Array-comparative Genomic Hybridization Results in Clinically Affected Cases with Apparently Balanced Chromosomal Rearrangements.

Carriers of apparently balanced chromosomal rearrangements (ABCRs) have a 2-3-fold higher risk of carrying an abnormal phenotype, when compared to the average population. Apparently balanced chromosomal rearrangements can be imbalanced at the submicroscopic level, and changes in the gene structure, formation of a new chimeric gene, gain or loss of function of the genes and altered imprinting pattern may also affect the phenotype. Chromosomal microarray (CMA) is an efficient tool to detect submicroscopic imbalances at the breakpoints as well as in the whole genome. We aimed to determine the effectiveness of array-comparative genomic hybridization (aCGH) application in phenotypically affected cases with ABCRs at a single center from Turkey. Thirty-four affected cases (13 prenatal, 21 postnatal) carrying ABCRs were investigated with CMA. In postnatal series, ABCRs were familial in 7 and de novo in 14 cases. Seven de novo cases were imbalanced (in postnatal series 33.3% and in de novo cases 50.0%). Out of 13 prenatal cases, five were familial and eight were de novo in origin and two de novo cases were imbalanced (in 15.4% prenatal series and in 25.0% de novo cases). No cryptic imbalance was observed in familial cases. The anomaly rates with array studies ranged between 14.3-25.0% in familial and between 20.0-57.5% in de novo cases of postnatal series in the literature. Studies focused on prenatal ABCR cases with abnormal ultrasound findings are limited and no submicroscopic imbalance was reported in the cohorts. When de novo postnatal or prenatal results were combined, the percentage of abnormalities detected by CMA was 40.9%. Taking this contribution into consideration, all ABCRs should be investigated by CMA even if the fetal ultrasound findings are normal.

Detection of fetal RHD pseudogene (RHDΨ) and hybrid RHD-CE-Ds from RHD-negative pregnant women with a free DNA fetal kit.

Hemolytic disease of the newborn is a clinical condition in which maternal and paternal Rh blood group antigens are incompatible and the mother is negative for the antigen whereas the father is positive. Analysis of fetal cells recovered from maternal plasma can provide a highly sensitive prenatal diagnosis. The fetal RHD gene in plasma DNA is detected by real-time PCR amplification of two different segments of the RHD gene (exons 7 and 10). Each amplicon is revealed with specific probes. We examined 40 female blood samples to verify the specificity of RHD exons (7 and 10) amplified by real-time PCR. Thirty fetuses were predicted to be RHD-positive based on analysis of plasma DNA. Seven fetuses were predicted to be RHD-negative. One fetus was negative for RHD on exon 10, and positive for RHD on exon 7 (early gestation age); two fetuses were RHD-negative on exon 7, and RHD-positive on exon 10 (RHD-CE-D(s) or RHDΨ), indicative of a maternal RHD allele. We conclude that it is necessary to analyze at least two exon regions in the RHD gene.

Serum microRNA expression in pregnancies with preeclampsia.

Preeclampsia continues to be a mortal disease of pregnant women throughout the world. Recently, geneticists, allied with obstetricians, have opened new frontiers. MicroRNAs (miRNAs) are members of a class of small, noncoding RNA molecules. They are critical posttranscriptional regulators of gene expression. We extracted circulating miRNA from maternal plasma and quantified mir-152 and mir-210. We found up-regulated miR-210 levels as well as down-regulated mir-152 levels in preeclampsia patients.We propose that detection of increased mir-210 levels in maternal serum could be used to improve prediction methods for noninvasive prenatal diagnosis of preeclampsia.

Intracranial ultrasound abnormalities and fetal cytomegalovirus infection: report of 8 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate fetal intracranial and other ultrasonographic findings in cytomegalovirus (CMV) infection. METHODS: Data on amniotic fluid CMV-DNA-PCR-positive pregnancies detected in our institution between January 2006 and June 2009 were reviewed retrospectively. Fetal biometric measurements, fetal anatomy, amniotic fluid volume, placental thickness and texture were analyzed for abnormalities. RESULTS: Eight fetuses were diagnosed with congenital CMV infection during the study interval. Their mean gestational age at diagnosis was 25.8 weeks (range: 23-29). All fetuses had intracranial abnormalities; increased periventricular echogenicity (n = 7), ventriculomegaly (n = 5), intracranial calcifications (n = 4), intraventricular adhesions (n = 4), thalamic hyperechogenicity (n = 3), mega cisterna magna (n = 3), lissencephaly (n = 2), vermian defect (n = 2) and cerebellar cyst (n = 1). All of them had accompanying extracranial findings, including hyperechogenic bowel (n = 6), cardiomegaly (n = 3), pericardial effusion (n = 2) and hepatosplenomegaly (n = 1). Intrauterine growth retardation was detected in 3 cases. Five pregnancies were terminated, and 1 intrauterine death occurred. The remaining 2 delivered vaginally at term. One of the live-born babies suffers from tetraparesis, mental retardation and autism, and the other has mild hemiplegia. CONCLUSIONS: The spectrum of sonographic findings may vary widely in patients with congenital CMV infection in the prenatal period. CMV should be kept in mind in differential diagnosis, particularly in fetuses with intracranial sonographic findings such as ventriculomegaly, calcifications, intraventricular adhesions and increased periventricular echogenicity.

Evaluation of serum levels of interleukin-10, interleukin-11 and leukemia inhibitory factor in differentiation of eutopic and tubal ectopic pregnancies.

PURPOSE OF STUDY: To investigate whether serum levels of leukemia inhibitory factor (LIF), interleukin 10 (IL-10) and interleukin 11 (IL-11) are different in reference to the site of implantation. METHODS: Seventeen patients with laparoscopic diagnoses of tubal ectopic pregnancy (EP) and 19 patients with intrauterine pregnancy delivering healthy term neonates (IUP) were prospectively evaluated for LIF, IL-10 and IL-11 levels. The data were compared by using the Student's t-test, chi-square test, Kruskal-Wallis and the Mann-Whitney U test with Bonferroni's correction (p < 0.05) as appropriate. RESULTS: A statistically significant difference was observed in serum LIF levels between the EP and IUP groups (p = 0.002). Ranges of LIF were 15-300 and 70-1200 ng/ml for the IUP and EP groups, respectively. There were no significant differences between groups in terms of IL-10 and IL-11 levels. CONCLUSION: LIF, but not IL-10 or IL-11, levels may be increased in early tubal ectopic pregnancies when compared to normal intrauterine pregnancies.

Cranial imaging spectrum in hypertensive disease of pregnancy.

OBJECTIVE: To determine cranial imaging findings in patients with severe preeclampsia, eclampsia and HELLP syndrome and the correlation between these findings and neurological symptoms. MATERIALS AND METHODS: CT or MRI findings of 120 patients diagnosed with severe preeclampsia, eclampsia and/or HELLP syndrome between January 1998 and December 2005 are presented. RESULTS: Pathological imaging findings were observed in 28.1% (n = 32) of the severe preeclampsia group, in 43.3% (n = 30) of the HELLP group, in 51.35% (n = 27) of the eclampsia group and in 61.9% (n = 21) of the eclampsia + HELLP group and in 45% of all patients. Thirty-five patients had specific pathology defined as ischemic lesions, edema, and perivascular microhemorrhage. Infarcts were found in seven, intracranial hemorrhage in seven, hydrocephaly in two, dural sinus thrombosis in two and a pineal cyst in one patient. Specific lesions were generally located in the posterior parietal and occipital lobes. Five patients died due to intracranial hemorrhage and one patient due to septic shock. CONCLUSION: A wide imaging spectrum from the ischemic lesion to severe intracranial hemorrhage can be detected in complicated cases of hypertensive diseases of pregnancy. It is essential to perform cranial imaging in patients with symptoms and neurological deficits.

Conservative treatment of an early ectopic pregnancy in a cesarean scar with systemic methotrexate--case report.

PURPOSE OF INVESTIGATION: Pregnancy implanted in a cesarean scar is rare, and is a life-threatening condition due to high risk of uterine rupture, hemorrhage, hysterectomy, and maternal mortality. CASE REPORT: We describe a 26-year-old woman who presented with five weeks of amenorrhea and a serum hCG level of 10,440 mIU/ml. Transvaginal sonography revealed a gestational sac of 15 x 11 mm containing a yolk sac located in a previous cesarean scar. She was successfully treated conservatively with multi-dose methotrexate. No side-effects were encountered. The serum hCG levels were undetectable in 58 days. The patient had normal menstrual cycles afterwards. CONCLUSIONS: In the view of increasing cesarean rates, healthcare professionals should be aware of the possibility of a scar pregnancy and the potentially life threatening sequelae. Early diagnosis by transvaginal sonography can improve outcome and minimize the need for emergent surgery. Conservative treatment with systemic methotrexate is an effective option in selected patients.

Conservative management of a patient with endometrial carcinoma desiring fertility: how to inform?

Conservative management of patients with endometrial cancer who desire fertility is becoming widespread in certain circumstances. A 36-year-old women desiring fertility with early-stage endometroid type adenocarcinoma of the endometrium was treated with 160 mg/d megestrol acetate for six months. After confirmation of a normal endometrial biopsy she became pregnant spontaneously. Following an uneventful pregnancy a healthy baby at term was delivered by cesarean section. Definitive surgery was performed. The risks and benefits of this thereupeutic approach are discussed and informing style of the patients emphasized.

Prenatal diagnosis of diastematomyelia: presentation of eight cases and review of the literature.

OBJECTIVES: Diastematomyelia is a rare form of spinal dysraphism. We present eight cases of diastematomyelia diagnosed prenatally in our institution as well as a review of the literature in order to determine the prognosis of isolated cases of this very unusual condition. METHODS: Records of fetuses with diastematomyelia diagnosed in our institution between January 2000 and June 2005 were collected. All liveborn fetuses were examined by a pediatric neurologist. Pre- and postnatal data were analyzed. A search was then conducted using PubMed to review previously reported cases in the literature. RESULTS: Eight cases of diastematomyelia were diagnosed during the study interval. The mean (range) gestational age at diagnosis was 21 (13-25) weeks. The main sonographic findings were widening of the spinal canal in the coronal view and an additional echogenic focus in the posterior part of the spinal column in the axial view. The diagnosis of associated open spina bifida was made in one fetus with elevated levels of amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase (AF-AChE) and the pregnancy was terminated. The other seven cases of diastematomyelia had normal levels of AF-AFP and AF-AChE and were considered isolated. One pregnancy miscarried spontaneously 1 week following amniocentesis and the remaining six were delivered at term. Review of the literature revealed 14 reports involving 26 cases of prenatally diagnosed diastematomyelia. Twelve cases had normal biochemistry and/or no additional abnormalities and all had a favorable outcome. CONCLUSIONS: When diastematomyelia is not associated with other spinal anomalies, the prognosis is favorable. Prenatal diagnosis is generally made in the second trimester but sonographic signs may be recognized as early as the first trimester. Intrauterine diagnosis of diastematomyelia should facilitate appropriate management of affected cases.

Humerus length measurement in Down syndrome screening.

PURPOSE OF INVESTIGATION: To compare the predictive values of different humeral shortness assessment methods in Down syndrome screening. METHODS: 674 high-risk singleton pregnancies with a valid last menstrual period (LMP) date were studied. Nomogram and formulas were derived from a subset of the studied group. Sensitivities of fifth percentile and cut-off values of 0.9 for observed-to-expected (obs/exp) humerus length (HL) ratio according to biparietal diameter (BPD) and gestational age (GA) were compared. RESULTS: Sensitivities were 20%, 46.7% and 60% for the 5th percentile, a cut-off value of 0.9 for obs/exp HL by BPD and a cut-off value of 0.9 for obs/exp HL by GA, respectively. CONCLUSION: Using gestational age instead of BPD when calculating expected humeral length may increase the predictive role of humeral shortness in Down syndrome screening of pregnant women with valid and correct LMP.

Heart failure caused by thyrotoxicosis in pregnancy--case report.

PURPOSE OF INVESTIGATION: To emphasize the importance of untreated thyrotoxicosis in pregnancy. When left untreated, severe maternal, fetal and even neonatal adverse outcomes such as preeclampsia, premature labor, low birthweight infants and increased perinatal mortality are prone to complicate the pregnancy. PRESENTATION: A case of thyrotoxicosis untreated during pregnancy is reported. CONCLUSION: Many authors have concluded that there is no need for routine assessment of the thyroid hormones and TSH levels in pregnancy. Nonetheless laboratory assessment for thyrotoxicosis should be done in cases with suspicious symptoms and signs. All thyrotoxic women should also be under treatment during pregnancy. Early diagnosis and/or control of hyperthyroidism would decrease the incidence of complications during pregnancy.