Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case.

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature.

BACKGROUND: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. METHODS: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. RESULTS: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. CONCLUSION: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.

Importance of Low Pregnancy Associated Plasma Protein-A (PAPP-A) Levels During the First Trimester as a Predicting Factor for Adverse Pregnancy Outcomes: A Prospective Cohort Study of 2636 Pregnant Women.

OBJECTIVES: The aim of this study is to investigate the predictive value of low levels of pregnancy associated plasma protein-A (PAPP-A) during the first trimester on adverse pregnancy outcomes, namely pregnancy induced hypertension (PIH), preeclampsia (PE), intrauterine growth restriction (IUGR), and fetal loss. METHODS: This is a prospective cohort study including 2636 women with singleton pregnancies that attended the Prenatal Diagnosis Unit of the First Department of Obstetrics and Gynecology of National and Kapodistrian University of Athens in "Alexandra Hospital" between 2017 and 2019 for the first trimester combined screening routine scan. The study population was divided into two groups according to their PAPP-A levels. The cut-off value of the PAPP-A level was defined as the 0.4 multiple of median (MoM) which is in correspondence with the fifth centile. The women were followed-up prospectively until delivery and the primary outcome measures were the incidence of PIH, PE, IUGR (<10th centile), and fetal loss.  Results: PAPP-A levels of ≤0.4 MoM were associated with increased maternal body mass index (BMI), increased uterine arteries pulsatility index (PI), and lower birth weight. Women with PAPP-A levels ≤0.4 MoM were more likely to develop PE (2.3% vs. 0.2%, p<0.001), PE or PIH (2.3% vs. 0.4%, p=0.003), IUGR (2.3% vs. 0.4%, p=0.003), and combined adverse outcome (25.5% vs. 1.9%, p<0.001) compared to women with PAPP-A>0.4 MoM. CONCLUSIONS: This study confirms that among women with PAPP-A levels ≤0.4 MoM in the first trimester, there are increased odds for PE or PIH, IUGR, and combined composite pregnancy outcome.

Prenatal diagnosis of Baraitser - Winter syndrome using exome sequencing: Clinical report and review of literature.

Baraitser - Winter Cerebrofrontofacial Syndrome (BWCFF) is a rare disorder characterized by facial dysmorphism and mental retardation of varying grades. The clinical phenotype of BWCFF indicates variable phenotypic expression involving various congenital malformations such as cardiac, renal and musculoskeletal abnormalities. Nevertheless, the prenatal presentation of BWCFF is rarely described, making prenatal diagnosis challenging. This report describes a prenatal diagnosis of BWCFF syndrome to date; a case of a fetus with intrauterine growth restriction, increased nuchal fold, bilateral hydronerphosis, rocker bottom foot and clubfoot detected on Anomaly Scan is outlined. Molecular karyotype failed to detect any abnormality. Assessment with Next Generation Sequencing was then performed, revealing a heterozygous de novo mutation in ACTB gene setting the diagnosis of BWCFF.