Prenatal diagnosis in estimating the prognosis of sacrococcygeal teratoma.

: Sacrococcygeal teratoma is a rare congenital malformation, the prognosis depends on factors affecting foetal development. The diagnosis is based on ultrasound examination, especially the evaluation of the detailed morphology of the foetus in the 20th week of pregnancy. Therefore, it is crucial to keep looking for ultrasound markers that would prenatally determine the most accurate prognosis for the foetus. Now, we rely on a small number of studies with a predominance of case reports. We offer a literature review of the essential information concerning sacrococcygeal teratoma diagnostics, therapy, and complications of sacrococcygeal teratomas in connection with prenatal diagnosis. It turns out that in cases with a favourable prognosis according to prenatal ultrasound examination and adequate surgical treatment after childbirth, the prognosis of this congenital malformation is excellent.

Cushings syndrome in pregnancy caused by an adrenal adenoma.

OBJECTIVE: The description of a rare case of Cushings syndrome caused by an adrenal adenoma in pregnancy with successful treatment. CASE PRESENTATION: 30-ear-old Gravida 3 female was admitted to our hospital with hypertension at the 18th week of gestation. Hormonal analyses revealed primary Cushings syndrome with high plasma cortisol levels and low levels of adrenocorticotropic hormone. Magnetic resonance imaging demonstrated a mass on the right-side of the adrenal gland. Adrenalectomy was performed in the 28th week of gestation and the following histopathology revealed an adrenocortical adenoma. Pregnancy continued until the 38th week of gestation with glucocorticoid replacement therapy and the patient gave birth vaginally to a healthy boy in the 38th week of gestation. CONCLUSION: Cushings syndrome in pregnancy rarely occurs; dia-gnosis may be dismissed or determined after birth in most cases. Misdia-gnosis of Cushings syndrome is common because of physiological increase of corticotropin hormones and cortisol levels and overlapping symptoms that can occur even during physiological pregnancy. Cushings syndrome should have a place in the differential dia-gnosis of hypertension in pregnancy (especially before the 20th week of gestation). Analysis of the urinary free cortisol level and circadian rhythm blood cortisol can provide a reasonable strategy to dia-gnose Cushings syndrome in pregnant women. Early dia-gnosis and surgical treatment can significantly reduce maternal and fetal complications.

Cervical Gardnerella vaginalis in women with preterm prelabor rupture of membranes.

OBJECTIVE: To determine the association between microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and the cervical prevalence of Gardnerella vaginalis DNA in pregnancies with preterm prelabor rupture of membrane (PPROM). METHOD: In total, 405 women with singleton pregnancies complicated with PPROM were included. Cervical fluid and amniotic fluid samples were collected at the time of admission. Bacterial and G. vaginalis DNA were assessed in the cervical fluid samples using quantitative PCR technique. Concentrations of interleukin-6 and MIAC were evaluated in the amniotic fluid samples. Loads of G. vaginalis DNA ≥ 1% of the total cervical bacterial DNA were used to define the cervical prevalence of G. vaginalis as abundant. Based on the MIAC and IAI, women were categorized into four groups: with intra-amniotic infection (both MIAC and IAI), with sterile IAI (IAI without MIAC), with MIAC without IAI, and without either MIAC or IAI. RESULTS: The presence of the abundant cervical G. vaginalis was related to MIAC (with: 65% vs. without: 44%; p = 0.0004) but not IAI (with: 52% vs. without: 48%; p = 0.70). Women with MIAC without IAI had the highest load of the cervical G. vaginalis DNA (median 2.0 × 104 copies DNA/mL) and the highest presence of abundant cervical G. vaginalis (73%). CONCLUSIONS: In women with PPROM, the presence of cervical G. vaginalis was associated with MIAC, mainly without the concurrent presence of IAI.

Association of rare non-coding SNVs in the lung-specific FOXF1 enhancer with a mitigation of the lethal ACDMPV phenotype.

Haploinsufficiency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. In one case, the deletion of the maternal allele of the FOXF1 enhancer caused pulmonary hypertension and histopathologically diagnosed MPV without the typical ACD features. In the second case, the deletion of the paternal enhancer resulted in ACDMPV rather than the expected neonatal lethality. In both cases, FOXF1 expression in lung tissue was higher than usually seen or expected in patients with similar deletions, suggesting an increased activity of the remaining allele of the enhancer. Sequencing of these alleles revealed two rare SNVs, rs150502618-A and rs79301423-T, mapping to the partially overlapping binding sites for TFAP2s and CTCF in the core region of the enhancer. Moreover, in a family with three histopathologically-diagnosed ACDMPV siblings whose missense FOXF1 mutation was inherited from the healthy non-mosaic carrier mother, we have identified a rare SNV rs28571077-A within 2-kb of the above-mentioned non-coding SNVs in the FOXF1 enhancer in the mother, that was absent in the affected newborns and 13 unrelated ACDMPV patients with CNV deletions of this genomic region. Based on the low population frequencies of these three variants, their absence in ACDMPV patients, the results of reporter assay, RNAi and EMSA experiments, and in silico predictions, we propose that the described SNVs might have acted on FOXF1 enhancer as hypermorphs.

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.