Romana Gerychová

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA‐binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.

P03.06: Management of medical termination of pregnancy (MToP) up until the 7th week of gestation in the Czech Republic: Poster discussion hub abstracts

OBJECTIVE In the Czech Republic (CR), it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester since June 2014, in case a woman submits a written request for it and in case the ultrasound examination confirms an intrauterine singleton prosperous pregnancy, between day 42 and 49 of gestation, crown-rump length (CRL) of the embryo 2-9 mm. The aim of the study is to analyze the management of MToP up until the 7th week of gestation in five centres in the CR. DESIGN Multicenter cohort (prospective) study. SETTING Department of Obstetrics and Gynecology, Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc; The Institute for the Care of Mother and Child, Charles University in Prague, Third faculty of Medicine; Department of Gynecology and Obstetrics, Charles University in Prague, First faculty of Medicine, General University Hospital in Prague; Department of Gynecology and Obstetrics, Charles University in Prague, First faculty of Medicine, Hospital Na Bulovce, Prague; Department of Gynecology and Obstetrics, Masaryk University, Faculty of Medicine, University Hospital Brno. METHODS In 2014-2016, a total of 1820 pregnant women requested MToP. The diagnosis of an intrauterine singleton prosperous pregnancy was set by transvaginal ultrasound, CRL 2-9 mm. MToP was carried out by combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally) within 48 hours. MToP follow up (exclusion of ongoing pregnancy) after 2-3 weeks was carried out by transvaginal ultrasound as well. RESULTS In 11.0% of women (201/1820) who requested MToP, CRL > 9 mm, unprosperous, multiple or ectopic pregnancy was diagnosed. In the remaining 1619 women MToP was carried out, but in 221 cases (13.7%) at least one additional pre-first visit was needed before the diagnosis of intrauterine singleton prosperous pregnancy CRL 2-9 mm could be established, in 19 cases (1.2%) two pre-first visits and in 5 cases (0.3%) even three. Gestational age was 42-49 days (average 47.1, median 47), the women were 14-47 years of age (average 30.7, median 30). In 20.8% of women (336/1619) MToP follow up was missed and of the remaining 1283 women, ongoing pregnancy (MToP failure) was diagnosed in 1.6% (24/1283), incomplete abortion in 6.5% (83/1283) and complete abortion in 91.9% (1179/1283). A subsequent surgical intervention was carried out in 7.1 % of women (91/1283). CONCLUSION A medical facility performing MToP in the 1st trimester should develop its own methodology in accordance with the legislation in force, Summaries of Product Characteristics, and recommendations of professional associations. The methodology should also include a method of evaluation of the result and management. The subsequent surgical intervention should only be performed in indicated cases. The main goal of MToP follow up is to exclude ongoing pregnancy (MToP failure), and the patient should be informed in detail about the risks involved and possibilities of their solution, it is necessary to obtain an informed consent.

Maternal white blood cell count cannot identify the presence of microbial invasion of the amniotic cavity or intra-amniotic inflammation in women with preterm prelabor rupture of membranes

Objective The main aim of this study was to determine the relationship between the maternal white blood cell (WBC) count at the time of hospital admission in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI). The second aim was to test WBC diagnostic indices with respect to the presence of MIAC and/or IAI. Methods Four hundred and seventy-nine women with singleton pregnancies complicated by PPROM, between February 2012 and June 2017, were included in this study. Maternal blood and amniotic fluid samples were collected at the time of admission. Maternal WBC count was assessed. Amniotic fluid interleukin-6 (IL-6) concentration was measured using a point-of-care test, and IAI was characterized by an IL-6 concentration of ≥ 745 pg/mL. MIAC was diagnosed based on a positive polymerase chain reaction result for the Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and/or for the 16S rRNA gene. Results Women with MIAC or IAI had higher WBC counts than those without (with MIAC: median, 12.8 × 109/L vs. without MIAC: median, 11.9 × 109/L; p = 0.0006; with IAI: median, 13.7 × 109/L vs. without IAI: median, 11.9 × 109/L; p < 0.0001). When the women were divided into four subgroups based on the presence of MIAC and/or IAI, the women with both MIAC and IAI had a higher WBC count than those with either IAI or MIAC alone, and those without MIAC and IAI [both MIAC and IAI: median, 14.0 × 109/L; IAI alone: 12.1 × 109/L (p = 0.03); MIAC alone: 12.1 × 109/L (p = 0.0001); and without MIAC and IAI: median, 11.8 × 109/L (p < 0.0001)]. No differences in the WBC counts were found among the women with IAI alone, MIAC alone, and without MIAC and IAI. Conclusion The women with both MIAC and IAI had a higher maternal WBC count at the time of hospital admission than the remaining women with PPROM. The maternal WBC count at the time of admission showed poor diagnostic indices for the identification of the presence of both MIAC and IAI. Maternal WBC count at the time of admission cannot serve as a non-invasive screening tool for identifying these complications in women with PPROM.

P33.10: Prenatal ultrasound symptoms of mucolipidosis II in two consecutive pregnancies

prenatal diagnostics of rare case of fetal mucopolysacharidosis type II according ultrasound symptoms is feaseable

P33.12: Prenatal ultrasound diagnosis of craniosynostosis with volume contrast imaging (VCI-C)

Prenatal diagnostics of fetal craniosynostosis using volume contrast imaging. Advanced ultrasound technique VCI-C making diagnostic more accurate

OP12.06: Diagnosis of placenta accreta—comparing ultrasound and MRI techniques

placental heterogeneity, placental myometrium interface, bladder wall margin, abnormal uterine bulging and parametrial invasion. The final diagnosis was made by the radiologist after considering all characteristics. Electronic charts including placental and uterine pathology reports were evaluated. Women for which delivery data was unavailable were excluded. Results: 94 women underwent fetal MRI. Delivery data was unavailable for 30 patients. The remaining 64 patients had a mean age of 34.3 years at time of MRI examination and a mean of 2 previous deliveries. 59 women (92.2%) had a history of at least one cesarean delivery, and 47 (73.4%) had placenta previa. The mean gestational age at MRI exam was 30 1/7 weeks. 23 (35.9%) women had a pathologically confirmed diagnosis of placenta accreta (including accreta, increta and percreta). MRI had a sensitivity of 91.3%, specificity of 68.3%, positive predictive value (PPV) of 61.8% and a negative predictive value (NPV) of 93.3% (Table 1). Conclusions: MRI offers an effective method for prenatal diagnosis of placenta accreta with high sensitivity and negative predictive value.

P26.05: Delayed interval to delivery in the second twin after IVF—a case report

in echogenicity between placental parts. At 34 weeks C-section was performed. Boy A (donor) 1750 g, AS 9/9, Hb 7.7, Ht 0.40, required blood transfusion. Boy B (recipient) 2100 g, AS 9/9. Hb 15.4, Ht 0.71. Examination of the placenta showed marked differences in maturation of placental parts with hydropic villi in area of twin A. There was a single AV-anastomosis from A to B. Conclusion: The sonographic finding of an echogenic placental part at the donor side is indicative of TAPS. We suggest this finding must lead to a high index of suspicion of TAPS, warrants intensified fetal monitoring and consideration of delivery as soon as fetal lung maturity is confirmed.

P16.14: Early diagnosis of diastrophic dysplasia

Diastrophic dysplasia (DTD) is characterized by limb shortening, spinal deformities, joint contractures, normal-sized skull and typical hitchhiker thumbs. It is autosomally recessive disease can be prenatally diagnosed by ultrasound and confirmed by molecular genetic testing. Most of the affected individuals have significant physical limitations and require surgical corrections. Neonates may experience respiratory insufficiency with a need of mechanical ventilation. We present a case of a twin pregnancy with one affected fetus with diastrophic dysplasia which was prenatally diagnosed in the 1st trimester. 32 year old II gravida I para referred for 1st trimester screening. Her previous pregnancy was terminated at 22wks due to diastrophic dysplasia of the fetus diagnosed during 2nd trimester ultrasound screening. This pregnancy was after IVF, dizygotic dichorionic twins. 1st trimester ultrasound (at 12wks+4 days) showed no abnormalities of the fetus A. Fetus B had symmetric upper limb shortening, limited motion range, typical hitchhiker thumbs were recognized. Diagnose of DTD of fetus B was confirmed by chorionic villus sampling (CVS), fetus A had a normal karyotype. Patient decided for a selective fetocide of the affected fetus. Fetocide of the fetus with DTD was performed at 13wks+3days. Patient went on with her pregnancy which was uncomplicated afterwards. She delivered at term a healthy neonate with no signs of skeletal dysplasia. Diagnosis of diastrophic dysplasia can be made in the 1st trimester especially in case of a previous family history of a skeletal dysplasia. Typical hitchhiker thumbs help to distinguish between other types of similar conditions.