Humans ; Female ; Hydrops Fetalis/genetics* ; Ion Channels/genetics*

A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.
Infant, Newborn ; Male ; Humans ; Female ; Pregnancy ; Hydrops Fetalis/genetics* ; N-Acetylneuraminic Acid ; Placenta/pathology* ; Ascites

INTRODUCTIONRecurrent non-immune fetal hydrops (NIH) has been reported in the literature but is a rare entity, with fewer than 6 reported cases so far. It has been postulated to be related to a recessive gene.

CLINICAL PICTUREWe report a case of recurrent fetal hydrops in a multigravida with no medical history of note. She presented in her current pregnancy with a significant history of having 4 (out of 7) previous pregnancies affected by hydrops.

TREATMENTAll the affected pregnancies resulted in mid-trimester pregnancy termination (MTPT) following diagnosis in the second trimester. Previous investigations for hydrops did not yield any obvious cause.

OUTCOMEHer most recent pregnancy was unaffected. We discuss the possible differential diagnoses and the likelihood of autosomal recessive metabolic diseases being the aetiological factor.

CONCLUSIONRare causes of fetal hydrops need to be excluded in cases of recurrent non-immune hydrops with no obvious aetiology following routine investigations.

Abortion, Legal ; Adult ; Diagnosis, Differential ; Female ; Humans ; Hydrops Fetalis ; diagnosis ; genetics ; immunology ; Pregnancy ; Prenatal Diagnosis ; Recurrence ; Thalassemia

OBJECTIVE: To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus. METHODS: DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing. RESULTS: The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c.481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother. CONCLUSION Barth syndrome due to the c.481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.
Barth Syndrome ; genetics ; Cardiomyopathy, Dilated ; genetics ; Echocardiography ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Hydrops Fetalis ; genetics ; Male ; Mutation ; Pregnancy ; Transcription Factors ; genetics

OBJECTIVE: To explore the genetic basis of three families with recurrence of non-immune hydrops fetalis (NIHF) but negative result by copy number variation sequencing (CNV-seq). METHODS: Amniotic fluid sample and/or abortive tissues of the fetuses were collected and subjected to CNV-seq analysis. Peripheral blood samples of the parents were also taken for trio whole exome sequencing (trio WES). RESULTS: Fetus 1 was found to harbor heterozygous c.976G>T(p.Glu326*) variant of the SOX18 gene in addition with compound heterozygous variants c.844C>T(p.Arg282Trp) and c.9472+1G>A of the RYR1 gene. The three variants were all inherited from its parents and have been associated with the etiology of NIHF. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.976G>T variant of SOX18 gene and c.9472+1G>A of RYR1 gene were predicted to be pathogenic (PVS1+PM2+PP3+PP4, PVS1+PM2+PP3), and c.844C>T variant of RYR1 gene to be likely pathogenic (PM1+PM2+PP3). Fetus 2 was found to harbor compound heterozygous variants c.6682C>T(p.Gln2228*) and c.4373_4383del(p.Val1458Alafs*63) of the PIEZO1 gene. Both variants were also inherited from its parents and are associated with the etiology of NIHF. Based on ACMG standards and guidelines, both c.6682C>T and c.4373_4383del variants of PIEZO1 gene were predicted to be pathogenic (PVS1+PM2+PP4, PVS1+PM2). Fetus 3 was found to harbor compound heterozygous variants of the TTN gene c.29860G>C(p.Asp9954His) and c.21107A>T(p.Asp7036Val), which were respectively inherited from its parents. Both variants have been strongly associated with the phenotype, though the connection between the etiology of NIHF and variants of the TTN gene remains elusive. Based on ACMG standards and guidelines, the c.29860G>C and c.21107A>T variants of TTN gene were predicted to be likely pathogenic (PM1+PM2+PP3). CONCLUSION Trio WES can improve the diagnosis rate of NIHF with a negative result by CNV-seq. Considering the urgency of prenatal diagnosis, CNV-seq and trio WES should be carried out at the same time for fetuses with NIHF.
DNA Copy Number Variations ; Female ; Genomics ; Heterozygote ; Humans ; Hydrops Fetalis/genetics* ; Ion Channels ; Pregnancy ; SOXF Transcription Factors ; United States ; Whole Exome Sequencing

INTRODUCTIONWe report the fi rst successful preimplantation genetic diagnosis (PGD) for Hb Bart's hydrops fetalis in Singapore, involving both fresh and frozen embryo replacement cycles.

CLINICAL PICTURETwo couples who were carriers of the Southeast Asian type double gene deletion (--(SEA) deletion carriers) requested for PGD. Couple A had 2 previous affected pregnancies, while couple B have a child of unknown genotypic status.

TREATMENTOne PGD cycle was performed for each couple. The --(SEA) deletion was detected using a gap-PCR strategy. Couple A had 1 fresh-embryo replacement cycle while couple B underwent 2 frozen-embryo replacement cycles.

OUTCOMECouple A achieved a twin pregnancy. Second trimester complications resulted in premature delivery, where 1 baby girl survived. Couple B achieved a singleton pregnancy resulting in delivery of a healthy baby boy. Genotype analysis of all babies confirmed the PGD results consistent with clinically unaffected status.

CONCLUSIONSWe have successfully performed PGD to avoid Hb Bart's hydrops fetalis syndrome.

Adult ; Embryo Transfer ; Female ; Genetic Carrier Screening ; Genetic Testing ; Hemoglobins, Abnormal ; Humans ; Hydrops Fetalis ; diagnosis ; genetics ; prevention & control ; Male ; Minisatellite Repeats ; genetics ; Ovulation Induction ; methods ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Hematologic ; diagnosis ; genetics ; prevention & control ; Preimplantation Diagnosis ; Singapore ; Sperm Injections, Intracytoplasmic ; alpha-Globins ; genetics