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Annals of Pediatric Endocrinology &... Feb 2024Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was...
PURPOSE
Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk.
METHODS
This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively.
RESULTS
A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD.
CONCLUSION
This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.
PubMed: 38461806
DOI: 10.6065/apem.2346014.007 -
Medicine Mar 2024Because of the normal phenotype, carriers of specific chromosomal translocations are often diagnosed only after their development of associated malignancies, recurrent...
RATIONALE
Because of the normal phenotype, carriers of specific chromosomal translocations are often diagnosed only after their development of associated malignancies, recurrent miscarriages, and reproductive difficulties. In this paper, we report primary balanced fetal chromosomal translocations by performing the necessary invasive prenatal diagnosis in couples with previous malformations coupled with prenatal testing suggesting a high risk for trisomy 21.
PATIENT CONCERNS
Case 1 and Case 2 couples had malformed children, and Case 3 couples had a high risk of trisomy 21 on noninvasive preconception serological testing.
DIAGNOSIS AND INTERVENTION
A balanced chromosomal translocation diagnosis was confirmed by karyotyping of fetal cells obtained by amniocentesis.
OUTCOMES
All 3 couples decided to continue their pregnancies after learning about the consequences of the chromosomal abnormalities. Approximately a year after the children were born, the staff of the Prenatal Diagnostic Center followed up with a phone call and found that the children physical development and intelligence were normal.
LESSON
This case report reports healthy chromosomal balanced translocation newborns born to couples with poor maternal history and couples with abnormalities suggested by preconception testing, and followed up with the newborns to provide some experience in prenatal diagnosis and genetic counseling for chromosomal balanced translocations.
Topics: Pregnancy; Female; Child; Infant, Newborn; Humans; Translocation, Genetic; Down Syndrome; Chromosome Aberrations; Chromosome Disorders; Prenatal Diagnosis; Fetus; Abnormalities, Multiple; Chromosomes
PubMed: 38457559
DOI: 10.1097/MD.0000000000037345 -
Congenital Anomalies May 2024The phenotype of SCA patients are diversities, make prenatal counseling and parental decision-making following the prenatal diagnosis of SCA more complicated and...
Prenatal diagnosis, pregnancy determination and follow up of sex chromosome aneuploidy screened by non-invasive prenatal testing from 122 453 unselected singleton pregnancies: A retrospective analysis of 7-year experience.
The phenotype of SCA patients are diversities, make prenatal counseling and parental decision-making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Aneuploidy; Adult; Sex Chromosome Aberrations; Prenatal Diagnosis; Noninvasive Prenatal Testing; Follow-Up Studies; Amniocentesis
PubMed: 38454888
DOI: 10.1111/cga.12558 -
BMJ Case Reports Mar 2024A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed...
A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed a large-for-gestational-age foetus with a large abdominal circumference and liver, ventricular septal defect, right prominent renal pelvis and echogenic bowel. Antenatal genetic tests for overgrowth syndromes were negative. The mother had early onset pre-eclampsia. After birth, an overgrowth syndrome was still suspected despite the baby having normal birth parameters. Raw data of the trio whole exome sequencing from the amniocentesis sample were manually inspected. Hemizygous exon 7 deletion in the GPC3 gene was found, and a postnatal diagnosis of Simpson-Golabi-Behmel syndrome, a rare overgrowth syndrome, was made. This case report discusses the significance of antenatal findings, an atypical presentation of a rare syndrome and the obstacles of diagnostic genetic testing.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Arrhythmias, Cardiac; Genetic Diseases, X-Linked; Gigantism; Glypicans; Heart Defects, Congenital; Intellectual Disability
PubMed: 38442972
DOI: 10.1136/bcr-2021-247864 -
Case Reports in Women's Health Mar 2024Whole-exome sequencing is an evolving technology in perinatal diagnosis which allows identification of genetic etiologies that would otherwise go undetermined. In this...
Whole-exome sequencing is an evolving technology in perinatal diagnosis which allows identification of genetic etiologies that would otherwise go undetermined. In this case report, a 38-year-old Hispanic woman, G5P3013, with a monochorionic diamniotic twin gestation with one fetus displaying significant cranial abnormalities on prenatal ultrasound and magnetic resonance imaging (MRI) of the brain is presented. Fetal anomalies included bilateral ventriculomegaly, absent cavum septum pellucidum, and absent corpus callosum. Diagnostic amniocentesis with chromosome analysis, chromosomal microarray, alpha-fetoprotein, cytomegalovirus, toxoplasmosis, and parvovirus had normal results. Whole-exome sequencing for the anomalous fetus detected a de novo mosaic variant of uncertain significance (VUS) in the calcium/calmodulin dependent serine protein kinase () gene: . This variant was absent in the normal twin fetus, the mother, and the father. Pathogenic CASK gene mutations are associated with three syndromes: FG syndrome 4, intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH), and intellectual developmental disorder with or without nystagmus. Whole-exome sequencing identified a potential etiology for the anomalies detected. The variant likely arose de novo and was the potential cause of the identified cranial abnormalities in one fetus of this monochorionic diamniotic twin gestation. Whole-exome sequencing may provide additional diagnostic utility when standard diagnostic testing is noncontributory.
PubMed: 38440102
DOI: 10.1016/j.crwh.2024.e00583 -
Revista Colombiana de Obstetricia Y... Dec 2023To describe a case of prenatal diagnosis of Freeman-Sheldon syndrome based on ultrasound findings and complete fetal exome sequencing.
OBJECTIVES
To describe a case of prenatal diagnosis of Freeman-Sheldon syndrome based on ultrasound findings and complete fetal exome sequencing.
MATERIALS AND METHODS
A 33-year-old patient currently on treatment for hypothyroidism in whom a 19-week detailed anatomical ultrasound scan showed fetal deformities in more than two body areas (upper and lower limbs), suggesting a diagnosis of arthrogryposis. Genetic counseling was provided and amniocentesis was performed at 20 weeks for fluorescence in situ hybridization (FISH) analysis and complete fetal exome sequencing, with the latter allowing the identification of a heterozygous pathogenic variant of the MYH3 gene which is associated with type 2A distal arthrogryposis.
CONCLUSIONS
Complete fetal exome sequencing was a key factor in identifying the MYH3 gene mutation and confirmed that the deformities seen on ultrasound were associated with type 2A distal arthrogryposis. It is important to perform complete fetal exome sequencing in cases of joint malformations seen on prenatal ultrasound.
PubMed: 38421226
DOI: 10.18597/rcog.4019 -
The Journal of Maternal-fetal &... Dec 2024The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with species.
OBJECTIVES
The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with species.
METHODS
This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22-33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, , and spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement.
RESULTS
Intra-amniotic infection with spp. was diagnosed in 37 patients, intra-amniotic infection without spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55-71.2), but not in those with intra-amniotic infection without spp. or intra-amniotic inflammation without MIAC.
CONCLUSION
BPD was only associated with intra-amniotic infection with species.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Ureaplasma; Chorioamnionitis; Retrospective Studies; Bronchopulmonary Dysplasia; Prevalence; Interleukin-6; Prenatal Exposure Delayed Effects; Placenta; Premature Birth; Fetal Membranes, Premature Rupture; Amniotic Fluid; Inflammation
PubMed: 38418200
DOI: 10.1080/14767058.2024.2320670 -
Prenatal Diagnosis Mar 2024To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood.
OBJECTIVE
To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood.
METHODS
Blood was obtained from 401 (243 + 158) individuals (8-22 weeks) and shipped overnight. Red cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 and enriched for positive CK staining. Automated scanning was used to identify and pick single CK /CD45 trophoblasts which were subjected to next-generation sequencing.
RESULTS
Blood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin with Williams syndrome deletion). The deletion was confirmed in both fetuses. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results in 133 cases. Seven had aneuploidy results, and there were three likely pathogenic deletions/duplications, including one15q11-q13 deletion.
CONCLUSION
Although the sample size is modest and statistically accurate measures of test performance are not possible, the Luna test detected aneuploidy and deletions/duplications based on concordance with CVS/amniocentesis.
Topics: Pregnancy; Humans; Female; Placenta; Prenatal Diagnosis; Amniocentesis; Aneuploidy; Mosaicism; Genetic Testing
PubMed: 38411249
DOI: 10.1002/pd.6529 -
JNMA; Journal of the Nepal Medical... Feb 2024Dandy-Walker syndrome is a rare congenital central nervous system malformation. Dandy-Walker variant is characterised by cerebellar vermian hypoplasia, cystic fourth...
UNLABELLED
Dandy-Walker syndrome is a rare congenital central nervous system malformation. Dandy-Walker variant is characterised by cerebellar vermian hypoplasia, cystic fourth ventricular dilatation, and normal posterior fossa volume. Various prenatal tests such as ultrasound, fetal magnetic resonance imaging, and amniocentesis can help diagnose Dandy-Walker syndrome. Here, we report a case of the Dandy-Walker variant with meningitis in a neonate admitted to the neonatal intensive care unit due to multiple petechiae on the anterior abdominal wall, accompanied by peripheral cyanosis at the time of birth. Although maximum cases are diagnosed prenatally, some cases might be missed due to inadequate antenatal examination. Magnetic imaging resonance of the brain is best for the diagnosis of Dandy-Walker syndrome postnatally.
KEYWORDS
case reports; Dandy-Walker malformation, magnetic resonance imaging, meningitis.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Dandy-Walker Syndrome; Brain; Magnetic Resonance Imaging; Meningitis
PubMed: 38409968
DOI: 10.31729/jnma.8472 -
Nigerian Journal of Clinical Practice Feb 2024Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal...
BACKGROUND
Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal diagnostic measures are undertaken to prevent births with thalassemia major, a locally widespread genetic disease.
AIM
This study aims to evaluate the results of prenatal invasive diagnostic tests performed in a private obstetrics clinic in Northern Cyprus and show the diagnosis process of thalassemia and chromosomal anomalies.
MATERIALS AND METHODS
This study is a retrospective, descriptive study. Chorionic villus sampling (CVS) results and the amniocentesis tests performed between 1990 and 2022 are evaluated. Thalassemia and chromosome analysis of samples obtained by CVS and amniocentesis tests were performed. To diagnose alpha or beta thalassemia and sickle cell, 239 CVS was performed. And to diagnose chromosomal anomalies, 396 CVS and amniocentesis were performed.
RESULTS
The mean age of the 480 pregnant women included in the study was 31.12 years (18-46) and 30% of them were older than 34 years. The most common indications for invasive prenatal diagnostic test (IPDT) were; mother/father thalassemia minor/major, advanced maternal age, high risk of ultrasonography erase findings, and the noninvasive screening test. The result of IPDT detected 7.3% chromosomal anomaly and 69.5% thalassemia and sickle cell anemia. Of the 239 CVS performed to diagnose alpha or beta thalasemia and sickle cell, 23.4% beta major, 42.3% beta minor, and 2.1% alpha minor were diagnosed. Of the 396 CVS and amniocentesis performed to diagnose chromosomal anormalies; 2.8% of Down syndrome and 4.54% of other chromosomal anomalies were diagnosed.
CONCLUSION
IPDT is important in correctly diagnosing fetal anomalies at the prenatal stage to help families decide at the right time.
Topics: Pregnancy; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Retrospective Studies; Cyprus; Prenatal Diagnosis; Chorionic Villi Sampling; Chromosome Aberrations; Chromosome Disorders; Thalassemia; Anemia, Sickle Cell; Diagnostic Tests, Routine
PubMed: 38409146
DOI: 10.4103/njcp.njcp_540_23