The rare 13q33-q34 microdeletions: eight new patients and review of the literature.

The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed. Local database search yielded eight new patients with 13q33.1-q34 microdeletions (three of which had additional copy number variants). Combined with 15 cases detected by literature search, an additional 23 cases were reported in DECIPHER database, and 17 cases from ClinVar, so overall 60 patients with isolated 13q33.1-q34 microdeletions were described. Developmental delay and/or intellectual disability were noted in the vast majority of affected individuals (81.7% = 49/60). Of the 23 deletions involving the 13q34 cytoband only, in 3 cases, developmental delay and/or intellectual disability was not reported. Interestingly, in two of these cases (66.7%), the deletions did not involve the terminal CHAMP1 gene, as opposed to 3/20 (15%) of patients with 13q34 deletions and neurocognitive disability. Facial dysmorphism and microcephaly were reported in about half of the overall cases, convulsions were noted in one-fifth of the patients, while heart anomalies, short stature and hypotonia each involved about 10-30% of the cases. None of the 13q33-q34 deletions were inherited from a reported healthy parent. 13q33-q34 microdeletions are rare chromosomal aberrations, associated with high risk for neurodevelopmental disability. The rarity of this chromosomal aberration necessitates continuous reporting and collection of available evidence, to improve the ability to provide accurate genetic counseling, especially in the context of prenatal setting.

"Onion skin" sign in an ovarian mucinous cyst.

The sonographic "onion skin" sign was initially described as concentric echogenic layers in mucinous tumors unrelated to the female reproductive system. Typically, the sonographic appearance of ovarian mucinous cystadenoma includes numerous septa and fine, gravity-dependent echoes. We present a case of the "onion skin" sign in a mucinous ovarian tumor.

Invasive genetic diagnosis in multiple pregnancies.

Chromosomal anomalies and mendelian diseases are more frequent in multiple gestations than in singletons. Prenatal diagnosis is recommended in multiple pregnancies whenever indicated. Invasive testing using amniocentesis or chorionic villus sampling can be performed safely. Chorionic villus sampling has a significant advantage over amniocentesis because it offers rapid karyotyping and biochemical and DNA studies at an early stage of pregnancy. Only experienced centers should perform these procedures because of the technical aspects and the expertise needed in handling discordant results.

Head pushing versus reverse breech extraction in cases of impacted fetal head during Cesarean section.

OBJECTIVE: To compare maternal and neonatal morbidity associated with two methods to extract the impacted fetal head during Cesarean delivery. STUDY DESIGN: We retrospectively analyzed cases with difficult extraction of the impacted fetal head during Cesarean section. We compared maternal and neonatal outcomes between cases that were delivered by head extraction following pushing through the vagina ('push' method) and those that were delivered by the reverse breech technique ('pull' method). RESULTS: We reviewed 3105 Cesarean section reports. Difficult extraction necessitating the 'push' or 'pull' methods was noted in 48 (1.5%) instances. Women that were delivered by the 'pull' method had significantly lower rate of postpartum fever (5% versus 46%; odds ratios, 0.06; 95% confidence intervals, 0.007-0.51) and extensions of the uterine incision (15% versus 50%; odds ratio, 0.17; 95% CI, 0.04-0.74) compared to those that were delivered by the 'push' method. Neonatal outcomes were good in all cases. CONCLUSIONS: In cases with difficult extraction of the impacted fetal head during Cesarean section, 'pull' method may result in lower maternal morbidity compared to the traditional 'push' method.

High prevalence of müllerian anomalies diagnosed by ultrasound in women with polycystic ovaries.

OBJECTIVE: To determine, with a case-control study, if polycystic ovaries are associated with a higher rate of uterine müllerian anomalies. STUDY DESIGN: A total of 214 women were included. Transvaginal ultrasonography of the ovaries and the uterus was performed in all. The women were divided into 2 groups, a group with polycystic ovaries (n = 120) and another with normal ones (n = 94). RESULTS: Women with polycystic ovaries had a higher rate of uterine müllerian anomalies. In the polycystic ovary group, 53 (44.2%) had uterine müllerian anomalies; 17 (18.1%) were found in the normal ovary group (P < .0001). CONCLUSION: There is an association between polycystic ovaries and high rate of uterine müllerian anomalies.

Improving the diagnostic accuracy of ultrasonography in suspected acute appendicitis by the combined transabdominal and transvaginal approach.

Transabdominal ultrasound has a lower diagnostic yield in acute appendicitis than computed tomography (CT) scanning. The addition of transvaginal sonography in women with suspected appendicitis has shown improvement in the efficacy of diagnosis, potentially providing the option of selective CT use and reducing overall investigative cost and surgical delay. Two hundred ninety-two women who underwent combined transabdominal and transvaginal ultrasound for suspected acute appendicitis were evaluated. Patients were divided into two groups; Group 1 including patients with a positive sonographic diagnosis of appendicitis who underwent operation and Group 2 including patients with a negative sonographic diagnosis. Of the 157 women in Group 1, the diagnosis of appendicitis was histologically confirmed in 144 patients with five cases having a normal appendix in whom eight other pathologies were found. Of the 135 women with negative ultrasound examinations, 14 underwent surgery in which four cases of appendicitis were found. The sensitivity of the combined approach was 97.3 per cent, the specificity 91 per cent, the positive predictive value 91.7 per cent, and the negative predictive value 97 per cent. Combined ultrasound has a high predictive value for the diagnosis of appendicitis and may assist in reduction of the use of CT scanning for diagnosis and in the negative appendectomy rate.

High cytomegalovirus IgG avidity is a reliable indicator of past infection in patients with positive IgM detected during the first trimester of pregnancy.

OBJECTIVE: To evaluate the accuracy of high cytomegalovirus (CMV) specific IgG avidity in excluding recent infection in patients with anti-CMV IgM antibodies detected during the first trimester, using amniotic fluid obtained by standard amniocentesis. METHODS: Records of all patients with a positive anti-CMV IgM with IgG avidity >65% detected during pregnancy were reviewed. Amniocentesis for CMV assessment was offered to all patients. The presence of the virus in amniotic fluid was determined by polymerase chain reaction (PCR) and shell vial testing. RESULTS: Seventy-nine patients with a positive CMV IgM-high IgG avidity combination were identified. The serological tests were performed during the first trimester in 65 (82.3%) patients, of which 28 consented and underwent amniocentesis. All amniotic fluid samples were negative for CMV-PCR and CMV shell vial testing. CONCLUSIONS: IgG avidity above 65% is a good indicator of past infection, and thus excludes CMV in the amniotic fluid. In such circumstances, invasive prenatal diagnosis may eventually not be required. This optimistic conclusion, however, needs to be confirmed by large scale studies.

Variable echogenicity as a sonographic sign in the preoperative diagnosis of ovarian mucinous tumors.

OBJECTIVE: The purpose of this study was to evaluate the reliability of the "variable echogenicity" sign in the preoperative sonographic diagnosis of ovarian mucinous tumors. METHODS: Variable echogenicity was detected sonographically in different compartments of 8 adnexal multilocular masses. This finding was correlated with the final histologic results. RESULTS: All 8 tumors were mucinous cyst adenomas. In 3 of them, borderline malignancy was present. CONCLUSIONS: The sonographic detection of variable echogenicity in the contents of an adnexal multilocular cyst strongly suggests a mucinous tumor.

Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000.

The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth--138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices--sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999--were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected--r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

The onion skin sign: a specific sonographic marker of appendiceal mucocele.

OBJECTIVE: To evaluate the association of the onion skin sign as a sonographic marker for appendiceal mucocele. METHODS: The sonographic onion skin sign was considered specific for the preoperative diagnosis of appendiceal mucocele. Therefore, detection of this sign in a mass located in the right lower abdomen, unrelated to the female reproductive organs, indicated surgical intervention with a presumptive diagnosis of appendiceal mucocele. From 1998 through 2001, female patients who were found to have atypical cysts containing this sign underwent surgery. The cases were closely followed, and intraoperative findings and final histologic diagnoses were recorded. RESULTS: Appendiceal mucocele was the final diagnosis in all 7 patients in whom the onion skin sign was observed. One additional patient had an appendiceal mucocele with a sonographic picture of a clear tubular cystic structure. CONCLUSIONS: A sonographically layered cystic mass in the right lower quadrant of the abdomen in the presence of a normal ovary strongly suggests the diagnosis of appendiceal mucocele. Recognition of the sonographic onion skin sign in a cystic mass in the right lower quadrant may facilitate the accurate preoperative diagnosis of appendiceal mucocele.

Lateral distribution of ovarian dermoid cyst.

STUDY OBJECTIVE: To determine the distribution of ovarian dermoid cysts in a large series of women. DESIGN: Observational study (Canadian Task Force classification II-3). SETTING: University teaching hospitals. PATIENTS: Three hundred thirty-six women. INTERVENTION: Evaluation of operative reports. MEASUREMENTS AND MAIN RESULTS: Dermoid cysts had a mean diameter of 5.6 cm. They were present in the right ovary (48.8 %), left ovary (37.8%), and bilaterally (13.4%). Unilateral cysts were more frequent in the right ovary (56.4%) than in the left (p = 0.002, odds ratio 1.7, confidence interval 1.2-2.3). This was significantly different from the expected 50% (4.45, chi2). A similar predisposition was found when we included women with bilateral cysts (p < 0.01, OR 1.5, CI 1.1-1.9). Patient age and size of cyst did not differ between those with left and right lesions. CONCLUSION: In this large cohort of women, ovarian dermoid cysts had a predisposition to a right lateral location.

Prenatal diagnosis of Down syndrome: ten year experience in the Israeli population.

Second trimester maternal serum biochemical markers, introduced between 1990 and 1995, were supplemented with new ultrasound methods at 14-16 weeks and first trimester biochemical markers between 1995 and 2000. This study evaluated the effectiveness of a Down syndrome (DS) prevention program among the Israeli Jewish population between 1990 and 2000. We collected data on the total number of prenatal tests performed on Israeli Jewish women, DS cases detected prenatally and DS livebirths in Israel during these years. We also studied the use of the newer screening tests in 1990, 1992, and 2000. Between 1990 and 1995, use of chromosomal studies for DS in this population increased from 11.3% to 21.6% and the percentage of cases detected prenatally from 53% to 70%. However, between 1996 and 2000, even with the new screening methods, the utilization rate remained similar (20.7% and 19.8%, respectively) and the percentage detected prenatally decreased to 61% in 2000. The total cost per case detected increased from $47,971 US dollars in 1990 to $75,229 US dollars in 1992, and to $190,171 US dollars in 2000. Between 1990 and 1995, improvement in the percentage of cases detected prenatally was associated with a significant increase in the amniocentesis rate-both are attributed to the introduction of second trimester maternal serum biochemical marker tests. Unexpectedly, the introduction between 1995 and 2000 of new genetic methods to assess the DS risk did not improve the percentage detected or reduce the amniocentesis rate, and was accompanied by an increased cost per case detected.