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In this explorative study it should be evaluated how the introduction of non invasive first trimester diagnosis (nuchal translucency measurement, Combined Test, first trimester ultrasound screening) has influenced the indications and cytogenetic results of chorion villi samplings.Between 1989 and 2008 3337 pregnancies with CVS between 11 and 14 weeks of gestation were examined retrospectively. They were divided in two groups: CVS 1989 - 2001 before introduction of non invasive first trimester diagnosis (n = 1698) and CVS 2002 - 2008 after introducing non invasive testing at the end of 2001 (n = 1639). In both groups the indications for CVS (maternal age, sonographic findings, past history, maternal anxiety, and abnormal results of the Combined Test only in the second group) and the cytogenetic results were evaluated.In the first group (1989 - 2001, n = 1698) 85,6% (n = 1454) of all CVS were performed because of maternal age and only 3% (n = 51) due to sonographic findings. In the second group (2002 - 2008, n = 1639) there was a distinct increase of sonographic findings leading to CVS (33,9%, n = 555) with a clear decrease of maternal age to 37,9% (n = 621). Abnormal cytogenetic results were found in 10,5% (n = 172) in the second group, in the first group only in 4,5% (n = 76), respectively. The parameter with the highest rate of chromosomal disorders was fetal hydrops (66,1%), follwed by hygroma colli (48,2%), malformations (12,9%) and increased nuchal translucency (11,2%). Regarding maternal age alone the rate of abnormal chromosomes was 3,1%.It could be shown that non invasive first trimester diagnosis has lead to a more specific indication for invasive fetal testing (sonographic findings 33,9 vs. 3%, maternal age 37,9 vs. 85,6%) with a higher rate of chromosomal disorder in this group (10,5 vs. 4,5%).

Background and aims Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members. Methods Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene. Results Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs. Conclusion This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers.

A case of prenatal diagnosis of de novo mosaic deletion of the long arm of chromosome 13 (del(13)(q13.3)) is presented. Routine scanning in a 27-year-old primigravida at 25 weeks' gestation showed fetal bilateral hydronephrosis. Detailed anomaly scanning in our tertiary referral center further demonstrated posterior meningoencephalocele, sloping forehead, microcephaly, syndactyly and hypoplastic thumbs. Both genetic amniocentesis and cordocentesis revealed a mosaic karyotype, 46,XY/46,XY,del(13)(q13.3). Sonographic findings were confirmed by postmortem autopsy and additional abnormalities such as agenesis of corpus callosum, hypoplastic cerebellum and macroglossia were diagnosed. Detailed sonography in this case thus revealed multiple malformations that prompted fetal karyotyping at 25 weeks' gestation.

In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN) alpha-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2-90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n = 19) and untreated (n = 58) patients were 51 months (95% confidence interval [CI], 30-72) and 77 months (95% CI, 43-111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n = 6), PHR (n = 34), and less than PHR (n = 35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-alpha treatment identifies patients with a favorable long-term prognosis.

At the ob/gy department of the Innsbruck University routine, genetic amniocentesis has been offered from the 13/14 week of gestation since 1991. In 1991 44.5% of all amniocenteses were performed as early amniocentesis, it rose in 1992 to 61.5%, the rest being performed in the 16th week of gestation. In a total of 346 genetic amniocenteses, 8 pathological karyotypes were obtained (six trisomies, one 47 XXY, one marker chromosome), six from samples obtained at early amniocentesis and two obtained at the 16th week. Three weeks following the procedure, a spontaneous abortion rate of 0.87% occurred. Cultivation took 1-2 days longer with samples from early amniocentesis than with samples collected at the 16th week. In two cases the cultures failed and a repeat procedure had to be performed at the 16th week. With early amniocentesis performed at week 13/14 results are known of gestation. The long period of anxiety, which many women see as a serious disadvantage of amniocentesis is thus significantly reduced.

We present two patients, a 12 year old Turkish and a 7 year old Italian girl, with severe mental retardation, multiple congenital malformations and a constitutional interstitial deletion of the short arm of chromosome 17, del(17) (11.2). The main clinical features of this syndrome which is also referred to as the Smith-Magenis syndrome consist of a broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, hoarse deep voice and peripheral neuropathy. Behavioural abnormalities include hypermotility, self mutilation and sleep disturbances. The remarkable consistency of the main clinical features of the 59 patients documented so far permits the clinical diagnosis of this syndrome; a fact which is of importance, since many of the reported patients--including ours--were considered normal on earlier cytogenetic studies.

In a Phase II study, 82 patients with Philadelphia chromosome(Ph)-positive chronic myelogenous leukaemia were treated with 3.5 million I.U./d of recombinant interferon alpha-2c (rIFN). 73 patients have so far been evaluated (42 male, 31 female, mean age 50 [12-87] years). At the start of therapy, 10 were in the accelerated phase (group 1) and 63 in the chronic phase, of whom 19 had received previous treatment with cytotoxics (group 2), while the remainder (group 3, n = 44) had received primary treatment with rIFN. There was short-term stabilization in 7 of the 10 group 1 patients, but none had complete haematological or cytogenetic remission. In contrast, the remission rate (complete or partial haematological remission) was 63% in the previously treated (group 2) and 66% in the previously untreated chronic phase patients (group 3). There was a reduction in the proportion of Ph-positive metaphases in 7 group 2 patients (11%) and in 10 group 3 patients (23%). Complete cytogenetic remission has so far been seen in 2 patients. Cytogenetic improvement occurred after 3 months at the earliest, and in some patients only after 12 to 19 months treatment. Differences in response to treatment were related to stage (prognostic staging system of Kantarjian et al.) in group 3 patients: complete or partial haematological remission was seen in 22 out of 25 patients with stage 1 disease, in 4 out of 7 in stage 2, and in only 3 out of 12 in stages 3 and 4.