Prenatal diagnosis of SMPD4 loss - A neurodevelopmental disorder with microcephaly,arthrogryposis and structural brain anomalies

SMPD4 loss is a rare neurodevelopmental disorder that leads to severe mental and physical disability and early death in infancy. Most cases of this genetic condition have been diagnosed postnatally. This article focuses on the prenatal findings of affected fetuses. The phenotypes can include growth restriction, arthrogryposis (clenched hands, foot deformity), as well as cerebral abnormalities (simplified gyral pattern/lissencephaly, cerebellar hypoplasia, corpus callosum deformity). SMPD4 loss is detectable via exome sequencing. Here, two fetuses displayed a homozygotic pathogen variant in the SMPD4 gene, encoding for the enzyme Sphingomyelinase-4. Both parents were heterozygous carriers of the pathogenic variant. On detection of the above mentioned signs exome sequencing is indicated, with focus on the SMPD4 gene.     

冼夫人文化在地方高校传承和发展状况研究

以好心精神为核心的冼夫人文化作为粤西地区的特色文化,与当代社会主义核心价值观相契合。它对大学生进行爱国主义教育、提高人文素质、树立正确的价值观方面有重要的引导作用。以粤西4所高校为例,通过发放问卷的形式对冼夫人文化在高校大学生中的影响进行调查,指出了冼夫人文化在高校传承中存在的问题,并深入了分析在高校思想政治教育工作中如何融入冼夫人文化。     

Prenatal diagnosis of vascular anomalies

Vascular anomalies are rare disorders that encompass a group of lesions characterized by abnormal development of the lymphovascular system. Majority of these anomalies are present at birth and could potentially be detected during the prenatal period on imaging. This allows for early intervention and prompt management to improve outcomes. However, they can be difficult to diagnose, given the rarity and overlapping findings. In this review article, we provide a comprehensive overview of congenital vascular anomalies with a liberal use of images of recent cases at our center emphasizing prenatal imaging findings and the natural history of these conditions.     

Prenatal molecular diagnosis in RASA1-related disease

RASA1-related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1-related diseases. This first report of prenatal diagnosis in RASA1-related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.     

Prenatal diagnosis of congenital toxoplasmosis

Ninety-three pregnant women with Toxoplasma gondii seroconversion during pregnancy underwent prenatal diagnosis of fetal toxoplasmosis. The following tests were used: (1) amniocentesis for mouse inoculation (93 subjects), (2) amplification of T. gondii DNA by polymerase chain reaction (PCR) (79 subjects), and (3) cordocentesis for the detection of T. gondii-specific IgM antibodies (13 subjects). All patients had serial ultrasonographic scans to detect those fetuses with abnormalities that could be associated with congenital toxoplasmosis. Eighteen pregnancies (19.4%) had evidence of vertical transmission. A total of 11/18 (61.1%) had positive amniotic mouse inoculation test, while 10/12 (83.3%) had positive PCR results. The combination of both tests allowed the prenatal diagnosis in 17/18 infected fetuses (94.4%). All patients who underwent cordocentesis for the detection of T. gondii-specific IgM antibodies had negative results. However, in two of the above cases fetal toxoplasmosis was detected by amniotic fluid studies. In five of the infected fetuses there were abnormal ultrasonographic findings. All pregnancies with evidence of vertical transmission were terminated, whereas the remaining pregnancies proceeded normally to term. The present data showed that amniotic fluid studies, preferably PCR amplification of T. gondii DNA, are the best diagnostic tools for the detection of vertical transmission in pregnancies with seroconversion during pregnancy. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal ultrasonographic diagnosis of congenital megalourethra

Congenital megalourethra is a rare genital anomaly characterized by dilatation of the penile urethra without evidence of distal obstruction. Reports of the prenatal diagnosis of this condition in the literature are limited. We present a case of congenital megalourethra with obstructive uropathy from the posterior urethra diagnosed prenatally at 18 weeks of gestation. ‘Prune-belly’-like features, colonic malrotation, and imperforate anus were also found on autopsy.     

Prenatal diagnosis of Lesch-Nyhan syndrome: Experience with three fetuses at risk

Our experience with the prenatal detection of the Lesch-Nyhan syndrome (LNS; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency) in three fetuses at risk is reported. Enzyme activities were measured in cultured amniocytes in two pregnancies, and in tissues and cultures obtained from chorionic villus sampling (CVS) in a third pregnancy. In all tissues the specific activities of HGPRT and adenine phosphoribosyltransferase (APRT) were determined and APRT/HGPRT ratios were calculated. In addition to the enzyme assays, the rate of purine synthesis de novo was assessed in the two amniocyte cultures, and the rate of [¹⁴C]hypoxanthine incorporation into nucleotides and sensitivity to azaguanine were measured in one of the amniocyte cultures. We report the diagnosis of normal fetuses by study of amniocytes in two pregnancies and of LNS using CVS in one pregnancy. In all three cases the diagnosis was confirmed.     

Prenatal diagnosis of congenital human cytomegalovirus infection

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16–30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases and ⩾ 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.     

Prenatal diagnosis of congenital gastric outlet obstruction

A case of gastric outlet obstruction diagnosed prenatally at 22 weeks' gestation is described. The differential diagnosis and the clinical management of this rare condition are discussed, and an updated literature review is presented.     

Prenatal diagnosis of Fukuyama congenital muscular dystrophy

Fukuyama congenital muscular dystrophy (FCMD) is characterized by infantile hypotonia, symmetrical generalized muscle weakness, and neuronal migration disturbances that result in changes consistent with cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia. FCMD is recognized as an autosomal recessive genetic defect. Genetic counselling is recommended for parents at risk of having a child with FCMD. Given the high risk and overwhelming prospect of having another child with this incurable devastating condition leads many couples to consider prenatal diagnosis. In Japanese families, haplotype analysis using microsatellite markers is available. In non-Japanese families, DNA sequence analysis is available. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Milroy's primary congenital lymphedema

Milroy's primary congenital lymphedema (PCL) (hereditary lymphedema type I, Milroy disease) is present at birth, and mostly affects the dorsal aspects of feet. It is mostly a life-long condition but does not affect longevity. Complications are rare except for chronic discomfort and warmness of affected areas. PCL is an autosomal dominant disease with incomplete penetrance due to a mutation in the gene locus encoding for VEGFR3 with resultant dysgenesis of microlymphatic vessels. We report on two fetuses where ultrasonographic examination at 15 weeks of gestation showed significant edema of the dorsal aspects of both feet with no evidence of other major malformations. Whereas in one fetus the edema resolved completely, it persisted in the second fetus and proved after birth to be of lymphedematous nature. To the best of our knowledge, this is the first report of early prenatal diagnosis of primary congenital lymphedema via fetal ultrasonographic examination and of spontaneous resolution of lymphedema during fetal life. Copyright © 2002 John Wiley & Sons, Ltd.