Prenatal diagnosis of a large de novo terminal deletion of chromosome 11q.

OBJECTIVE: To describe the prenatal phenotype of the 11q deletion syndrome (Jacobsen syndrome) and present the molecular characterization of the deletion in the case presented. CASE: Ultrasound at 18 and 20 weeks of gestation, on a 34-year-old woman who presented for amniocentesis, revealed slow movements, oligohydramnios and dilatation of the cerebral ventricles in the fetus. Maternal and paternal ages were 34 and 38 years, respectively. RESULTS: Prenatal karyotyping of cultured amniotic fluid cells revealed an 11q terminal deletion, 46,XX,del(11)(q23) (Jacobsen syndrome). Real-time quantitative PCR analysis was used to identify and map the breakpoint physically to a 45-kb region located 14.5 Mb from the 11q telomere. Polymorphic DNA marker analysis showed that DNA sequences on the paternally derived chromosome are deleted. At autopsy, facial dysmorphism without major malformations was recorded. Examination of the internal organs disclosed the following abnormalities: a Meckels' diverticulum of 4-mm length, adhesion between the gall bladder and the transverse colon, and bilaterally bilobed lungs without further situs anomalies. CONCLUSION: Our case demonstrates significant phenotypic variability of Jacobsen syndrome at midtrimester pregnancy; the syndrome may be manifested at this stage only by mild to moderate ventriculomegaly of the brain.

Introital ultrasound of the lower genital tract before and after colposuspension: a 4-year objective follow-up.

OBJECTIVE: To assess the topography of the bladder neck by introital ultrasound before and after open colposuspension. METHODS: Three hundred and ten women with urodynamically proven stress urinary incontinence were included in this long-term study to investigate the position and function of the bladder neck at rest and during straining. Height (H), distance (D), and urethrovesical angle of the bladder neck (beta) were measured by means of preoperative and postoperative introital ultrasound. Women were followed up; 152 of them (49%) completed 48 months of follow-up. RESULTS: At the 6-month follow-up examination, 90.0% of the women were continent (279/310), 3.5% (11/310) showed voiding difficulties, 3.5% (11/310) had urgency, and 1.6% (5/310) had developed de novo urge incontinence. At the 48-month follow-up, 76.8% of the patients were still continent. All postoperative measurements yielded significantly lower values for angle beta at rest and during straining compared with the preoperative results (P < 0.0001). The median linear movement of the bladder neck during straining decreased from 18.0 mm before surgery to 6.4 mm at the 48-month follow-up (P < 0.0001). The median level of ventrocranial elevation of the vesicourethral junction was 14.3 mm immediately after surgery, 9.9 mm after 6 months and 6.6 mm after 48 months. The degree of surgical bladder-neck elevation was associated with postoperative urgency/de novo urge incontinence (P < 0.0001) and voiding difficulty (P < 0.0001). CONCLUSIONS: The colposuspension procedure reduces angle beta at rest and during straining, restricts linear movement with straining, and elevates the bladder neck. Perioperative introital ultrasound improves understanding of this surgical procedure and might help to prevent postoperative complications.

[Ultrasound imaging of the lower urinary tract in women before and after colposuspension: a 6-month follow-up]. / Introitussonographie des unteren Genitaltraktes vor und nach Kolposuspension: eine sechsmonatige Nachbeobachtung.

OBJECTIVE: To evaluate the position of the bladder neck before and after open Burch colposuspension, using introital ultrasound. DESIGN: Retrospective longitudinal study using pre- and post-operative sonographic assessment of the position and function of the bladder neck. SETTING: Urogynecology units at the universities of Marburg/Göttingen and Witten/Herdecke and the DRK district hospital in Alzey, Germany. PATIENTS: 310 women undergoing open Burch colposuspension for primary genuine stress incontinence between September 1992 and December 2001. METHOD: Two-dimensional introitus sonography of the bladder neck prior to, one week and six months after surgery. RESULTS: The median age at surgery was 55 years (26 - 85). Open colposuspension lead to a 90.0 % (279/310) cure rate at 6 months with only 3.5 % (11/310) of the patients showing persistent micturation problems. A further 11.6 % (36/310) had symptoms of urgency and in 7 patients (2.3 %) a de novo urge-incontinence occurred. Post-operative bladder neck angles and movements at rest and during valsalva manoeuvre were significantly reduced while the resting bladder neck position was significantly elevated (p < 0.0001). Anatomical elevation of the bladder neck after open colposuspension varied between 2 - 39 with a median of 14.3 mm of neck elevation after one week and 9.9 mm at 6 month, respectively. Incontinence surgery lead to a significant reduction of the urethral funneling (p < 0.0001). CONCLUSION: In our series, open Burch colposuspension decreased both the bladder neck angle and the linear movement at rest and on valsalva as a result of the surgically stabilized bladder neck. Thus, our results support the hammock hypothesis that even small changes in the position of neck position are sufficient to reverse incontinence. We believe that perioperative introitus sonography is a helpful tool for the clinical assessment and documentation of not only morphological but also functional changes of the female continence organ before and after open Burch colposuspension.

Uterine cervical metastasis of breast cancer: a rare complication that may be overlooked.

BACKGROUND: Metastasis of distant malignancies to the cervix uteri is a rare occurrence and the frequency is approximately 4% for all tumours. However, the frequency of cervical metastasis of breast cancer is much lower and is estimated to range between 0.8 and 1.7%. With the exception of ovarian metastases, secondary tumours of the female genital tract are rather uncommon. Therefore, these conditions pose diagnostic problems for the clinician. PATIENT: A 40-year-old woman with the diagnosis of invasive ductal cell carcinoma of the right breast underwent mastectomy with dissection of axillary lymph nodes in 1998. Subsequently, the patient received 6 cycles of chemotherapy with cyclophosphamide, methotrexate and fluorouracil. The initial tumour stage was pT2, pN0 (0/13), M0, G2. The oestrogen and progesterone receptors were positive and expression of the C-erb-B2 coding oncogene was negative. Gynaecological and ultrasonographic examination revealed a normal cervix without evident lesions. Exfoliative cytology was negative. 14 months after treatment the patient presented with an axillary relapse and surgery, second-line chemotherapy with doxorubicine and radiation therapy of the chest wall and the axilla were performed. The patient developed liver metastases 14 months later and at this time ultrasonographic pelvic examination revealed a 2.2 cm tumour of the cervix with good vascularisation. The patient had no clinical symptoms, i.e. no vaginal bleeding or discharge. Sonomorphologically this tumour appeared as a leiomyoma of the cervix. Cervical biopsies and curettage, however, revealed metastatic carcinoma expressing oestrogen and progesterone receptors consistent with the primary breast cancer. Under palliative chemotherapy with docetaxel progression of liver metastases and cervical metastasis occurred and the patient died 9 months later. CONCLUSION: Metastatic involvement of the cervix should be considered in women with a history of breast cancer who present with vaginal bleeding or suspicious changes of the cervix on transvaginal ultrasound. Therefore, gynaecological and ultrasonographic examination of the pelvis represent an important part of the follow- up investigations in women with primary breast cancer.

[Diagnosis and therapy of uterine sarcoma]. / Diagnostik und Therapie der Uterussarkome.

Radical surgery in stage I and II uterine sarcoma removing all tumor manifestations is the only curative therapy option for early stage disease. Larger tumors (> 4 cm) and the presence of lymph node metastasis correlate with a high local recurrence rate. For these tumors adjuvant radiation and/or adjuvant chemotherapy may be recommended after surgical therapy. Adjuvant therapy however, should preferably be considered for uterine stromal sarcomas and mixed mesodermal tumors. The toxicity of radiation and/or chemotherapy is greater than any possible benefit for patients with leiomysarcomas as these tumors rarely respond to radiation or chemotherapy. For advanced (> stage I and II) and recurrent disease, curative therapy options are not available and palliative therapy for these patients has to take into consideration the negative side effects and weigh up quality of life against an often very limited possible benefit of such therapy.

Homozygous factor V Leiden mutation in a woman with multiple adverse pregnancy outcomes.

We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy.

[Interphase FISH test as a rapid test for trisomies in amniotic fluid--results of a prospective study]. / Interphase-FISH-Test als Schnelltest für Trisomien im Fruchtwasser--Ergebnisse einer prospektiven Untersuchung.

BACKGROUND: Specific DNA probes allow rapid prenatal diagnosis of numerical chromosome disorders (chromosomes 13, 18, 21, X, Y) by FISH on interphase nuclei. The diagnostic reliability is presently under evaluation. STUDY GROUP: In a period of 1.5 years a total 1126 amniotic fluid samples was investigated by FISH compared to standard cytogenetic analysis. RESULTS: The success rate was 93 percent (< or = 30 nuclei) and 84% (< or = 50 nuclei). An abnormal karyotype was detected by FISH in 27 of 28 successfully hybridised samples, including trisomy 21 [16], trisomy 13 [4], trisomy 18 [4], aberrations of sex chromosomes [4]. Two cases with clinically relevant cytogenetic abnormalities were in principle not detectable by FISH. One false-negative finding was observed, possibly arising from maternal cell contamination of the sample. 6% of all samples, respectively 23% of the bloody samples were contaminated by maternal cells (more than 10%). CONCLUSION: Maternal contamination represents the most important limitation of the diagnostic reliability in routine practice.

Paternal origin of trisomy 21 following intracytoplasmic sperm injection (ICSI).

One important aspect in the debate on the genetic risks associated with intracytoplasmic sperm injection (ICSI) is the possible increased rate of chromosomal abnormalities in resulting pregnancies. ICSI was performed in a 27 year old man with asthenoteratozoospermia and his 25 year old wife. There was a spontaneous miscarriage at 9 weeks of gestation. Cytogenetic investigation revealed trisomy 21. Analysis of two polymorphic microsatellite markers showed that the additional chromosome was paternal. This is in contrast to the fact that the vast majority of trisomic concepti are maternal in origin. Identifying the parent of origin in trisomic conceptions achieved by ICSI may reveal whether ICSI is associated with an increased risk of paternally derived aneuploidy.

Relevance of genetic counselling in couples prior to intracytoplasmic sperm injection.

Since the first reports of successful pregnancies after treatment with intracytoplasmic sperm injection (ICSI) in humans numerous attempts have been made to assess the genetic risks of this highly invasive technique. During the study period (February 1995-November 96), 142 couples were referred to our genetic counselling unit prior to ICSI. In three couples, genetic counselling revealed a high recurrence risk for a monogenic disease (myotonic dystrophy, hereditary ataxia and polycystic kidney disease). In nine out of 128 men (7%) an abnormal karyotype was identified, including three Robertsonian translocations, two reciprocal translocations, three sex chromosome aberrations and one case with centric fission of chromosome no. 7. A total of 14 men refused chromosomal analysis. Only one of the 122 women examined had an abnormal karyotype (47, XXX). Five out of six men with congenital bilateral absence of the vas deferens (CBAVD) had at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Three had mutations in both CFTR alleles, including one case in which the second mutation was the 5T allele. One patient with CBAVD and a single Delta F508 CFTR mutation also had left renal agenesis. In conclusion, we strongly recommend that genetic counselling, chromosomal analysis and, in the case of CBAVD, screening for CFTR mutations should be offered to all couples with a diagnosis of male or idiopathic infertility.