Mosaic tetrasomy 9p at amniocentesis: Prenatal diagnosis,molecular cytogenetic characterization,and literature review

ObjectiveThis study was aimed at prenatal diagnosis of mosaic tetrasomy 9p and reviewing the literature.Materials and methodsA 37-year-old woman underwent amniocentesis at 20 weeks' gestation because of advanced maternal age and fetal ascites. Cytogenetic analysis of cultured amniocytes revealed 21.4% (6/28 colonies) mosaicism for a supernumerary i(9p). Repeat amniocentesis was performed at 23 weeks' gestation. Array comparative genomic hybridization, interphase fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction were applied to uncultured amniocytes, and conventional cytogenetic analysis was applied to cultured amniocytes.ResultsArray comparative genomic hybridization analysis of uncultured amniocytes detected a genomic gain at 9p24.3–9q21.11. Interphase fluorescence in situ hybridization analysis of uncultured amniocytes using a 9p24.3-specific probe RP11-31F19 (spectrum red) showed four red signals in 47.1% (49/104 cells) in uncultured amniocytes. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX, +idic(9)(pter→q21.11::q21.11→pter)[4]/46,XX[20] and 16.7% (4/24 colonies) mosaicism for tetrasomy 9p. Quantitative fluorescent polymerase chain reaction confirmed a maternal origin of tetrasomy 9p. The pregnancy was terminated, and a malformed fetus was delivered with hydrops fetalis and facial dysmorphism. The fetal blood cells had 32.5% (13/40 cells) mosaicism for tetrasomy 9p.ConclusionMosaic tetrasomy 9p at amniocentesis can be associated with fetal ascites and hydrops fetalis. The mosaic level of tetrasomy 9p may decrease after long-term tissue culture in amniocytes in case of mosaic tetrasomy 9p.     

A novel nonsense mutation of TGFBR1 in a fetus with untypical Loeys-Dietz syndrome 1

ObjectiveWe present a rare untypical Loeys-Dietz syndrome 1 case in prenatal setting and report a novel mutation in the TGFBR1 gene.Case reportA pregnant woman came for medical attention due to the fetal ultrasound anomaly. The fetus was found to have short long bones. Trio-based WES was applied to the family. A novel de novo nonsense mutation c.1237C > T was detected in the TGFBR1 gene. A diagnosis of Loeys-Dietz syndrome 1 (LDS1) was plausible, but the fetus did not demonstrate the characteristic phenotype of the syndrome.ConclusionIn prenatal setting, fetal phenotypes are difficult to be fully observed, putting stress on the utility of molecular techniques. LDS1 in fetuses could present untypical features such as skeletal dysplasia.     

Hydrops fetalis with cystic hygroma: A case report

Hydrops fetalis is an excess accumulation of fluid in the fetus. Depending on the severity and cause of hydrops, there may be edema of fetus and placenta, ascites, pleural effusions and/or pericardial effusions. In previous years, most cases of hydrops were caused by severe erythroblastosis fetalis secondary to Rh isoimmunization. Most cases of hydrops fetalis are now caused by other conditions and are known as nonimmune hydrops. Here is a case of an 18 week pregnancy with hydrops fetalis, cystic hygroma and other structural anomalies suggestive chromosomal abnormalities.     

Novel prenatally diagnosed compound heterozygous POMT2 variants in fetal congenital primary aqueduct stenosis

ObjectiveTo study the etiology of congenital hydrocephalus in genetic aqueduct stenosis.Case reportWe report the case of a 31-year-old pregnant female, G2P0A1, with a history of hyperthyroidism under medical control. The patient received regular prenatal care, with no specific findings in the Level II ultrasound at 21 weeks of gestation. However, hydrocephalus was noted at GA 31 weeks. High-resolution sonography and fetal magnetic resonance imaging (MRI) reported fetal aqueduct stenosis. Maternal HSV, CMV, and toxoplasma infection were not detected. Fetal karyotype and chromosomal microarray analysis (CMA) indicated a normal. After intensive counseling, the parents decided to terminate the pregnancy due to the poor fetal prognosis. Post-mortem, a whole-exome sequencing (WES) and Sanger sequencing analysis trio study identified two compound heterozygous variants in the POMT2 gene inherited from both recessive parents. In the subsequent pregnancy, a WES survey revealed inheritance of only the maternal POMT2 gene variant; a live, healthy male baby was born.ConclusionExtended WES represents a precision maternal medicine tool for novel prenatal diagnosis of congenital aqueduct stenosis.     

Prenatally diagnosed microdeletion in the TCOF1 gene in fetal congenital primary Treacher Collins Syndrome

ObjectiveTo study prenatal diagnosis of congenital Treacher Collins syndrome, an etiology of craniofacial abnormalities.Case reportWe present a case of fetal craniofacial abnormalities identified by antepartum sonography screening in the third trimester (28 weeks); features of micrognathia, hypoplastic zygomatic arches and bilateral low-set microtia were detected. Due to the unknown severity of the craniofacial abnormalities and poor prognosis, the parents decided to terminate the fetus after through counselling. A normal female karyotype was detected. The parents consented to chromosome microarray analysis (CMA), which identified a de novo mutation of the TCS1 gene locus on chromosome 5.ConclusionMolecular CMA is an effective tool for prenatal diagnosis of congenital craniofacial abnormalities associated with Treacher Collins syndrome.     

Alpha thalassaemia hydrops fetalis in the UK: the importance of screening pregnant women of Chinese, other South East Asian and Mediterranean extraction for alpha thalassaemia trait.

OBJECTIVE: Alpha zero (alpha 0 or alpha-1) thalassaemia is an important genetic risk for women originating from Hong Kong, Singapore, Vietnam, Thailand, the Philippines or South China. Cypriots are also at risk. Carriers of alpha zero thalassaemia trait can be detected by routine haemoglobinopathy screening. When a couple are both carriers, in each pregnancy there is a 25% risk that the fetus will have alpha thalassaemia hydrops fetalis; this is fatal for the fetus and carries serious obstetric and psychological risks for the mother. Most informed couples at risk request prenatal diagnosis and selective abortion. This study investigates the effectiveness of screening, counselling and prenatal diagnosis for alpha thalassaemia hydrops fetalis in the UK. DESIGN: Retrospective analysis of the notes. SUBJECTS: 18 couples attending University College Hospital London for prenatal diagnosis of alpha thalassaemia hydrops fetalis since 1982. RESULTS: The study shows underdiagnosis of both alpha zero thalassaemia trait and alpha thalassaemia hydrops fetalis leading to avoidable stillbirths and complications in pregnancy. CONCLUSION: We recommend early screening for alpha zero thalassaemia trait for all women of Southeast Asian or eastern Mediterranean origin and the offer of prenatal diagnosis when indicated. The diagnosis of alpha thalassaemia hydrops fetalis should be considered in women of the relevant ethnic origin who have a stillbirth, neonatal death, abnormal ultrasound findings at fetal anomaly scanning (especially a large placenta), or who develop pre-eclampsia.     

Etiology and outcome of hydrops fetalis

Objectives : To identify the etiology and pregnancy outcome of hydrops fetalis in a cohort of pregnancies referred to a tertiary maternal fetal medicine center in the UK. These data allow the review of a large series of pregnancies affected by hydrops fetalis and emphasize the importance of investigation and then treatment of individual cases. This provides parents with improved information and especially specific prognostic information. Methods : A retrospective review of 63 consecutive cases of hydrops fetalis managed between September 1996 and March 1999. Results : Of the pregnancies, 12.7% ( n = 8) were associated with an 'immune' etiology. Of these, 62.5% ( n = 5) had fetal anemia due to anti-D, 25% ( n = 2) anti-Kell and 12.5% ( n = 1) anti-c antibodies. The remaining 55 cases (87.3%) had a non-immune cause. Eight (14.5%) were due to human parvovirus B19 infection. Fourteen cases (25.5%) were associated with aneuploidy and, in four (7.3%), a primary hydrothorax was the cause of the non-immune hydrops fetalis. A cardiac cause was found in five (9.1%) cases. Three of these had supraventricular tachycardia and one had congenital complete heart block. Cystic hygroma was associated with hydrops fetalis in six cases. Twin-twin transfusion syndrome was the cause for hydrops in two cases. Massive transplacental hemorrhage was identified in one case. Fetal akinesia and muscular dystrophy caused hydrops in one case each. In 14.5% (8/55) of cases no obvious cause was identified and these were classified as 'idiopathic'. Three other cases could not be classified because parents declined investigations (unclassified). In the pregnancies with non-immune hydrops fetalis, the outcome was favorable in 27.3% (15/55) of cases. Conclusion : The prognosis of hydrops fetalis differs markedly between different etiological groups. Etiologies range from treatable causes with a good outcome and probably no long-term side-effects (as in case of parvovirus B19), to others which are incompatible with life or are associated with considerable perinatal morbidity and mortality.     

镜像综合征18例临床分析

目的:探讨镜像综合征的临床诊断、治疗和预后。方法:回顾性分析18例镜像综合征的临床经过、实验室检查、并发症和母儿结局。结果:(1)本研究18例镜像综合征胎儿水肿的原因:13例为Hb Bart's水肿胎,2例胎儿存在复杂心脏畸形,1例双胎输血综合征(TTTS),1例细小病毒B19感染,1例胎儿水肿原因不明。(2)18例镜像综合征均出现母体水肿-胎儿水肿-胎盘水肿三联征。18例镜像综合征患者最常见的母体症状是母体水肿(100%),其次是低蛋白血症(94.4%),血液稀释(94.4%),轻中度贫血(94.4%),蛋白尿(88.9%),尿酸升高(88.9%),高血压(55.6%),肌酐升高(33.3%),乳酸脱氢酶升高(27.8%),血小板减少(16.7%),头痛(11.1%),肝酶轻度升高(5.6%)和少尿(5.6%)。(3)孕产妇并发症有产后出血、胎盘粘连、胎盘早剥、弥漫性血管内凝血(DIC)、心衰、HELLP综合征、急性肺水肿和急性肾功能衰竭。无一例孕妇死亡,但仅获2个预后良好的新生儿。结论:伴随胎儿水肿或胎盘水肿出现母体水肿,即可确诊镜像综合征,镜像综合征可能严重威胁母婴预后,诊断镜像综合征后,应尽可能地查找和纠正胎儿水肿的原因,但是如果不能找到或无法纠正导致胎儿水肿的特定原因,为减少母婴危害,应及时终止妊娠。     

Detection of a familial 1q21.1 microdeletion and concomitant CHD1L mutation in a fetus with oligohydramnios and bilateral renal dysplasia on prenatal ultrasound

ObjectiveWe present detection of a familial 1q21.1 microdeletion and concomitant CHD1L mutation in a fetus with oligohydramnios and bilateral renal dysplasia on prenatal ultrasound.Case reportA 37-year-old, primigravid woman was referred for level II ultrasound examination at 16 weeks of gestation because of oligohydramnios. The parents were phenotypically normal, and there were no congenital malformations in the family. Prenatal ultrasound at 17 weeks of gestation revealed a fetus with fetal growth biometry equivalent to 16 weeks, oligohydramnios with an amniotic fluid index (AFI) of 1.4 cm and bilateral renal dysplasia without sonographic demonstration of bilateral renal arteries. The pregnancy was subsequently terminated, and a 137-g fetus was delivered without characteristic facial dysmorphism. Postnatal cytogenetic analysis of the umbilical cord and parental bloods revealed normal karyotypes. However, array comparative genomic hybridization (aCGH) analysis on the DNA extracted from the umbilical cord revealed a 2.038-Mb microdeletion of 1q21.1-q21.2 encompassing 11 [Online Mendelian Inheritance in Man (OMIM)] genes of PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, GPR89B, NBPF14, TRN-GTT2-1 and NBPF20. The mother was found to carry the same microdeletion. A missense mutation of c.2353T > G, p.Ser785Ala in CHD1L was detected in the umbilical cord. The father was found to carry a heterozygous mutation of c.2353T > G, p.Ser785Ala in CHD1L.ConclusionFetuses with a 1q21.1 microdeletion and concomitant CHD1L mutation may present oligohydramnios and bilateral renal dysplasia on prenatal ultrasound.     

Etiology and outcome of hydrops fetalis.

OBJECTIVES: To identify the etiology and pregnancy outcome of hydrops fetalis in a cohort of pregnancies referred to a tertiary maternal fetal medicine center in the UK. These data allow the review of a large series of pregnancies affected by hydrops fetalis and emphasize the importance of investigation and then treatment of individual cases. This provides parents with improved information and especially specific prognostic information. METHODS: A retrospective review of 63 consecutive cases of hydrops fetalis managed between September 1996 and March 1999. RESULTS: Of the pregnancies, 12.7% (n = 8) were associated with an 'immune' etiology. Of these, 62.5% (n = 5) had fetal anemia due to anti-D, 25% (n = 2) anti-Kell and 12.5% (n = 1) anti-c antibodies. The remaining 55 cases (87.3%) had a non-immune cause. Eight (14.5%) were due to human parvovirus B19 infection. Fourteen cases (25.5%) were associated with aneuploidy and, in four (7.3%), a primary hydrothorax was the cause of the non-immune hydrops fetalis. A cardiac cause was found in five (9.1%) cases. Three of these had supraventricular tachycardia and one had congenital complete heart block. Cystic hygroma was associated with hydrops fetalis in six cases. Twin-twin transfusion syndrome was the cause for hydrops in two cases. Massive transplacental hemorrhage was identified in one case. Fetal akinesia and muscular dystrophy caused hydrops in one case each. In 14.5% (8/55) of cases no obvious cause was identified and these were classified as 'idiopathic'. Three other cases could not be classified because parents declined investigations (unclassified). In the pregnancies with non-immune hydrops fetalis, the outcome was favorable in 27.3% (15/55) of cases. CONCLUSION: The prognosis of hydrops fetalis differs markedly between different etiological groups. Etiologies range from treatable causes with a good outcome and probably no long-term side-effects (as in case of parvovirus B19), to others which are incompatible with life or are associated with considerable perinatal morbidity and mortality.     

Prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta associated with unaffected parents and paternal gonadal mosaicism

ObjectiveTo present the prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta (OI) associated with unaffected parents and paternal gonadal mosaicism.Materials and MethodsA 37-year-old woman was referred for genetic counseling at 18 weeks of gestation because of advanced maternal age and a family history of OI. The woman had a daughter who was affected with OI type III and carried an insertion frameshift mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. The woman and her husband were non-consanguineous and healthy. Amniocentesis was performed at 18 weeks of gestation.ResultsCytogenetic analysis revealed a karyotype of 46,XX. Molecular analysis of the amniocytes revealed a recurrent mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. Mutational analysis of the family revealed no mutation of the COL1A1 gene in the parental bloods. However, mosaicism for the COL1A1 mutation was found in the paternal sperms. Level II ultrasound examination showed a curved right tibia, a narrow chest with irregular ribs and mild frontal bossing in the fetus. The parents decided to terminate the pregnancy, and a female fetus was delivered at 23 weeks of gestation with curved long bones.ConclusionRecurrent autosomal dominant OI may occur in the offspring of unaffected parents with parental gonadal mosaicism. Genetic counseling of recurrent autosomal dominant OI should include a thorough mutational analysis of the family members, and mutational analysis of the sperm may detect paternal gonadal mosaicism for the mutation.     

Lethal arthrogryposis with icthyosis: overlap with Neu-Laxova syndrome, restrictive dermopathy and harlequin fetus

We describe a stillborn female with joint contractures, subcutaneous oedema, ectropion, a severely flattened nose, an 'O' shaped open mouth and extensive peeling of skin. The head circumference was normal. She was born at 33 weeks of gestation to consanguineous parents, who had one previous offspring affected with non-immune hydrops fetalis. Pathological, radiological and prenatal findings are reported. The features of the present case are compared with those of Neu-Laxova syndrome, restrictive dermopathy and harlequin fetus.     

Prenatal diagnosis by whole exome sequencing in a family with a novel TBR1 mutation causing intellectual disability

ObjectiveTo provide prenatal diagnosis for a pregnant woman with genetic history of intellectual disability.Case reportA Chinese pedigree with intellectual disability was collected in this study. Cytogenetic analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) followed by Sanger validation were conducted to identify the genetic pathogenesis. A novel heterozygous deletion c.370_374delTTCCC in TBR1 gene was identified, leading to a frameshift mutation starting at Phe124 followed by a premature stop codon at position 141 (p.Phe124Valfs118). Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. Prenatal diagnosis indicated the absence of this mutation, and the family decided to continue the pregnancy after genetic counseling.ConclusionOur findings demonstrated the significance of genetic testing in the diagnosis of intellectual disability. This work also confirmed the effectiveness of WES in prenatal diagnosis.     

Novel prenatally diagnosed compound heterozygous PXDN variants in fetal congenital primary aphakia and blepharophimosis

ObjectiveTo precision survey a fetal congenital primary aphakia molecular etiology.Case reportA case of 42 years old pregnancy woman prenatal diagnostic examination by amniocentesis conducted at 17 weeks' gestation and demonstrated a normal female karyotype. Trio studies based on chromosome microarray analysis (CMA) and Sanger's genetic analysis did not detect a pathologic variant of the FOXE3 gene. Fetal congenital primary aphakia accompanied with microphthalmia detected by sonography in the second trimester (22 weeks). MRI indicated bilateral absence of the lenses, consistent with primary congenital aphakia. Due to the poor prognosis of congenital aphakia, the parents decided to terminate the fetus and provided consent for an autopsy. Pathological analysis revealed dysplasia of the anterior segment of both eyes. However, post fetal mortem extended trio whole exon sequencing (WES) and Sanger's genetic analysis identified compound heterozygous variants in the chromosomal location 2p25.3 in the PXDN gene.ConclusionExtended whole exon sequencing is an important tool to study primary congenital aphakia.     

Mucopolysaccharidosis type VII as a cause of recurrent non-immune hydrops fetalis

BACKGROUND: Mucopolysaccharidosis type VII (MPS VII) is a rare lysosomal storage disease first described by Sly in 1973. There are fewer than thirty reported cases world wide. This extremely rare disorder can present in-utero as hydrops fetalis and has a high recurrence rate. However, prenatal diagnosis in the absence of a previously affected child, has not been reported to date. CASE: This is a case of a non-consanguineous couple, with no history of a previously affected child with MPS VII, presenting with recurrent hydrops fetalis. During the work-up, the affected fetus was diagnosed in-utero with beta-glucuronidase deficiency which is pathognomonic for MPS VII. Prenatal diagnosis was then performed in subsequent pregnancies. CONCLUSION: The importance of an extensive and thorough investigation for the etiology of hydrops fetalis is discussed.     

Successful treatment of extremely severe fetal anemia due to anti-Jra alloimmunization

BACKGROUND: Although Jr(a) hemolytic disease of the newborn (HDN) is generally considered to be mild, we encountered a case of anti-Jr(a) alloimmunization hydrops fetalis due to extremely severe fetal anemia that required aggressive intrauterine treatment. CASE REPORT: A Japanese woman developed hydrops fetalis at the 29th week of gestation. Blood examination was highly positive for anti-Jr(a) antibodies. Cordocentesis demonstrated that the fetus had anti-Jr(a) antibodies and the lowest fetal hemoglobin concentration was 2.3 g/dl. After a total of four intravascular transfusions, fetal hydrops improved and a healthy girl of 2,120 g was delivered at the 35th week of gestation. The initial neonatal hemoglobin concentration at birth was 7.2 g/dl. After two straight transfusions, the infant's anemia did not worsen. Anti-Jr(a) antibodies became negative without developing hyperbilirubinemia. CONCLUSION: The incidence of Jr(a) negativity can lead to underestimation of the risk of Jr(a) alloimmunization. This case shows that anti-Jr(a) alloimmunization may cause HDN and hydrops fetalis.     

A false-positive result at non-invasive prenatal testing due to maternal 17p12 microduplication

ObjectiveWe present a false-positive result at non-invasive prenatal testing (NIPT) due to maternal 17p12 microduplication.Case reportA 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) revealed the result of a 1.3-Mb duplication of 17p12 or arr [GRCh37] 17p12 (14,111,772–15,442,066) × 3 encompassing four Online Mendelian Inheritance in Man (OMIM) genes of COX10, HS3ST3B1, PMP22 and TEKT3. The mother did not have any neurologic problems. The parents were phenotypically normal. aCGH analysis of maternal blood revealed that the mother carried the same 17p12 microduplication. Two years ago, NIPT analysis during her first pregnancy revealed abnormality of chromosome 17 with 17p11.2p12 duplication. However, subsequent aCGH analysis at amniocentesis revealed no genomic imbalance in the fetus, and no further examination of the parental bloods was made. During this pregnancy, prenatal ultrasound was unremarkable, and the parents decided to continue the pregnancy.ConclusionA false-positive result at NIPT should raise a suspicion of maternal genomic imbalance.     

Prenatal diagnosis and molecular genetic analysis of short rib-polydactyly syndrome type III (Verma-Naumoff) in a second-trimester fetus with a homozygous splice site mutation in intron 4 in the NEK1 gene

ObjectiveTo demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type III short rib-polydactyly syndrome (SRPS) (Verma-Naumoff).Case ReportA 34-year-old woman with no past history of fetal SRPS was referred to the hospital at 21 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed a narrow thorax, short ribs, short limbs with marginal spurs, and postaxial hexadactyly in both the hands and feet. A diagnosis of SRPS III (Verma-Naumoff) was made. Amniocentesis was performed. The karyotype was 46,XY. Molecular genetic analysis of the amniotic fluid cells identified a homozygous splice site mutation in intron 4 (c.331-1 A > G) or IVS4-1 A > G in the NEK1 gene. The parents were heterozygous for the mutation. The pregnancy was subsequently terminated and a malformed fetus was delivered with prominent forehead, a flattened nasal bridge, a narrow and short trunk, a protuberant abdomen, bilateral postaxial polydactyly and syndactyly of the hands and feet, and micromelic limbs. No facial cleft or genital abnormality was noted. The radiograph was consistent with SRPS III.ConclusionPolydactyly, micromelia, metaphyseal spurs, widened humeral metaphyses, and shortened ribs can be prominent prenatal ultrasound findings of SRPS III. The present case provides evidence for a correlation of a mutation in the NEK1 gene with SRPS III.     

Simplified PGD of common determinants of haemoglobin Bart’s hydrops fetalis syndrome using multiplex-microsatellite PCR

The high incidence of double-gene deletions in α-thalassaemia increases the risk of having pregnancies with homozygous α⁰-thalassaemia, the cause of the lethal haemoglobin (Hb) Bart’s hydrops fetalis syndrome. Preimplantation genetic diagnosis (PGD) has played an important role in preventing such cases. However, the current gap-PCR based PGD protocol for deletional α-thalassaemia requires specific primer design for each specific deletion. A universal PGD assay applicable to all common deletional determinants of Hb Bart’s hydrops fetalis syndrome has been developed. Microsatellite markers 16PTEL05 and 16PTEL06 within the α-globin gene cluster were co-amplified with a third microsatellite marker outside the affected region in a multiplex-PCR reaction and analysed by capillary electrophoresis. Eight informed couples at risk of having Hb Bart’s hydrops fetalis were recruited in this study and all patients underwent standard procedures associated with IVF. A total of 47 embryos were analysed. Three pregnancies were achieved from three couples, with the births of two healthy babies and one ongoing pregnancy. This work has successfully adapted an earlier protocol and developed a simple and reliable single-cell assay applicable to PGD of Hb Bart’s hydrops fetalis syndrome regardless of type of deletion.Alpha-thalassaemia is one of the most common inheritable disorders worldwide. It is a blood disorder that, in its lethal form caused by deletion of all four copies of the α-globin gene, results in the demise of the affected fetus, a condition referred to as haemoglobin (Hb) Bart’s hydrops fetalis syndrome. Preimplantation genetic diagnosis (PGD) has played an important role in preventing such cases. Current PGD protocols for deletional α-thalassaemia utilize a strategy called gap-PCR, which requires the different assays for different deletion types. We have developed a universal PGD assay applicable to all common deletional determinants of Hb Bart’s hydrops fetalis syndrome based on microsatellite marker analysis. Eight informed couples at risk of having Hb Bart’s hydrops fetalis were recruited in this study and all patients underwent standard procedures associated with IVF. Forty-five embryos were analysed in total. Three pregnancies were achieved from three couples, with the births of two healthy babies and one pregnancy still ongoing. We have successfully adapted our earlier protocol and developed a simple and reliable single cell assay applicable to PGD of Hb Bart’s hydrops fetalis syndrome regardless of the type of deletion.     

Prenatal diagnosis of twin-twin transfusion syndrome complicated with hydrops fetalis at 14 weeks of gestation.

Twin-twin transfusion syndrome (TTTS) may complicate multiple pregnancy. Monochorionic discordant twins with oligohydramnios and polyhydramnios may be diagnostic. Hydrops fetalis is particularly ominous. All the signs can appear independently at any stage of gestation. However, TTTS with hydrops fetalis in early pregnancy is rare. We report here a case of TTTS complicated with hydrops fetalis diagnosed at 14 weeks of gestation. Our case may be one of the earliest cases of the prenatal diagnosis of TTTS complicated with hydrops fetalis in the literature.