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Functioning pituitary gonadotropinomas are rarely described and comprise only a small portion of pituitary adenomas. Most of them are macroadenomas and cause endocrine dysfunctions usually presenting as either ovarian hyperstimulation, testicular enlargement or precocious puberty. Transsphenoidal resection is currently regarded as the treatment of choice, while other treatment options are considered ineffective and are rarely used.

Neonatal leukaemia is a rare blood cancer occurring in baby less than 30 days of life is characterized by proliferation of white cells without known and obvious reasons. We report a case of a 7-day- old girl diagnosed with congenital leukaemia. At the time of presentation, she was evaluated as early neonatal sepsis. However, her laboratory investigations were consistent with B cell acute lymphoblastic leukaemia. Her cytogenetic analysis showed 46 XX trisomy 22, t(5,15) (p15,q15) and del 7 (q33,q35). She was managed with standard Interfant 06 protocol and had achieved marrow remission during the course of chemotherapy. Our case highlights the differentiation between lymphocytic leukemoid reaction and lymphoblastic malignant cells and also congenital acute lymphoblastic leukaemia who had a good outcome from the chemotherapy.

OBJECTIVE To assess the frequency of atypical chromosomal and submicroscopic anomalies, as well as fetal structural abnormalities, observed on first-trimester ultrasound scan in fetuses with nuchal translucency (NT) thickness > 99th centile, in order to evaluate the suitability of using standard cell-free DNA (cfDNA) testing as the sole screening test in these pregnancies. METHODS This was a retrospective cohort study of 226 fetuses with NT > 99th centile at 11-14 weeks' gestation, between January 2013 and December 2017, in a clinical setting in which greater than 95% of pregnant women receive first-trimester combined screening. All patients underwent genetic testing by means of quantitative fluorescence polymerase chain reaction and chromosomal microarray analysis, mainly in chorionic villus samples. We assessed the theoretical yield of two cfDNA testing models, targeted cfDNA (chromosomes 21, 18 and 13) and extended cfDNA (chromosomes 21, 18, 13 and sex chromosomes), and compared it with that of cytogenetic testing and ultrasound assessment in the first and second or third trimesters. RESULTS In the 226 fetuses analyzed, cytogenetic testing revealed 84 (37%) anomalies, including 68 typical aneuploidies (involving chromosomes 13, 18 or 21), six sex chromosome aneuploidies (four cases of monosomy X and two of trisomy X), three clinically relevant atypical chromosomal anomalies (one trisomy 22, one trisomy 21 mosaicism and one unbalanced translocation), five submicroscopic pathogenic variants and two cases with Noonan syndrome. Targeted and extended cfDNA testing would miss at least 12% (10/84) and 19% (16/84), respectively, of genetic anomalies, accounting for 4.4% and 7.1% of the fetuses with an increased NT, respectively. Finally, of the 142 fetuses with no identified genetic anomaly, a major fetal malformation was observed in 15 (10.6%) fetuses at the early anomaly scan, and in 19 (13.4%) in the second or third trimester. CONCLUSIONS cfDNA does not appear to be the appropriate genetic test in fetuses with NT > 99th centile, given that it would miss 12-19% of genetic anomalies in this group. Additionally, first-trimester ultrasound will identify a major structural abnormality in 11% of the fetuses with NT > 99th centile and no genetic anomaly. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Background: Chromosomal anomalies are a recognized cause of stillbirth, accounting for 6–17% of the cases. As a diagnostic laboratory method in this setting, conventional karyotyping has two main drawbacks: the need for viable fetal cells in a dead fetus and its limited resolution as compared to alternative techniques. Objective: To assess the effectiveness of cytogenetic analysis in stillbirths between different testing methods and different sampled tissues. Methods: From 2011 to 2017, 145 stillborn fetuses (defined as fetal losses after 22 weeks) were delivered in our center. The stillbirth protocol includes genetic testing by means of a karyotype, QF-PCR, or chromosomal microarray analysis (CMA), depending on the presence of fetal structural anomalies and the study time period. The success rates were compared between tests and between different sampled tissues. Results: Consent was granted for cytogenetic analysis in 136 stillbirths. Test success rate was 100% (38/38) for CMA independent of the sampled tissue, 99% (65/66) for QF-PCR, and 66% (65/98) for karyotyping. The success rate for karyotyping was 48% (69/145) of the total tissues samples, showing great variation according to the tissue sampled: 83% (40/48) in amniotic fluid, 78% (21/27) in the placenta, 13% (7/54) in fetal skin, and 6.3% (1/16) in fetal blood. Four full or partial aneuploidies (trisomy 9, trisomy 22, tetrasomy 18p, and monosomy X) and 2 microdeletions (del2p16.3 and del1q13.2q13.4) were found, resulting in a 3.9% (4/103) prevalence for full or partial aneuploidy and a 5.3% prevalence (2/38) for submicroscopic abnormalities. Conclusions: Amniotic fluid should be the preferred tissue source in the cytogenetic analysis of stillbirth due to its high success rate. Between tests, CMA is a preferable method because of its higher test success rate, independent of the sampled tissue, and higher diagnostic yield including chromosomal and submicroscopic anomalies.

Nowadays the problem of recurrent miscarriage is relevant. 17-20% of all registered pregnancies end with inevitable miscarriages. 80% of them are early pregnancies and in most cases represent missed abortions. Besides, one of the leading cause of missed abortion are chromosomal abnormalities. Analyzed the clinical and anamnestic data of patients, diagnosed with missed abortion during early pregnancy, examined in Saint-Petersburg in 2005-2006 and 2015-2017: patients with normal chorion karyotype and patients with chromosomal abnormalities of the chorion. Revealed that the prevailing chromosomal abnormality is aneuploidy, among all types of aneuploidy the most frequently are trisomy 16, trisomy 13, trisomy 22 and trisomy 21. The structure of aneuploidy has changed in 10-11 years. Now, in comparison with 2005-2006, at missed abortion the trisomy 16 in chorionic villi is found 3.8 times more often, the trisomy 13 is found 2.8 times more often and the trisomy 22 is found twice less often (p

Chromosomal aberrations such as parental balanced translocation contribute to a significant proportion of recurrent pregnancy losses. These have extreme genetic implications on the foetus which can either cause physical and/or mental retardation or early death. In this study, we report a unique clinical case of a couple with three consecutive pregnancy losses and we aim to determine the genetic abnormalities causing the miscarriages. Conventional cytogenetic and molecular genetic analysis were performed on the products of conception as well as for the parents. Chromosomal analysis was performed based on the ISCN 2016 guidelines. This was followed by Chromosomal microarray analysis carried out using ISCA consortium probe set (8X60K). Genetic testing for the 1st product of conception was not performed. However, the 2nd and 3rd products of conception indicated an autosomal trisomy 22 and a 3.7 Mb deletion of 2p (cytoband p25.3) along with 13.6 Mb duplication of 16p (cytoband p13.3p13.12), respectively. The paternal karyotype was normal but mother showed a balanced translocation 46,XX,t(2;16)(p25.3;p13.3). This was parallel to the products of conception microarray findings, unbalanced chromosomal abnormality in the foetus. Balanced translocation carriers are susceptible for meiotic nondisjunction processes and early detection of genetic anomalies can be informative to parents trying to conceive. Genetic analysis of the abortus after the 1st loss can be helpful to understand the cause of miscarriage. A combined approach with microarray and karyotyping of the products of conception can be important to determine the specific aberrations in the foetal chromosomes leading to abortion.

Introducción. El tamizaje ecográfico del primer trimestre se realiza en el Perú desde hace 19 años, pero se carece de información del seguimiento de las pacientes evaluadas. Objetivos. Determinar el pronóstico de una translucencia nucal (TN) muy aumentada en el feto. Diseño. Estudio retrospectivo observacional. Pacientes. Se evaluó 10 340 fetos consecutivos entre las 11 y 13 semanas, en madres que llegaron al servicio de ecografía. Intervenciones. Evaluación por nueve ecografistas acreditados por la Fetal Medicine Foundation (FMF) siguiendo las recomendaciones de la FMF. Los resultados fueron registrados en el software Astraia. Resultados. Treintaisiete (0,36%) pacientes tuvieron TN ≥ 5,5 mm; ocho no regresaron a la institución y se desconoce el desenlace de su embarazo, por lo que no fueron considerados en el análisis posterior. De los 29 reportados, en 18 se realizó cariotipo prenatal, 17 de ellos fueron anormales (7 trisomías 21; 4 trisomías 18; 5 monosomías X; una trisomía 22). Cuatro de los 7 fetos con trisomía 21 nacieron a término sin malformaciones importantes; uno falleció durante el embarazo, otro embarazo fue interrumpido en el extranjero y se desconoce el desenlace de un caso. De los 11 que no se realizaron cariotipo prenatal, uno (3,2%) nació vivo y sano y los otros 10 fallecieron durante el embarazo. Diecisiete cariotipos de 19 conocidos fueron anormales, lo que difiere significativamente de los resultados de Kagan (89% vs 64%, p

Objective: We present prenatal diagnosis of mosaic trisomy 22 at amniocentesis in a pregnancy with facial cleft, oligohydramnios and intrauterine growth restriction (IUGR), and we review the literature. Case report: A 37-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+22[9]/46,XX[9]. Array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes showed a result of arr(22) × 3 [0.8]. Prenatal ultrasound revealed fetal median facial cleft, oligohydramnios and IUGR. Repeat amniocentesis at 22 weeks of gestation using uncultured amniocytes revealed an aCGH result of arr 22q11.1q13.33 (17,397,498–51,178,264) × 2.8 compatible with 80% mosaicism for trisomy 22, and a fluorescence in situ hybridization (FISH) result of mosaic trisomy 22 with trisomy 22 in 54/100 interphase cells. The cultured amniocytes at repeat amniocentesis had a karyotype of 47,XX,+22[12]/46,XX[8]. The parental karyotypes were normal. Polymorphic DNA marker analysis confirmed a maternal origin of the extra chromosome 22. The pregnancy was terminated, and a 256-g female fetus was delivered with facial dysmorphism and median facial cleft. Cytogenetic analysis of the skin fibroblasts revealed a karyotype of 47,XX,+22[33]/46,XX[7]. Conclusion: Fetuses with high level mosaicism for trisomy 22 at amniocentesis may present IUGR, facial cleft and oligohydramnios on prenatal ultrasound. Keywords: Amniocentesis, Mosaic trisomy 22, Prenatal diagnosis, Ultrasound

Objectives Emanuel syndrome is a rare inherited syndrome, a correct in utero diagnosis allows effective management for ongoing and future pregnancies. Case presentation Here, we report a case of a complete non-mosaic trisomy 22, with several prenatal sonographic findings, that was diagnosed in utero at 15 weeks’ gestation and then it was confirmed with chromosomal analysis and postmortem examination. Conclusions Every anatomical difference should always be further investigated in order to achieve the correct diagnosis.

Background: Around 70% of all pregnancies (Including 15% of clinically-recognized ones) are lost due to various fetal or maternal disorders. Chromosomal aneuploidies are among the most common causes of pregnancy loss. Standard chromosome analysis using G-banding technique (Karyotype) is the technique of choice in studying such abnormalities; however, this technique is time-consuming and sensitive, and limited by vulnerabilities such as cell culture failure. The use of molecular cytogenetic techniques, including array-based techniques and Multiplex Ligation-Dependent Probe Amplification (MLPA), has been proposed to overcome the limitations of this method to study the products of conception. This study has been designed to investigate the feasibility of using MLPA technique as a standalone genetic testing, with histopathologic examinations and genetic counseling to detect aneuploidies in products of conception and neonatal deaths. Methods: Forty-two verified fetal and neonatal samples were studies and genetic counseling was scheduled for all parents. Histopathologic examinations were carried out on the products of conception, and appropriate fetal tissues were separated for genetic studies. Following DNA extraction and purification, MLPA was carried out to investigate chromosomal aneuploidies. Results: Nine samples (21.42%) were diagnosed to be affected with aneuploidy. Detected aneuploidies were trisomy 22 (n=3), trisomy 21(n=1), trisomy 18 (n=2), trisomy 16 (n=1), trisomy 13 (n=1), and monosomy of chromosome X (n=1). The MLPA analysis results were conclusive for all of the fetal samples (Success rate: 100%). Conclusion: These results suggest that MLPA, as a standalone genetic testing, is an accurate, rapid, and reliable method in overcoming the limitations of standard cytogenetic techniques in genetic investigation of products of conception.

Acute myeloid leukemia (AML) with inv(16) is primarily associated with the eosinophilic LAM4 form belonging to the favorable prognosis group of AML. We report the case of an 18-year-old man with acute myeloid leukemia with unusual inversion of chromosome 16. Cytological, phenotypic and cytogenetic investigations showed a divergence from those in the literature. Indeed, the myelogram shows a medullary infiltration by elements blocked at the stage of myeloblates/promyelocytes, containing Auer rods grouped sometimes in fagots in blasts, promyelocytes and neutrophils. In view of this pathognomonic aspect, the diagnosis of AML type M3 is mentioned but quickly questioned by the results of immunophenotyping in favor of a maturing AML (M2). The karyotype and the FISH later objectify a recurrent anomaly "cytologically unexpected" inversion 16 (p13, q22) associated with trisomy 22.

Literature reports of placental mosaicism, including trisomy 22, were analyzed. The chance of correlation of placental aneuploidy with fetus aneuploidy, also the probability of complications in pregnancy and fetal growth restriction and postnatal patients growth in the cases of confined placental mosaicism, were demonstrated. The case of prenatal diagnosis of confined placental mosaicism of trisomy 22 with favorable outcome is presented. The necessity of cytogenic assay of amniocytes and fetal lymphocytes in the case of placental heteroploidy diagnosis was emphasized.

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.1% vs 41.1%, P = .026). Patients with secondary cytogenetic abnormalities had longer overall survival (OS) than those without abnormalities (median 190 vs 87 months, P = .021); trisomy 8, trisomy 22, and loss of the X or Y chromosome were associated with longer OS. In the 165 cases performed of targeted gene sequencing, pathogenic mutations were detected in 75.7% of cases, and were more frequent in de novo than in therapy-related disease (P = .013). Mutations were found in N/KRAS (37.0%), FLT3 (27.8%), KIT (17.2%), TET2 (4.9%), and ASXL1 (3.9%). The TET2 mutations were associated with shorter OS (P = .012) while N/KRAS mutation was associated with longer OS in t(8;21) AML patients (P = .001). The KIT mutation did not show prognostic significance in this cohort. Although they received similar therapy, t-CBF-AML patients had shorter OS than de novo patients (median 69 vs 190 months, P = .038). In multivariate analysis of all patients, older age and absence of any secondary cytogenetic abnormalities were significant predictors of shorter OS. Among the t-CBF-AML subset, age and hemoglobin were significant on multivariate analysis. This study demonstrated that although de novo and t-CBF-AML patients share many features, t-CBF-AML patients have worse clinical outcome than de novo patients.

Objective Non‐invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed. Method NIPT was conducted in the course of the Dutch TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core of two to four placental chorionic villi biopsies were studied with single nucleotide polymorphism (SNP) array. Clinical outcome data were collected. Results In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three cell lines were present in the placenta, whereas BPD was found in AF. In 1/3 cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was found in the placenta. Five of 10 pregnancies were affected with pre‐eclampsia, low birth weight, preterm delivery, and/or congenital malformations. Conclusion The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated proves that trisomic zygote rescue may involve multiple rescue events during early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may explain the abnormal phenotype in undiagnosed cases., What's already known about this topic? Trisomic zygote rescue is the main mechanism for uniparental disomy (UPD) formation.Confined placental mosaicism (CPM) is the major source of discordant NIPT results.CPM is associated with a risk for adverse pregnancy outcome. What does this study add? Trisomic zygote rescue may involve multiple rescue events based on the co‐occurrence of a trisomy‐, UPD‐, and BPD‐cell line in half of the rescued cases as revealed by placental studies.

The authors report a case of mosaic trisomy 22 diagnosed antenatally by amniocentesis at 19 weeks. The ultrasound finding was an isolated posterior fossa fluid collection in the brain with features possibly suggestive of a Blake’s Pouch cyst with doubtful hypoplasia of cerebellar vermis. The karyotype of the amniocytes was mos47, + 22[6]/46[8] with two separate clones of cells. Trisomy 22 was seen in one clone (43%) while the other clone (57%) had a normal karyotype. On postnatal examination after termination, there were no dysmorphic features. A selective autopsy of the fetal brain was suggestive of normal posterior fossa anatomy with normal cerebellar vermis which retrospectively confirmed the diagnosis of a Blake’s pouch cyst.

Trisomy 22 is very rare in live-borns with a frequency of 1 in 30,000 to 50,000, but it is the second most common autosomal trisomy, after trisomy 16, present in miscarriages, accounting for 3% to ...

We aimed to determine the relationship between fetal chromosomal abnormalities and maternal age among spontaneous first trimester abortions in women in Northeast China.We evaluated 497 chorionic villi samples from patients with a history of spontaneous abortion during the first trimester. We divided the samples into five groups according to the maternal age:25, 25-29, 30-34, 35-39, and ≥40 years. We identified chromosomal abnormalities by fluorescence in situ hybridization.Among the 497 chorionic samples of spontaneous abortion, 180 (36.22%) had fetal chromosomal abnormalities. Patients aged ≥40 years had a significantly higher percentage (60.61%) of fetal chromosomal abnormalities compared with the other groups. More women in the ≥40 and 35- to 39-year groups had a history of three consecutive miscarriages and 10 kinds of abnormalities. The most frequent aneuploidy was trisomy 22, followed by trisomy 16.These results revealed that the kinds of fetal abnormalities, numbers of abortions, and chromosomal abnormality rates increased with increasing maternal age. The most common trisomy types in spontaneous abortions were closely related to maternal age. We hypothesize whether the larger probability of chromosomal abnormalities is due to increased mutation rate with maternal age, or due to a worse in-utero conditions.

We report a case of chimpanzee trisomy 22 in a captive-born female. Because chromosome 22 in great apes is homologous to human chromosome 21, the present case is analogous to human trisomy 21, also called Down syndrome. The chimpanzee in the present case experienced retarded growth; infantile cataract and vision problems, including nystagmus, strabismus, and keratoconus; congenital atrial septal defect; and hypodontia. All of these symptoms are common in human Down syndrome. This case was the second reported case of trisomy 22 in the chimpanzee. The chimpanzee in our case became blind by 7 years old, making social life with other chimpanzees difficult, but opportunities to interact with other conspecific individuals have been offered routinely. We believe that providing her with the best care over the course of her life will be essential.

The BACs-on-Beads™ (BoBs™) assay was a multiplex, bead-based suspension array using microspheres with two distinct infra-red and red fluorochromes to generate more than 100 different unique probes....

Fetal chromosomal abnormalities are considered to be the main cause of spontaneous abortion (SA). We aimed to determine the differences in the rates and numbers of chromosomal abnormalities between samples from women with a history of one versus more than one SA as well as between samples from first- and second-trimester SAs in women from Northeast China. In total, 1210 products of conception (POCs) from patients with a history of one or more SAs were examined. Of these 1210 samples, 434 were from women with a history of 1 SA, and 776 were from women with a history of more than 1 SA. Additionally, 1071 samples were from the first trimester, 118 were from the second trimester, and 21 were from the third trimester. We identified chromosomal abnormalities by next-generation sequencing (NGS) technology. Among the 1210 POCs in women with SA, 607 (50.17%) had fetal chromosomal abnormalities. There were no significant differences in the rates of chromosomal abnormalities according to the abortion frequency. However, first-trimester SA had a significantly higher percentage of fetal chromosomal abnormalities than second-trimester SA (P

Background: Cases of non-mosaic liveborn Trisomy 22 infants are rare in the literature. The reported lifespan of complete, non-mosaic Trisomy live births range from minutes to 3 years, though the majority rarely live past the first 2 weeks. Cases with longer-term survival are not typically associated with severe cardiac anomalies. Many centers do not offer cardiac surgery for infants with Trisomies 13 and 18, though this landscape is currently evolving. For those who have undergone congenital heart surgery, …

To determine the true- and false-positive rates of cf-DNA testing in a cohort of patients from tertiary care centers and assess the impact of ultrasound examinations in pregnancy management. Clinical, cytogenetic and ultrasound data of 101 consecutive fetuses were collected retrospectively. Cases were classified into five groups according to the ultrasound findings. Karyotyping, interphase FISH and microarray techniques were used for follow-up studies. The overall false-positive rate was low for trisomy 21 (T21, 8.2 %), but significantly higher for trisomy 18 (T18, 40 %), monosomy X (MX, 50 %), X/Y trisomies (57.1 %), trisomy 13 (T13, 71.4 %). While single cases of trisomy 16, trisomy 22 and 8q duplication positive in cf-DNA were confirmed, 3 microdeletions (1p36 and two 22q11.2) were not. About 75 % of confirmed T21's and all confirmed T18 and T13 had major markers and/or malformations. While false-negative cases (two T21, one T18 and one T13) were identified due to abnormal ultrasound findings, all false-positive cases were normal sonographically. Ultrasound findings of confirmed trisomy 16, 22, dup8q, monosomy X and other X/Y aneuploidies were unspecific. Term placenta studies were helpful to assess the role of confined mosaicism in unconfirmed cf-DNA test results. A vanishing twin has been observed as the likely cause of one false-positive T18. Our study contributes clinical data on discrepant cf-DNA testing results, corroborates the need for confirmational invasive testing and underscores the benefit of expert ultrasound in the prevention of fatal diagnostic errors. Ermittlung der Korrekt- und Falsch-Positiv-Rate von NIPT bei Patienten eines Zentrums der Tertiärversorgung sowie des Nutzens von Ultraschalluntersuchungen im Schwangerschaftsmanagement. Klinische, zytogenetische und Ultraschalldaten von 101 konsekutiven Schwangerschaften wurden retrospektiv ausgewertet. Abhängig vom Ultraschallbefund wurden diese in fünf Gruppen unterteilt. Für Nachfolgestudien wurden Karyotypisierung, Interphasen-FISH und Microarray-Techniken verwendet. Die Falsch-Positiv-Rate für Trisomie 21 war niedrig (T21, 8,2 %), jedoch deutlich höher für Trisomie 18 (T18, 40 %), Monosomie X (MX, 50 %), XXY, XXX, XYY (57,1 %) und Trisomie 13 (T13, 71,4 %). Während Einzelfälle für Trisomie 16, Trisomie 22 und 8q Duplikation bestätigt werden konnten, war dies für 3 Mikrodeletionen (1p36 und zwei 22q11.2) nicht der Fall. Etwa 75 % der bestätigten T21 und alle bestätigten T18 und T13 hatte auffällige Ultraschallbefunde. Alle falsch-negativen Fälle (zwei T21, ein T18 und ein T13) wurden aufgrund von auffälligen Ultraschallbefunden identifiziert, dagegen waren alle falsch-positiven Fälle sonografisch unauffällig. Die Ultraschallbefunde bei bestätigter Trisomie 16, Trisomie 22, Dup8q, Monosomie X und andere X/Y-Aneuploidien waren unspezifisch. Nachfolgende Plazentauntersuchungen waren hilfreich, um die Rolle von plazentalen Mosaiken in den Fällen mit falsch-positiver Testung zu beurteilen. Ein vanished twin war die wahrscheinliche Ursache eines falsch-positiven Trisomie18-Befundes im NIPT. Unsere Studie liefert weitere klinische Daten zu nicht bestätigten cf-DNA-Testergebnissen, bekräftigt die Notwendigkeit eines invasiven Tests zur Bestätigung und unterstreicht die Bedeutung von spezialisierten Ultraschalluntersuchungen zur Vermeidung von fatalen diagnostischen Fehlern.

Background: Trisomy 22 mosaicism is a rare autosomal anomaly with survival compatibility. Recognition of the complete trisomy 22 which is incompatible with life from the mosaic form is critical for genetic counseling. Affected mosaic cases have prevalent clinical presentations such as webbed neck, developmental delay, abnormal ears, cardiac disorders, and microcephaly. Phenotype of these patients is milder than full chromosomal aneuploidy, and the severity of the phenotype depends on the count of trisomic cells. We describe a 4-year-old boy with mosaic trisomy 22 from healthy parents and no family history of any genetic disorders in the pedigree. Method and Results: The patient had determined dysmorphic clinical features including facial asymmetry, cleft palate, gastroenteritis, hydronephrosis, developmental delay, genital anomalies, dysplastic toenails, flattened nasal bridge, congenital heart defect, hearing loss, cryptorchidism, and hypotonic muscle. He is the first reported with hypothyroidism and larynx wall thickness in worldwide and the first with atrial septal defect (ASD) from Iran. Chromosomal analyses using G-banding indicated a de novo Mos 47,XY,+22(6)/46,XY(44) karyotype with no other chromosomal structural changes. Conclusions: Our observations confirm the importance of cytogenetic analyses for determining the cause of congenital anomalies and provide a useful genetic counseling. In addition, due to the fact that some of mosaic trisomy 22 features are unavoidable such as CHD and general hypotrophy, we suggest including echocardiography test for early diagnosis during the clinical assessment. © 2018 Wiley Periodicals, Inc.

Objective Noninvasive prenatal testing (NIPT) can assess chromosomes other than 13, 18, 21, X and Y. These rare autosomal trisomies (RATs) can adversely affect pregnancy outcome. Methods A prospective study of NIPT using the Illumina sequencing platform assessing all chromosomes were reported for further management. Results There were 28 RATs identified in 23 388 samples (one in 835), the most common being trisomy 7 (n = 6), followed by trisomy 16 (n = 4) and trisomy 22 (n = 3). Abnormal outcomes occurred in 16 cases: miscarriage (n = 6), true fetal mosaicism (n = 5), and fetal structural anomaly on ultrasound (n = 5). Growth restriction was seen in eight cases and correlated with very low‐pregnancy‐associated plasma protein‐A levels. Two of the 17 live born babies had a structural anomaly, and one had a phenotype similar to mosaic trisomy 16 despite a normal microarray result. Conclusion Rare autosomal trisomies are not rare and often associated with poor obstetric outcomes. They should be discussed with the clinician to guide management. Pregnancy outcomes varied by chromosome being generally favourable for some (eg, trisomy 7) and poor for others (eg, trisomy 22). In the presence of a RAT, pregnancy‐associated plasma protein‐A is predictive of placental dysfunction and fetal growth restriction.

Background: Genetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH) using probes for 13, 16, 18, 21, 22, X and Y chromosomes. Methods: A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion. Results: A total of 832 samples were finally analyzed. 368 (44.23%) were abnormal, in which 84.24% (310/368) were aneuploidies and 15.76% (58/368) were polyploidies. The first was trisomy16 (121/310), followed by trisomy 22, and X monosomy. There was no significant difference in the rate of aneuploidy in the advanced maternal age group (≥35 years old) and young maternal age group (

Objective We present the application of non-invasive prenatal testing (NIPT) in late gestation in a pregnancy associated with intrauterine growth restriction (IUGR) and trisomy 22 confined placental mosaicism (CPM). Case report A 35-year-old pregnant woman underwent chorionic villus sampling (CVS) at 12 weeks of gestation. The pregnancy was conceived by in vitro fertilization and intracytoplasmic sperm injection. CVS revealed a karyotype of 47,XY,+22 in all of 15 cultured chorionic villi cells. Array comparative genomic hybridization analysis on uncultured chorionic villi revealed a result consistent with trisomy 22. The woman underwent amniocentesis at 17 weeks of gestation. Amniocentesis revealed a karyotype of 46,XY in all 20 colonies of cultured amniocytes. Additional polymorphic DNA marker analysis excluded uniparental disomy 22. The parental karyotypes were normal. Prenatal ultrasound at 23 weeks of gestation revealed fetal retrognathia, IUGR and a calcified placenta. NIPT at 27 weeks of gestation using maternal plasma cell-free DNA analysis showed a chromosome Z-score of 5.74 for chromosome 22 (the Z-score for each pair of chromosomes is defined as “increased” if >3), indicating an abnormal placenta with trisomy 22 CPM leading to IUGR in the fetus. At 36 weeks of gestation, a 1754-g male fetus was delivered with cleft palate and imperforate anus but no other phenotypic abnormalities. The cord blood had a karyotype of 46,XY (40/40 cells), the umbilical cord had a karyotype of 47,XY,+22[9]/46,XY[31], and the placental tissues had a karyotype of 47,XY,+22[15]/46,XY[25]. Conclusion NIPT in late gestation is useful in detection of placental abnormality associated with CPM and IUGR but a normal karyotype at amniocentesis.