases PubMed,Embase,and Cochrane Library(from January 1,1945 to April 29,2020)were systematically searched for articles on fetal VM.Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging(MRI)assessment of lateral ventricular atrium width:≥10 to<15 mm for mild VM,and≥15 mm for severe VM.Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI.R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM,and the combined rate and 95%confidence interval(CI)were calculated.Results:Twenty-three articles involving 1635 patients were included.The incidence of chromosomal abnormalities in VM was 9%(95%CI:5%-12%)and incremental yield of CMA in VM was 11%(95%CI:7%-16%).The incidences of chromosomal abnormalities in mild,severe,isolated,and non-isolated VM were 9%(95%CI:4%-16%),5%(95%CI:1%-11%),3%(95%CI:1%-6%),and 13%(95%CI:4%-25%),respectively.Conclusions:Applying CMA in VM improved the detection rate of abnormalities.When VM is confirmed by ultrasound or MRI,obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities.Moreover,CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis.CMA cannot completely replace chromosome karyotype analysis.展开更多
Objective::To assess the value of magnetic resonance imaging(MRI)in fetal lateral ventriculomegaly diagnosed with ultrasound,and to study the relationship between the degree of isolated lateral ventriculomegaly and ne...Objective::To assess the value of magnetic resonance imaging(MRI)in fetal lateral ventriculomegaly diagnosed with ultrasound,and to study the relationship between the degree of isolated lateral ventriculomegaly and neonatal prognosis.Methods::The pregnancy information and outcomes of 97 cases of fetal ventriculomegaly were retrospectively reviewed in the Tianjin Central Hospital of Gynecology Obstetrics from January 2016 to December 2017.The maternal age was 18-42 years,and the fetal gestational age at diagnosis was 19+4 to 37+3 weeks.MRI and ultrasound were used to compared the diagnosis of fetal lateral ventriculomegaly and evaluated the development of the nervous system after birth.Results::Among 97 pregnancy cases,associated central nervous system malformations were observed in 36 cases on ultrasound or ultrasound+MRI.Central nervous system malformations were diagnosed with ultrasound in 15 cases(15/36,41.7%)and with ultrasound+MRI in 25 cases(25/36,69.4%).Pearsonχ2 test was used to compare the detection rates between the groups,and the difference was statistically significant(P<0.05).We followed up 61 cases of isolated lateral ventriculomegaly for 1-3 years after birth.According to the width of the lateral ventricle of the fetus in middle pregnancy,the subjects were grouped as follows:mild 33 cases(lateral ventricle width 10.0-12.0 mm),moderate 23 cases(lateral ventricle width 12.1-15.0 mm),and severe 5 cases(lateral ventricle width>15.0 mm).The rate of normal growth and development in the mild group was 90.9%(30/33),that in the moderate group was 69.6%(16/23),and that in the severe group was 40.0%(2/5),and the difference between groups was statistically significant(P<0.05).Conclusion::Ultrasound combined with MRI can detect more central nervous system malformations,and the degree of isolated lateral ventriculomegaly is closely related to fetal prognosis.展开更多
文摘Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p<sup>21</sup>, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.
文摘Introduction: Ventriculomegaly is one of the most common abnormalities detected by prenatal ultrasound. This entity can be associated with brain abnormalities and other malformations. In order to perform a good prenatal counseling, the diagnosis is essential. Objective: Our purpose was to report the management of 3 cases of ventriculomegaly in our practice and underline the benefits of the neuropathologic exam. Methods: We analyzed retrospectively 3 medical files concerning fetus that were diagnosed as having one or two ventricles of >10 mm and a follow up for prenatal diagnosis. Results: All cases were diagnosed between 22 and 27 weeks of gestation by an ultrasound. In a case, the ventriculomegaly evolved rapidly to a hydrocephalus. In two cases, the pregnancy was terminated with medical interruption by the parent’s request. Amniocentesis confirmed the diagnosis of congenital toxoplasmosis in case 2 there were no chromosomal abnormalities after karyotyping. Causes included holoprosencephaly, congenital toxoplasmosis and mesencephalosynapsis. Conclusion: Ultrasonography may detect ventriculomegaly nerverthless in the cases presented, pathology exam was essential to assess the diagnostic. Causes are numerous and prognosis variable. We recommand MRI that is more and more accessible in our regions in the follow up of this entity and neuropathology exam in case of termination of the pregnancy. The establishment of main causes of ventriculomegaly in our regions (infectious causes for example) could help to prevent this outcome in our practice.
文摘Background:Chromosomal abnormalities are important causes of ventriculomegaly(VM).In mild and isolated cases of fetal VM,obstetricians rarely give clear indications for pregnancy termination.We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis(CMA)in VM,providing more information on genetic counseling and prognostic evaluation for fetuses with VM.Methods:The Chinese language databases Wanfang Data,China National Knowledge Infrastructure,and China Biomedical Literature Database(from January 1,1991 to April 29,2020)and English language databases PubMed,Embase,and Cochrane Library(from January 1,1945 to April 29,2020)were systematically searched for articles on fetal VM.Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging(MRI)assessment of lateral ventricular atrium width:≥10 to<15 mm for mild VM,and≥15 mm for severe VM.Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI.R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM,and the combined rate and 95%confidence interval(CI)were calculated.Results:Twenty-three articles involving 1635 patients were included.The incidence of chromosomal abnormalities in VM was 9%(95%CI:5%-12%)and incremental yield of CMA in VM was 11%(95%CI:7%-16%).The incidences of chromosomal abnormalities in mild,severe,isolated,and non-isolated VM were 9%(95%CI:4%-16%),5%(95%CI:1%-11%),3%(95%CI:1%-6%),and 13%(95%CI:4%-25%),respectively.Conclusions:Applying CMA in VM improved the detection rate of abnormalities.When VM is confirmed by ultrasound or MRI,obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities.Moreover,CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis.CMA cannot completely replace chromosome karyotype analysis.
基金Early pregnancy screening combined with high-through-put sequencing technology in the diagnosis of birth defects(17YFZCSY00830)Study on the interference factors of non-invasive detection accuracy of fetal aneuploid(18ZXDBSY00230)
文摘Objective::To assess the value of magnetic resonance imaging(MRI)in fetal lateral ventriculomegaly diagnosed with ultrasound,and to study the relationship between the degree of isolated lateral ventriculomegaly and neonatal prognosis.Methods::The pregnancy information and outcomes of 97 cases of fetal ventriculomegaly were retrospectively reviewed in the Tianjin Central Hospital of Gynecology Obstetrics from January 2016 to December 2017.The maternal age was 18-42 years,and the fetal gestational age at diagnosis was 19+4 to 37+3 weeks.MRI and ultrasound were used to compared the diagnosis of fetal lateral ventriculomegaly and evaluated the development of the nervous system after birth.Results::Among 97 pregnancy cases,associated central nervous system malformations were observed in 36 cases on ultrasound or ultrasound+MRI.Central nervous system malformations were diagnosed with ultrasound in 15 cases(15/36,41.7%)and with ultrasound+MRI in 25 cases(25/36,69.4%).Pearsonχ2 test was used to compare the detection rates between the groups,and the difference was statistically significant(P<0.05).We followed up 61 cases of isolated lateral ventriculomegaly for 1-3 years after birth.According to the width of the lateral ventricle of the fetus in middle pregnancy,the subjects were grouped as follows:mild 33 cases(lateral ventricle width 10.0-12.0 mm),moderate 23 cases(lateral ventricle width 12.1-15.0 mm),and severe 5 cases(lateral ventricle width>15.0 mm).The rate of normal growth and development in the mild group was 90.9%(30/33),that in the moderate group was 69.6%(16/23),and that in the severe group was 40.0%(2/5),and the difference between groups was statistically significant(P<0.05).Conclusion::Ultrasound combined with MRI can detect more central nervous system malformations,and the degree of isolated lateral ventriculomegaly is closely related to fetal prognosis.
