Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of syndromic and single gene disorders associated with fetal pleural effusion that is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides a comprehensive view of specific and non-specific chromosome aberrations associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of chromosomal abnormalities associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

暂无摘要。

To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical information on the fetus and parents was gathered, and genomic DNAs were extracted from the fetal tissue and family members\' peripheral blood samples. Exome sequencing on fetal DNA was performed and following bioinformatics analysis, the suspected pathogenic variants were confirmed through Sanger sequencing. Prenatal ultrasound performed at 29 weeks of gestation revealed hydrops fetalis, decreased fetal movements, multiple joint contractures and polyhydramnios. Intrauterine fetal death was noted in the third trimester. Exome sequencing revealed compound heterozygous variants in the TTN gene: a paternally inherited allele c.101227C>T (p.Arg33743Ter) and a maternally inherited c.104254C>T (p.Gln34752Ter) allele. These variants have not been previously reported and are evaluated to be likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. We report a fetus with hydrops fetalis and arthrogryposis multiplex congenita associated with a compound heterozygote in the TTN gene. Our report broadens the clinical and genetic spectrum associated with the TTN-related conditions.

BACKGROUND: Acid ceramidase (ACDase) deficiency is an ultrarare autosomal recessive lysosomal disorder caused by pathogenic N-acylsphingosine amidohydrolase (ASAH1) variants. It presents with either Farber disease (FD) or spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME).
OBJECTIVE: The study aims to identify a novel splice site variant in a hydrops fetus that causes ASAH1-related disorder, aid genetic counseling, and accurate prenatal diagnosis.
METHODS: We report a case of hydrops fetalis with a novel homozygous mutation in ASAH1 inherited from non-consanguineous parents. We performed copy number variation sequencing (CNV-Seq) and whole exome sequencing (WES) on the fetus and family, respectively. Minigene splicing analyses were conducted to confirm the pathogenic variants.
RESULTS: WES data revealed a splice site variant of the ASAH1 (c.458-2A>T), which was predicted to affect RNA splicing. Minigene splicing analyses found that the c.458-2A>T variant abolished the canonical splicing of intron 6, thereby activating two cryptic splicing products (c.456_458ins56bp and c.458_503del).
CONCLUSIONS: Overall, we identified a novel splice site variant in the mutational spectrum of ASAH1 and its aberrant effect on splicing. These findings highlight the importance of ultrasonic manifestation and family history of fetal hydrops during ASAH1-related disorders and could also aid genetic counseling and accurate prenatal diagnosis. To the best of our knowledge, this is the shortest-lived account of ASAH1-related disorders in utero with severe hydrops fetalis.

UNASSIGNED: To elaborate the clinical characteristics of congenital pulmonary lymphangiectasia in a neonate with hydrops fetalis. This could be an alert in considering it as a differential diagnosis for neonates with acute respiratory failure.
UNASSIGNED: We reviewed and analyzed single-center registry patients who underwent cadaveric autopsies in the Department of Pathology at Children\'s Hospital from January 1, 2010 to December 31, 2021. We aimed to explore the perinatal clinical manifestations associated with congenital pulmonary lymphangiectasis (CPL). Literature was reviewed to summarize the common features of CPL in pregnancy from individual cases, and to facilitate prenatal and intrapartum diagnosis prognosis, and assessment of medical emergencies.
UNASSIGNED: Thirty-four patients were included, and the main causes of death were intrauterine infection (n = 6), severe pneumonia (n = 11), spontaneous pneumothorax (n = 3), hemorrhagic shock (n = 2), CPL (n = 1), and other non-respiratory failure manifestations (n = 12). The manifestations of respiratory distress in CPL were different from those of intrauterine infections and respiratory failure due to parenchymal lung lesions. These include prenatal presentation of fetal edema, postnatal presentation of uncorrectable respiratory failure with severe hypoproteinemia, pneumothorax and interstitial emphysema on imaging, and poor response to treatment with surfactant-like substances. Thus, when the pregnancy tests reveal fetal edema and postnatal presentation of acute, respiratory distress, the diagnosis of CPL should be considered first, and corresponding medical care should be implemented to improve the survival rate.
UNASSIGNED: CPL is a rare pulmonary defect, and its perinatal clinical manifestations can often be neglected. For children with prenatal fetal edema who die after birth due to progressive respiratory distress, a timely autopsy is of utmost importance to clarify the etiology, improve understanding of CPL, and diagnose early to allow for proper prenatal and postnatal care.

暂无摘要。

OBJECTIVE: This study reviewed and analyzed the prenatal diagnosis experience of thalassemia in our center over the past decade and the abnormal ultrasonic characteristics of fetuses with hemoglobin (Hb) Bart\'s hydrops fetalis.
METHODS: Pregnant women and their partners who tested positive for α0-thalassemia or were diagnosed with thalassemia intermedia (HbH diseases) underwent genetic counseling, and a prenatal diagnostic procedure for α-thalassemia was recommended. Ultrasonography was performed before prenatal diagnosis.
RESULTS: Invasive prenatal α-thalassemia diagnosis and ultrasonography were performed in 1049 patients at risk for Hb Bart\'s hydrops fetalis syndrome at our hospital from 2012 to 2021. Chorionic villus sampling (CVS) was performed in 58 cases (5.5%), amniocentesis in 902 cases (86%), and cordocentesis in 89 cases (8.5%). Hb Bart\'s hydrops fetalis syndrome was diagnosed in 280 fetuses. The most common body cavity effusion was pericardial effusion, ascites, and fetal systemic edema.
CONCLUSIONS: The extensive experience at our center shows that carrier screening, molecular diagnostics, genetic counseling, and prenatal diagnosis are effective measures to prevent Hb Bart\'s hydrops fetalis syndrome. The ultrasonographic abnormalities in fetuses with Hb Bart\'s hydrops are mainly caused by an increase in cardiac output, which leads to the body cavity effusion from various organs.

Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive monogenic disease. However, conventional thalassemia target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart\'s hydrops fetalis and was seeking for prenatal diagnosis during the third pregnancy. Both parents had low level of Hemoglobin A2 indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried -SEA deletion but did not identify any variants in the mother. Multiplex ligation-dependent probe amplification identified a deletion containing two HS-40 probes but could not determine the exact region. Finally, a long-read sequencing (LRS)-based approach directly identified that the exact deletion region was chr16: 48,642-132,584, which was located in the α-globin upstream regulatory elements and named (αα)JM after the Jiangmen city. Gap-PCR and Sanger sequencing confirmed the breakpoint. Both the mother and fetus from the third pregnancy carried heterozygous (αα)JM, and the fetus was normally delivered at gestational age of 39 weeks. This study demonstrated that LRS technology had great advantages over conventional target diagnosis methods for identifying rare thalassemia variants and assisted better carrier screening and prenatal diagnosis of thalassemia.