In-house genetic counseling increases the detection of abnormal karyotypes-a 26-year experience in prenatal diagnosis in a single tertiary referral hospital in Poland.

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.

Prenatal diagnosis and clinical significance of cephalocele-A single institution experience and literature review.

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.

Complex malformations involving the fetal body wall - definition and classification issues.

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.

Triploidy - variability of sonographic phenotypes.

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.

Targeted prenatal diagnosis of Pallister-Killian syndrome.

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.

[Non-invasive prenatal diagnosis of the most common aneuploidies with cell-free fetal DNA in maternal serum--preliminary results]. / Nieinwazyjna diagnostyka prenatalna najczestszych aneuploidii na podstawie plodowego DNA we krwi matki --doniesienie wstepne.

OBJECTIVES: The aim of the study was to present initial results of non-invasive prenatal diagnosis of common aneuploidies of chromosomes 21, 18 and 13 based on cell-free fetal DNA in maternal serum in high-risk patients, and to compare the results with routine karyotyping. MATERIAL AND METHODS: Before the invasive procedure, 10 ml of peripheral blood from 10 patients was collected to isolate cell-free fetal DNA and to perform a non-invasive fetal trisomy test (NIFTY provided by Beijing Genomics Institute, BGI, Shenzen, China). RESULTS: Three out of 10 samples showed an abnormal karyotype in traditional karyotyping. There were 9 conclusive NIFTY results. NIFTY detected 1 out of 2 trisomies 18. The quantity of cell-free fetal DNA in maternal plasma in the second probe with trisomy 18 was unsatisfactory fora conclusive NIFTY result. In 1 case traditional karyotyping revealed mosaicism impossible to detect with NIFTY

[Effectiveness of multiplex ligation dependent probe amplification (MLPA) in prenatal diagnosis of common aneuploidies]. / Analiza efektywnosci techniki MLPA w inwazyjnej diagnostyce prenatalnej najczestszych aneuploidii.

OBJECTIVES: To assess the effectiveness of the MLPA method (multiplex ligation dependent probe amplification) in prenatal diagnosis of common aneuploidies and compare its concordance with traditional karyotyping. MATERIAL AND METHODS: From October 2008 until July 2012 we performed 195 MLPA (MRC-Holland) tests with the P095 probe mix on DNA extracted from chorionic villi or amniotic fluid from pregnant women with elevated risk for abnormal fetal karyotype and 5 tests on miscarriage DNA samples. Cell culture and traditional karyotyping were performed in parallel. RESULTS: Traditional karyotyping was successfully performed in 192 cases (98.5%; 192/195). In 52 cases the fetal karyotype was abnormal (26.8%). The most common findings included aneuploidies of the following chromosomes: 13, 18, 21, X, Y (86.5%, 45/52). There were 179 conclusive and 1 inconclusive MLPA result (92.3%; 180/195). The absolute specificity and sensitivity of the MLPA test were 100%. In 9 cases traditional karyotyping revealed aberrations impossible to detect with the MLPA P095 kit. The MLPA reaction was successfully performed on all miscarriage DNA samples. CONCLUSIONS: MLPA is an effective method for detecting common aneuploidies. Its effectiveness for miscarriage DNA samples remains to be elucidated in further studies.

[Increased nuchal translucency in chromosomally normal fetuses and pregnancy outcomes--a retrospective study]. / Przeziernosc karku powyzej 3,5 mm u plodów z prawidlowym karfiotypem--analiza wyników ciaz.

OBJECTIVES: The objective was to study the outcomes of fetuses with increased nuchal translucency > or = 3.5 mm and normal karyotype. MATERIALS AND METHODS: We performed a retrospective study on pregnancy outcomes and children development in 87 women with increased fetal nuchal translucency and normal karyotype who underwent chorionic villus sampling at our department. Mean observation period was 12 months after birth. Adverse pregnancy outcome was defined as miscarriage and intrauterine fetal demise, termination of pregnancy structural defect, neonatal death, genetic syndrome and other major abnormalities. RESULTS: The total incidence of adverse pregnancy outcome was 39.1% (n = 34). The likelihood of an adverse pregnancy outcome, a major structural defect or major heart defect increased significantly with nuchal translucency (OR 3.77). 68 children (78.2%) were born alive. Nuchal translucency was significantly higher in newborns with adverse pregnancy outcome than in healthy children [4.1 mm vs. 5.7 mm; p < 0.01]. After a normal anomaly scan at 20 weeks gestation the risk of adverse outcome was 14.5% (n = 9, 9/62) and increased with nuchal translucency thickness from 10.2% for NT 3.5-4.4 mm to 100% for NT > or = 6.5 mm [p < 0. 0 1]. There was no significant relationship of fetal gender maternal age and persistence of the nuchal fold with adverse pregnancy outcome. The rate of neurodevelopmental delay was 3.4 % and was not higher than in the general population. CONCLUSIONS: The overall risk of adverse pregnancy outcome was around 40% and was related to nuchal translucency thickness. After excluding structural defects, the chance of a favorable outcome was 85%. The rate of neurodevelopmental delay in fetuses with increased nuchal translucency normal karyotype and normal anatomy is not higher than in the general population.

[A study on the occurrence of the deletion 22q11.2 in patients affected with a psychiatric disease]. / Badania nad wystepowaniem delecji 22q11.2 u osób z choroba psychiczna.

AIM: The aim of the study was an estimation of the rate of deletion 22q11.2 among psychiatric patients and an attempt at the assessment of the degree in which this rate is influenced by the coexistence of dysmorphic features and congenital defects. METHODS: Cytogenetic examination was performed in 255 patients with psychosis. Patients were divided into two groups. Group I was composed of 61 patients with psychosis and at least two phenotypic features characteristic of 22q11.2 deletion syndrome (22q11DS), group II was composed of 194 patients with psychosis without phenotypic features of 22q11DS. Banding and fluorescence in situ hybridization (FISH) techniques were applied. RESULTS: 22q11.2 deletion was found in 3/61 patients of group I (4.9%) and in 3/255 among all psychiatric patients (1.2%). This incidence was significantly higher than in the general population (p < 0.001). The frequency of the deletion was even higher among psychiatric patients revealing phenotypic features of 22q11DS: 3/61 (4.9%) (p < 0.0001). In all the cases with the deletion, the phenotype features were characteristic of 22q11DS. Three other psychiatric patients had sex chromosomes' aberrations: 47, XYY, 47, XXY and 47, XXX. Moreover one case of balanced translocation t(2;10) (q10; q10) was detected. Conclusions. (1) 22q11.2 deletion was found to be 40 times more common among psychiatric patients than in the general population; sex chromosome aberrations are also significantly more common than in the general population. (2) The presence of dysmorphic features and some congenital defects in psychiatric patients increases the rate of deletion 22q11.2 significantly.

[Cytogenetic-molecular analysis of balanced chromosomal rearrangements in nine patients with intellectual disability, dysmorphic features and congenital abnormalities]. / Cytogenetyczno-molekularna charakterystyka zrównowazonych rearranzacji chromosomowych u dziewieciu pacjentów z cechami uposledzenia umyslowego, dysmorfii oraz wadami rozwojowymi.

INTRODUCTION: In about 6% of individuals with intellectual disability, dysmorphic features and congenital anomalies, an abnormal, apparently balanced karyotype is found. These abnormalities may result from abnormal expression of genes at the breakpoints, presence of a submicroscopic deletion, or other unbalanced chromosome aberrations. In such cases, the detailed analysis of breakpoints of balanced chromosome rearrangements may help with identification of genes responsible for patient's clinical features. AIM OF WORK: Was the explanation of causes of abnormal phenotype in the carriers with abnormal but balanced karyotype. MATERIAL AND METHODS: Cytogenetic-molecular analysis performed in nine patients with mental retardation, dysmorphic features and congenital anomalies. Studies with subtelomeric probes, high resolution comparative genomic hybridization (HR-CGH) and fluorescence in situ hybridization (FISH) with region-specific BAC clones were performed. RESULTS: Seventeen chromosome breakpoint regions were narrowed to 200-400 kb. In one case, an 0.5-Mb submicroscopic deletion associated with more complex rearrangement has been found. Mapping of the breakpoints and information obtained from the UCSC Human Genome Browser data base enabled identification of 46 genes in these regions. Twelve genes, that may have been disrupted as a result of the patients' chromosomal rearrangement, were found. At four different breakpoints the identified genes (NRCAM, NPTX1, NMT1, MAPT, HDAC5 and MEF2C) may be due to a position effect. CONCLUSIONS: The results confirm earlier suggestions concerning reasons of abnormal phenotype in the patients with balanced chromosome rearrangements and present the value of detailed analysis of the genome in such cases.