ABSTRACT
OBJECTIVES: To analyse additional structural and genetic anomalies in fetuses with acrania/exencephaly/anencephaly sequence (AEAS). METHODS: A retrospective analysis of 139 fetuses with AEAS diagnosed between 2006 and 2020 in a single tertiary referral ultrasound department. RESULTS: The median gestational age at diagnosis decreased from 15 weeks in 2006 to 13 weeks in 2020 (- 0.21 per each year; p = 0.009). In 103 fetuses, the defects were limited to the neural tube (NTD) (74.1%), in 36 fetuses (25.9%), there were additional structural non-NTD anomalies. The most common were ventral body wall defects present in 17.8% (23/139), followed by anomalies of the limbs (7.2%; 10/139), face (6.5%; 9/139) and heart (6.5%; 9/139). Genetic anomalies were diagnosed in 7 of the 74 conclusive results (9.5%; 7/74; trisomy 18, n = 5; triploidy, n = 1; duplication of Xq, n = 1). In univariate logistic regression models, male sex, limb anomalies and ventral body wall defects significantly increased the risk of genetic anomalies (OR 12.3; p = 0.024; OR 16.5; p = 0.002 and OR 10.4; p = 0.009, respectively). CONCLUSIONS: A significant number of fetuses with AEAS have additional structural non-NTD anomalies, which are mostly consistent with limb body wall complex. Genetic abnormalities are diagnosed in almost 10% of affected fetuses and trisomy 18 is the most common aberration. Factors that significantly increased the odds of genetic anomalies in fetuses with AEAS comprise male sex, limb anomalies and ventral body wall defects.
Subject(s)
Anencephaly , Neural Tube Defects , Pregnancy , Female , Male , Humans , Infant , Anencephaly/diagnostic imaging , Anencephaly/epidemiology , Anencephaly/genetics , Trisomy 18 Syndrome , Retrospective Studies , Neural Tube Defects/diagnostic imaging , Neural Tube Defects/epidemiology , Prenatal DiagnosisABSTRACT
We present three new cases and review of the literature on the prenatal diagnosis of Emanuel syndrome (ES). Twenty-one foetuses have been analysed. In all three cases diagnosed in our department, posterior fossa abnormalities were seen and in one hypoplastic right ventricle was diagnosed at the first trimester scan. Defects of the posterior fossa (62% of foetuses; 13/21) and left diaphragmatic hernia (29% of foetuses; 6/21) are the most frequently reported prenatal findings in ES syndrome. No pattern of specific prenatal ultrasound markers of ES exists. Abnormalities of the posterior fossa are frequent and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing.IMPACT STATEMENTWhat is already known on this subject? Emanuel syndrome (ES) is a rare genetic disorder. No pattern of specific prenatal ultrasound markers exists. The great majority of cases is diagnosed postnatally and only a few cases of prenatal diagnosis have been published to date.What do the results of this study add? The most frequent structural abnormalities in prenatally detected ES involved central nervous system (80.9%), namely posterior fossa defects (57.1%) and mild ventriculomegaly (23.8%). Other frequent abnormalities include left diaphragmatic hernia (28.6%), renal defects (23.8%) and foetal growth restriction (FGR) (23.8%).What are the implications of these findings for clinical practice and/or further research? Abnormalities of the posterior fossa are the most frequent defects in ES and may be diagnosed as early as in the first trimester of pregnancy. Specific diagnosis can be made only after invasive genetic testing.
Subject(s)
Chromosome Disorders , Hernia, Diaphragmatic , Female , Pregnancy , Humans , Ultrasonography, Prenatal/methods , Prenatal DiagnosisABSTRACT
BACKGROUND: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. METHODS: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. RESULTS: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. CONCLUSIONS: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.
Subject(s)
Exome , Genetic Counseling , Exome/genetics , Female , Humans , Poland , Pregnancy , Prenatal Diagnosis/methods , Exome Sequencing/methodsABSTRACT
PURPOSE: To establish the distribution of diandric and digynic triploidy depending on gestational age. METHODS: 107 triploid samples tested prospectively in a single genetic department during a four-year period were analyzed for parental origin of triploidy by Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) (n=95) with the use of matching parental samples or by MS-MLPA (n=12), when parental samples were unavailable. Tested pregnancies were divided into three subgroups with regard to the gestational age at spontaneous pregnancy loss: <11 gestational weeks, 11-14 gestational weeks, and >14 gestational weeks. RESULTS: Diandric triploidy constituted overall 44.9% (46.5% in samples miscarried <11 gestational weeks, 64.3% in samples miscarried between 11 and 14 gestational weeks, and 27.8% in pregnancies which survived >14 gestational weeks). CONCLUSIONS: The distribution of diandric and digynic triploidy depends on gestational age. The majority of diandric triploid pregnancies is lost in the first trimester of pregnancy. In the second trimester, diandric cases are at least twice less frequent than digynic ones.
Subject(s)
Abortion, Spontaneous/epidemiology , Gestational Age , Pregnancy Trimester, First , Pregnancy Trimester, Second , Triploidy , Abortion, Spontaneous/genetics , Female , Humans , Male , Poland/epidemiology , Pregnancy , Prospective StudiesABSTRACT
Triploidy is a life-limiting genetic aberration resulting from an extra haploid set of chromosomes of paternal (diandric triploidy) or maternal origin (digynic triploidy). Triploidy affects around 1%-2% of all conceptions. The majority of cases is miscarried at early developmental stages. In consequence of genomic imprinting, parental origin affects the phenotype of triploid pregnancies as well as the prevalence and spectrum of related maternal complications. Distinctive ultrasound features of both triploid phenotypes as well as characteristic patterns of biochemical markers may be useful in diagnosis. Molecular confirmation of the parental origin allows to predict the risk of complications, such as gestational trophoblastic neoplasia, hyperthyroidism, hypertension, or preeclampsia associated with the paternal origin of triploidy. Diagnosis of partial hydatidiform mole associated with diandric triploidy is challenging especially in the first trimester pregnancy loss due to the limitations of both histopathology and ultrasound. We present important clinical aspects of triploid pregnancies and indicate unresolved issues demanding further studies.
Subject(s)
Abortion, Spontaneous/genetics , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Triploidy , Chromosome Disorders/epidemiology , Female , Fetal Growth Retardation/genetics , Genetic Testing , Genomic Imprinting , Humans , Hydatidiform Mole/diagnosis , Hydatidiform Mole/genetics , Phenotype , Pregnancy , Prenatal Diagnosis , Prevalence , Recurrence , Ultrasonography, PrenatalABSTRACT
INTRODUCTION: Inborn errors of metabolism (IEM) also called metabolic diseases constitute a large and heterogenous group of disorders characterized by a failure of essential cellular functions. Antenatal manifestation of IEM is absent or nonspecific, which makes prenatal diagnosis challenging. Glutaric acidemia type 2 (GA2) is a rare metabolic disease clinically manifested in three different ways: neonatal-onset with congenital anomalies, neonatal-onset without congenital anomalies and late-onset. Neonatal forms are usually lethal. Congenital anomalies present on prenatal ultrasound as large, hyperechoic or cystic kidneys with reduced amniotic fluid volume. MATERIAL AND METHODS: We present a systematic literature review describing prenatal diagnosis of GA2 and a new prenatal case. RESULTS: Ten prenatally diagnosed cases of GA2 have been published to date, mainly based on biochemical methods. New case of GA2 was diagnosed using exome sequencing method. DISCUSSION: All prenatal cases from literature review had positive history of GA2 running in the family. In our study trio exome sequencing was performed in case of fetal hyperechoic kidneys without a history of GA2. Consequently, we were able to identify two novel pathogenic variants of the ETFDH gene and to indicate their parental origin. SUMMARY: Exome sequencing approach used in case of fetal hyperechoic kidneys allows to identify pathogenic variants without earlier knowledge of the precise genetic background of the disease. Hyperechoic, enlarged kidneys could be one of the clinical features of metabolic diseases. After exclusion of chromosomal abnormalities, urinary tract obstruction and intrauterine infections, glutaric acidemia type 2 and number of monogenic disorders should be consider.
Subject(s)
Metabolism, Inborn Errors/genetics , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/diagnosis , Prenatal Diagnosis/methods , Adult , Exome , Female , Humans , Infant, Newborn , Metabolic Diseases , Metabolism, Inborn Errors/diagnosis , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/genetics , Pregnancy , Exome SequencingABSTRACT
OBJECTIVE: To analyse natural course and perinatal management in twin pregnancies discordant for digynic triploidy. CASE REPORT: We present five cases of twins discordant for digynic triploidy. Pregnancy outcome was known for three of them. In one case, premature rupture of membranes occurred at 20 gestational weeks and both fetuses were miscarried. In two other pregnancies healthy co-twins were born at term after the triploid fetuses demise at 28 and 37 weeks. No maternal complications were observed. CONCLUSION: Twin pregnancies discordant for triploidy poses a challenge for perinatal management. Expectant management should be considered in digynic triploid cases.
Subject(s)
Diseases in Twins/genetics , Pregnancy, Twin , Triploidy , Adult , Diseases in Twins/diagnosis , Diseases in Twins/embryology , Female , Humans , Pregnancy , Pregnancy Outcome , Prenatal Diagnosis , Watchful WaitingABSTRACT
Triploidy is a genetic aberration resulting from an extra haploid set of chromosomes of paternal (diandric) or maternal (digynic) origin. Diandric cases, opposite to digynic ones, may lead to gestational trophoblastic neoplasia (GTN) or generate maternal complications, therefore their identification is crucial, but reproducibility of traditionally used histopathological assessment is poor. The aim of the study was to analyse the usefulness of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) with probes for two differentially methylated regions (DMR) at chromosome 11p.15.5 for identification of the parental origin of triploidy. 84 triploid DNA samples were tested with MS-MLPA: 34 paternal cases (40.5%) and 50 maternal ones (59.5%) according to the reference results of QF-PCR. Methylation ratio (MR) was calculated. Reference values proposed by the MRC-Holland for diploid samples (MR 0.8-1.2) were used. The values outside these ranges were used to diagnose parental origin of triploidy-paternal (MR > 1.2) or maternal (MR < 0.8). The effectiveness of MS-MLPA was 94.0%. The mean MR in paternal triploidy was 1.7 (SD-0.25; n = 34) compared with 0.56 in maternal triploidy (SD-0.12; n = 50). MR values in paternal and maternal triploidy did not overlap. In five samples (6.0%) parental origin of triploidy could not be accurately established by MS-MLPA, probably due to the maternal cell contamination (MCC). MS-MLPA can be used as a convenient method for distinguishing between paternal and maternal triploidy without the necessity for parental samples testing. It enables adequate selection of the paternal triploid cases for follow up in order to exclude post-molar GTN.
Subject(s)
Chromosomes, Human, Pair 11/genetics , DNA Methylation , Genomic Imprinting , Klinefelter Syndrome/genetics , Multiplex Polymerase Chain Reaction , Sex Chromosome Disorders of Sex Development/genetics , Sex Chromosome Disorders/genetics , Triploidy , Trisomy/genetics , XYY Karyotype/genetics , Abortion, Spontaneous/genetics , Amniocentesis , Chorionic Villi Sampling , Chromosomes, Human, X/genetics , Female , Gestational Age , Humans , Male , Pregnancy , Sex Chromosome AberrationsABSTRACT
PURPOSE: To evaluate the trends in prenatal diagnosis over 26 years in a tertiary referral hospital. METHODS: A retrospective analysis of invasive prenatal procedures performed between 1991 and 2016. Maternal characteristics, indications for invasive diagnosis, and percentage of abnormal karyotypes were compared between periods according to guidelines implemented nationally and locally. RESULTS: A total of 14,302 invasive prenatal procedures were performed. The proportion of invasive procedures performed for advanced maternal age, abnormal karyotype in a previous pregnancy, and maternal anxiety decreased from 71.1%, 17.8%, 8.9% in 1991 to 23.9%, 1.3%, and 2.3% in 2016 (OR 0.6, 0.8, and 0.9 for each 5 years, respectively; p < 0.001), while the proportion of invasive procedures performed for abnormal ultrasound increased from 2.2% in 1991 to 51.6% in 2016 (OR 1.9 for each 5 years; p < 0.001). Abnormal karyotype was found in 9.7%. The proportion of abnormal karyotypes increased significantly from 0.0% in 1991 to 15.7% in 2016 (OR 1.35 for each 5-year period; p < 0.001). The odds of abnormal karyotype increased after the implementation of the Ordinance of the Minister of Health in 2003 (OR 1.6), the National Prenatal Screening Program in 2007 (OR 2.2), and the in-house genetic counseling with combined first trimester screening in 2015 (OR 3.1). CONCLUSIONS: Significant changes in prenatal diagnosis led to a better selection of patients undergoing invasive prenatal procedures. The implementation of in-house genetic counseling was associated with an increased rate of the detection of abnormal karyotypes.
Subject(s)
Abnormal Karyotype , Genetic Counseling , Karyotyping , Prenatal Diagnosis , Adult , Aneuploidy , Child, Preschool , Female , Humans , Karyotyping/standards , Maternal Age , Poland/epidemiology , Pregnancy , Pregnancy Trimester, First , Tertiary Care CentersABSTRACT
OBJECTIVES: To determine the frequency of genetic and additional structural abnormalities as well as pregnancy outcomes in fetuses with prenatally diagnosed cephalocele. METHODS: A retrospective analysis of data retrieved from ultrasound examinations and genetic testing in fetuses with cephalocele diagnosed between 2006 and 2018 in a tertiary referral hospital along with a systematic literature search in the PubMed database on fetuses with prenatally diagnosed cephalocele. RESULTS: Twenty-one out of 36 fetuses were found to have additional structural anomalies (58.3%). In four fetuses, anomalies were consistent with limb-body wall complex, in five with Meckel-Gruber syndrome, and in one with amniotic band syndrome. Genetic abnormalities were present in 11.1% of fetuses (trisomy 6; microdeletion 22q11.21; microduplication 16p13.11; pathogenic variant in gene CC2D2A). Twenty-eight pregnancies were terminated (77.8%; 28/36); two were miscarried (5.6%; 2/36). All six children from pregnancies that continued were liveborn but only two survived the surgery and developed neurological sequence. Overall survival rate was 25% (2/8) with 0% intact survival. CONCLUSIONS: Additional structural anomalies are common in fetuses with cephalocele. A significant number of fetuses have genetic abnormalities, and a detailed genetic testing should be performed in all cases. The prognosis is poor with high mortality rate and 0% intact survival.
Subject(s)
Abnormalities, Multiple/diagnosis , Amniotic Band Syndrome/diagnosis , Ciliary Motility Disorders/diagnosis , Encephalocele/diagnostic imaging , Polycystic Kidney Diseases/diagnosis , Retinitis Pigmentosa/diagnosis , Trisomy/diagnosis , Abnormalities, Multiple/genetics , Abortion, Induced , Abortion, Spontaneous , Amniotic Band Syndrome/genetics , Chromosome Deletion , Chromosome Duplication , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 6 , Ciliary Motility Disorders/genetics , Cohort Studies , Cytoskeletal Proteins/genetics , Encephalocele/diagnosis , Encephalocele/genetics , Female , Humans , Infant, Newborn , Male , Perinatal Death , Polycystic Kidney Diseases/genetics , Pregnancy , Retinitis Pigmentosa/genetics , Retrospective Studies , Trisomy/genetics , Ultrasonography, PrenatalABSTRACT
Otocephaly is an extremely rare lethal congenital anomaly characterized by the absence or underdevelopment of the mandible. The clinical presentation is variable. Some cases may present with severe micrognathia as the only anomaly seen prenatally. The key to early diagnosis is careful assessment of the location of the fetal ears on 2D ultrasound examination.
Subject(s)
Craniofacial Abnormalities/diagnostic imaging , Craniofacial Abnormalities/embryology , Ear/diagnostic imaging , Ear/embryology , Ultrasonography, Prenatal/methods , Abortion, Eugenic , Adult , Female , Humans , PregnancyABSTRACT
OBJECTIVE: The objective of the study is to analyse the sonographic features, cytogenetic results and pregnancy outcomes in complex malformations involving the body wall in a large cohort of fetuses with regard to different definitions proposed in the literature. METHOD: A retrospective study on 96 fetuses with complex malformations comprising ventral wall, craniofacial structures, limbs and umbilical cord that were evaluated between 1997 and 2015. RESULTS: The most common sonographic finding was an extensive ventral wall defect (95.8%; 92/96) comprising liver (94.6%; 87/92), intestine (82.6%; 76/92), heart (17.4%; 16/92) and bladder (8.7%; 8/92). Acrania and encephalocoele were observed in 24 and 9 fetuses (25.0%, 24/96; 9.4%, 9/96), respectively. Limb anomalies were present in 54 fetuses (56.3%; 54/96). Rudimentary or absent umbilical cord was observed in 62 fetuses (64.6%; 62/96). In 79 fetuses, there were additional multiple structural anomalies detected prenatally. None of the currently used definitions encompasses all possible phenotypes of body wall defects present in our cohort. Chromosomal aberrations were seen in 8 out of 60 cases with conclusive cytogenetic result (13.3%, 8/60). CONCLUSION: Chromosomal anomalies are common, and karyotyping should be offered. There is a need for a more rigorous classification of complex malformations in order to better understand the underlying pathophysiology. © 2017 John Wiley & Sons, Ltd.
Subject(s)
Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/embryology , Ultrasonography, Prenatal , Chromosome Aberrations/embryology , Encephalocele/diagnostic imaging , Encephalocele/embryology , Female , Gestational Age , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/embryology , Humans , Intestines/abnormalities , Intestines/diagnostic imaging , Intestines/embryology , Limb Deformities, Congenital/diagnostic imaging , Limb Deformities, Congenital/embryology , Liver/abnormalities , Liver/diagnostic imaging , Liver/embryology , Neural Tube Defects/diagnostic imaging , Neural Tube Defects/embryology , Pregnancy , Pregnancy Outcome , Retrospective Studies , Umbilical Cord/abnormalities , Umbilical Cord/diagnostic imaging , Urinary Bladder/abnormalities , Urinary Bladder/embryologyABSTRACT
OBJECTIVES: To analyze sonographic abnormalities in triploid pregnancies and assess the usefulness of the classification proposed by McFadden and Kalousek for prenatal sonographic assessment of triploid fetuses. METHODS: We conducted a retrospective analysis of the sonographic features in a series of 67 triploid fetuses evaluated between 11 and 30 weeks of gestation in a single referral center between 1997 and 2015. RESULTS: Non-specific structural fetal defects were visualized in the majority of fetuses (61.2%) regardless of the parental origin of the triploidy. A 'diandric phenotype' was identified in eight relatively well-grown fetuses (11.9%) that presented with cystic placentas. A 'digynic phenotype' was identified in 47 asymmetrically growth-restricted fetuses with non-cystic placentas (70.2%). In 12 cases (17.9%), features of both phenotypes were present. CONCLUSIONS: Nearly 40% of triploid fetuses do not have any apparent structural abnormalities, and only careful assessment of fetal growth and placenta may lead to the suspicion of the diagnosis. As diandric triploidy carry a high risk for maternal complications, identification of these cases is vital for prenatal counseling. In nearly 20% of triploid pregnancies, parental origin cannot be established based on sonographic assessment. © 2017 John Wiley & Sons, Ltd.
Subject(s)
Triploidy , Ultrasonography, Prenatal , Adult , Female , Humans , Phenotype , Pregnancy , Retrospective Studies , Young AdultABSTRACT
AIM: The aim of this study was to analyze the influence of effective preconceptional testing for carrier status in women at risk for Duchenne and Becker muscular dystrophies (D/BMD) on the prenatal diagnosis. METHODS: A retrospective analysis of 201 prenatal tests was performed in 169 Polish women at risk, in regard to time of testing for carrier status (prior to conception or during pregnancy) and carrier status of tested women, including confirmed D/BMD carriers (n = 78; 46.2%), D/BMD non-carriers - tested for germline mosaicism risk (n = 23; 13.6%), and women at risk with uncertain carrier status (n = 68; 40.2%). RESULTS: Only 52.7% of women were tested for D/BMD carrier status prior to conception and in these women prenatal diagnosis was carried out more frequently in the first trimester of pregnancy (64.7% vs 47.8%; P = 0.035). The results of prenatal testing in male fetuses in pregnancies of confirmed D/BMD carriers and D/BMD non-carriers - tested for germline mosaicism risk were conclusive in all cases, whereas in women with uncertain carrier status, only 60.0% of results were conclusive. Eighty-five of 103 female fetuses (82.5%) were tested prenatally and in 31.8% of them fetal carrier status was confirmed. CONCLUSION: Carrier status testing in women prior to conception has a positive impact on the frequency of first-trimester prenatal diagnosis and known D/BMD carrier status on the effectiveness of prenatal diagnosis. Due to the low percentage of women tested effectively prior to conception, carrier status testing in the families at risk should be propagated (including possibility of prenatal diagnosis of female fetuses).
Subject(s)
Amniocentesis/statistics & numerical data , Chorionic Villi Sampling/statistics & numerical data , Cordocentesis/statistics & numerical data , Heterozygote , Muscular Dystrophy, Duchenne/diagnosis , Secondary Prevention , Adult , Female , Humans , Male , Pregnancy , Pregnancy Trimester, First , Retrospective StudiesSubject(s)
Anemia , Blood Transfusion/methods , Cesarean Section/methods , Dystocia , Fetomaternal Transfusion , Infant, Newborn, Diseases , Adult , Anemia/diagnosis , Anemia/etiology , Anemia/therapy , Cardiotocography/methods , Dystocia/diagnosis , Dystocia/surgery , Emergency Treatment/methods , Female , Fetomaternal Transfusion/diagnosis , Fetomaternal Transfusion/physiopathology , Fetomaternal Transfusion/surgery , Flow Cytometry/methods , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/etiology , Infant, Newborn, Diseases/therapy , Male , Pregnancy , Severity of Illness Index , Treatment OutcomeABSTRACT
OBJECTIVE: To present five new cases of prenatally diagnosed Pallister-Killian syndrome (PKS) and to propose an approach for a targeted diagnosis. METHOD: We retrospectively analyzed ultrasound findings and cytogenetic results in PKS. We also searched through dysmorphology databases for features occurring in PKS that could potentially be seen in prenatal ultrasound examination. RESULTS: On the basis of collected data, frequent and distinctive features in fetuses with PKS were established. The most appropriate material and method of testing were proposed. Rhizomelic limb shortening, diaphragmatic hernia, thickened nuchal fold, increased prenasal thickness, polydactyly and polyhydramnios were frequent and distinctive findings in fetuses with PKS. Amniocentesis was the most frequent prenatal procedure for material collection. Percentage of aneuploid cells was higher in amniotic fluid than in cord blood. Cytomolecular tests were useful as confirmation as well as preliminary tests. Cytogenetic identification of the isochromosome was done in all cases except one. CONCLUSIONS: In case of ultrasound evaluation of features frequent and distinctive for PKS in second and third trimesters of pregnancy, targeted diagnosis should be considered. Amniotic fluid instead of cord blood collection is preferable. Communication with the laboratory is important because modification of routine procedures enhances a chance for correct diagnosis. © 2017 John Wiley & Sons, Ltd.
Subject(s)
Chromosome Disorders/diagnosis , Prenatal Diagnosis/methods , Abortion, Eugenic , Adult , Chromosomes, Human, Pair 12 , Cytogenetic Analysis , Female , Gestational Age , Humans , Maternal Age , Pregnancy , Pregnancy Outcome , Retrospective Studies , Ultrasonography, Prenatal , Young AdultABSTRACT
Around 10-15% of pregnancies result in a spontaneous first trimester miscarriage, which is most frequently caused by chromosomal abnormalities, mainly aneuploidies. Genetic analysis of pregnancy loss includes conventional G-banding karyotyping and various molecular methods. Apart from variable methodological limitations, the effectiveness of genetic analysis depends on the type and quality of the tested sample. To improve the reliability of genetic testing, we present methods of appropriate collection and pre-laboratory preparation of chorionic villi from first trimester miscarriage. We also discuss issues of maternal cell contamination, placental mosaicism and reciprocal and Robertsonian translocations in the context of interpretation of the results and genetic counseling.
Subject(s)
Abortion, Spontaneous/genetics , Chromosome Disorders/diagnosis , Genetic Testing/methods , Pregnancy Trimester, First/genetics , Chorionic Villi Sampling , DNA Probes , Female , Humans , Karyotyping/methods , PregnancyABSTRACT
OBJECTIVE: The objective of this study is to determine the risk of aneuploidy, associated structural anomalies, and pregnancy outcome in the presence of prenatal double bubble sign detection. METHOD: We have performed a retrospective study on ultrasound reports and pregnancy outcomes in 42 fetuses with double bubble sign examined in our ultrasound department between 1998 and 2013. RESULTS: Additional major defects or aneuploidy markers were present in 24 fetuses. Chromosomal abnormalities occurred in 21 cases. There were 35 live births; two pregnancies ended in intrauterine fetal demise; five patients opted for termination of pregnancy because of additional anomalies or abnormal karyotype. Postnatal or postmortem verification revealed duodenal obstruction secondary to intrinsic or extrinsic cause in 40 cases; in one case, proximal jejunal atresia was diagnosed, and one neonate had normal bowel. CONCLUSIONS: Sonographic double bubble sign is associated with a significant rate of major anatomic defects, abnormal karyotype, and unfavorable pregnancy outcome. It is strongly indicative of duodenal obstruction.
Subject(s)
Aneuploidy , Congenital Abnormalities/diagnostic imaging , Duodenal Obstruction/diagnostic imaging , Adult , Chromosome Aberrations , Congenital Abnormalities/epidemiology , Duodenal Obstruction/epidemiology , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiology , Retrospective Studies , Ultrasonography, Prenatal , Young AdultABSTRACT
OBJECTIVES: Presentation of our own, preliminary experiences in the assessment of the right subclavian artery's (RSA) position during the second trimester scan. MATERIAL AND METHODS: Since January 2012 our center has started to conduct the assessment of the position of the right subclavian artery in the second trimester scan. Patients who were diagnosed with an aberrant right subclavian artery (ARSA) were referred to invasive method of prenatal diagnosis. Abnormal karyotype and microdeletion 22q11 were analyzed. Detailed echocardiography was conducted in each case. RESULTS: Between January 2012 and September 2013 we diagnosed 19 cases of ARSA. There were three cases of congenital heart defect (15.8%; 3/19) (ventricular septal defect--VSD, n=2, atrioventricular septal defect--AVSD, n=1). Two out of 17 cases showed an abnormal karyotype (11.8%; 2/17)--46,XY del(5) (q15q31) and 47,XX+18. No 22q11.2 deletions were observed. Two patients did not consent to invasive methods of prenatal diagnosis. CONCLUSIONS: The position of the right subclavian artery (RSA) should be routinely assessed during the second trimester of ultrasound screening. The presence of ARSA increases the risk for abnormal karyotype in the fetus and therefore, all patients who are diagnosed with ARSA should be referred to the reference center.