Extended genetic testing in fetuses with sonographic skeletal system abnormalities.

OBJECTIVES: To analyze genetic causes of skeletal system abnormalities diagnosed by prenatal sonography and to establish a diagnostic protocol with regard to extended genetic testing in this group of patients. METHODS: This prospective observational cohort study included all singleton pregnancies with a sonographic abnormality of the skeletal system evaluated in a single ultrasound department during a 1-year period (2019). Fetuses underwent routine genetic testing by chromosomal microarray analysis (CMA) supplemented with polyploidy testing, and those with either a normal result or an abnormal result not consistent with the observed phenotype underwent exome sequencing (ES). Interpretation of variants was discussed by a panel of specialists to identify pathogenic/likely pathogenic variants. RESULTS: The study group comprised 55 fetuses. A chromosomal abnormality consistent with the observed phenotype was detected in 24 (43.6%) cases. After exclusions, 26 (47.3%) cases underwent further molecular testing by ES, of which 18 (69.2%) were classified as having abnormal ES results, thus increasing the diagnostic yield by a further 18 (32.7%) cases and giving an abnormal genetic test result in 42/55 (76.4%) fetuses overall. Pathogenic or likely pathogenic sequence variants in 14 different genes were detected across 18 fetuses. Seven genes are already listed in the International Skeletal Dysplasia Society Nosology and seven are not typically found to be causal for skeletal dysplasias and are not listed in the Nosology. CONCLUSIONS: In fetuses with skeletal system anomalies, chromosomal abnormality was the most common genetic diagnosis. Exome sequencing increased the diagnostic yield over that of CMA and polyploidy testing. Fetuses with skeletal abnormalities should undergo extended genetic testing following routine testing, as many genetic anomalies responsible for skeletal defects may otherwise be missed. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal complications in molecularly confirmed diandric and digynic triploid pregnancies: single institution experience and literature review.

OBJECTIVES: Assessment of the maternal complications in molecularly confirmed diandric and digynic triploid pregnancies. METHODS: Sonographic features, biochemical results, and clinical presentation were analyzed. Beta-hCG level was controlled after diandric triploidy. RESULTS: The study included nine diandric and twelve digynic triploid pregnancies at the mean gestational age at diagnosis of 14.9 and 18.0 weeks, respectively (p = 0.0391). Mean value of total-hCG was 979 703.6 U/ml in diandric cases and 5 455.4 U/ml in digynic ones (p < 0.000). Maternal complications occurred in 88.9% of diandric triploid pregnancies, including: thecalutein cysts (44.4%), hyperemesis gravidarum (44.4%), symptomatic hyperthyreosis (33.3%), early onset gestational hypertension (22.2%) and vaginal bleeding (11.1%). No case of proteinuria, preeclampsia or HELLP syndrome was observed. Only maternal complication observed in digynic triploidy was vaginal bleeding (50.0%). The mean time of beta-hCG normalization after diandric triploid pregnancies was 84 days (range 11-142 days). No case of gestational trophoblastic neoplasia (GTN) was observed. CONCLUSIONS: Maternal complications (except for vaginal bleeding) are associated with diandric triploidy. The relatively low incidence of hypertensive maternal complications and their less severe course in our cohort may be attributed to the earlier prenatal diagnosis. The frequency of GTN after diandric triploidy may be lower than previously reported.

Prenatal diagnosis of congenital myopathies and muscular dystrophies.

Congenital myopathies and muscular dystrophies constitute a genetically and phenotypically heterogeneous group of rare inherited diseases characterized by muscle weakness and atrophy, motor delay and respiratory insufficiency. To date, curative care is not available for these diseases, which may severely affect both life-span and quality of life. We discuss prenatal diagnosis and genetic counseling for families at risk, as well as diagnostic possibilities in sporadic cases.

First-trimester spontaneous pregnancy loss - molecular analysis using multiplex ligation-dependent probe amplification.

Spontaneous miscarriages are the most frequent complications of pregnancy and, in at least half of cases, are caused by chromosomal abnormalities, mainly aneuploidies. We present the preliminary results of the implementation of multiplex ligation-dependent probe amplification (MLPA) in the detection of chromosomal aberrations in the tissue derived from first-trimester miscarriage and evaluate the limitations and requirements of the method. We studied 181 MLPA analyses with subtelomeric and subcentromeric probe kits for all chromosomes (SALSA P070 and SALSA P181) performed on the first-trimester spontaneous miscarriage products in our Department of Genetics between September 2012 and December 2014. Conclusive MLPA results were obtained in 97.2% of samples. Chromosomal aberrations were detected in 40.3% of samples: 61.8% samples of good quality and 12.6% samples of poor quality (p < 0.001). The normal female karyotype was detected in 14.7% of good quality samples and 84.8% of poor quality samples (p < 0.001). MLPA is a useful tool for the detection of chromosomal aberrations in first-trimester miscarriage products. However, the tissue has to be well prepared before testing and the results 46,XX should be interpreted with caution.

[Prenatal diagnosis of a brain tumour--an example of diagnostic and therapeutical algorithm].

The authors describe their cooperation in the diagnosis and treatment of a newborn with malignant brain tumour (rare case of carcinoma of the choroid plexus) recognised by means of prenatal sonography and magnetic resonance. The case history is an example of modern algorithm of diagnostic and therapeutic procedures in perinatal medicine and the necessary multicentre collaboration.

Adenosine triphosphate for cardioversion of supraventricular tachycardia in two hydropic fetuses.

OBJECTIVE: We performed a retrospective study to check the effectiveness of adenosine triphosphate (Striadyne) for cardioversion of fetal supraventricular tachycardia (SVT) and to evaluate neonatal outcome after prenatal treatment of severe SVT with fetal hydrops. METHODS: Two hydropic fetuses with SVT were treated with Striadyne injection into the umbilical vein, as an additional treatment to the digoxin given intravenously to the mother. Both fetuses were in severe condition, with ultrasound, Doppler and laboratory signs of fetal distress and congestive heart failure. RESULTS: Sinus rhythm was obtained in both cases for different periods of time, without side effects of Striadyne. The children survived. There were severe cardiac and neurologic problems after delivery. CONCLUSIONS: Striadyne was an effective drug in converting SVT to the sinus rhythm in hydropic fetuses. Digoxin was useless in these fetuses in spite of the therapeutic level which was obtained in both mothers. We suppose that fetal SVT causing fetal hydrops could be the reason of brain damage, and intensive antiarrhythmic treatment seemed to be necessary.

[Open neural tube defects in prenatal diagnosis]. / Otwarta wada cewy nerwowej w diagnostyce prenatalnej.

The problem of open neural tube defects (ontd) is discussed in the light of results of prenatal tests performed in the district of Warsaw. These results seem to bear some epidemiological significance allowing estimation of approximate frequency of ontd as well as recurrence risk for the purpose of genetic counselling. Prenatal diagnosis of ontd is very important for individual families--particularly those with increased risk. However, in view of very small number of prenatal tests and the fact that maternal serum screening and ultrasonografic screening are practically not available the demographic impact of prenatal diagnosis in Poland on the frequency of ontd (and other genetic diseases) in Poland must be negligible.

[Diagnosis of human parvovirus B19 infection in nonimmune hydrops fetalis]. / Diagnostyka zakazenia ludzkim parwowirusem B19 w nieimmunologicznym obrzeku plodu.

Parvovirus B19 (PV B19) infection was investigated in 29 pregnant women with fetal hydrops, after exclusion of feto-maternal incompatibility within red blood cell antigens, TORCH infections, feto-maternal hemorrhage and genetics reasons. The active viral infection was detected in 9 women (31%) by PCR amplification of DNA B19; in 2 of them IgM and IgG, in 1 IgM and in 4 IgG antibodies were also present. In 6 women (20%) IgG antibodies were only found, but not IgM and DNA B19, which confirmed infection in the past. In addition in 9 cases DNA B19 was evaluated in the fetal blood. The results in the mothers and their fetuses were concordant (4 positive, 5 negative). Our conclusion is that in nonimmune hydrops fetalis, PV B19 infection should be based on the viral DNA evaluation in the blood of mother (or fetus). IgM antibodies, in time of fetal disorders, might not be detected.

[Early amniocentesis in prenatal diagnosis]. / Wczesna amniocenteza w diagnostyce prenatalnej.

In the period 1990-1991 483 prenatal diagnosis were carried out. Of those in 111 (23%) the technique of early amniocentesis was used, i.e. between 12th and 14th weeks of gestation. In 23 cases the result of cytogenetical diagnosis was positive. The time necessary for obtaining the result did not differ from that of amniocentesis performed at 15-20 weeks of gestation. The cytogenetical examination was successful in all cases of early amniocentesis.