SARS-CoV-2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series.

INTRODUCTION: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood. MATERIAL AND METHODS: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress. RESULTS: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain. CONCLUSION: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

[Neonatal death due to congenital transmesenteric hernia].

Transmesenteric hernia (TMH) is a rare cause of small bowel obstruction. If left untreated, mortality rates are high. In this case report, the authors describe a case of TMH in a preterm neonate born at gestational age 36 + 1 with abdominal distention, subumbilical discolouration and difficulty breathing at birth. The neonate died shortly post-partum due to respiratory failure. Subsequent autopsy showed TMH with small bowel obstruction, distention, and necrosis. High-standing diaphragm with small lungs was the cause of death.

Mosaicism for copy number variations in the placenta is even more difficult to interpret than mosaicism for whole chromosome aneuploidy.

OBJECTIVE: To compare mosaicisms in prenatal chorionic villus samples (CVSs) with corresponding postpartum placental samples. METHOD: We collected placentas from 15 consecutive cases of mosaicism detected in CVSs and obtained five standardized samples on each placenta after delivery. All pre- and postnatal placental samples were uncultured and analyzed by high-resolution chromosomal microarray. RESULTS: Ten cases of mosaicism for whole chromosome aneuploidy (mWC) and five cases with mosaicism for (sub)chromosomal copy number variations (mCNVs) were included. In 5/10 mWC cases and in 4/5 mCNV cases the prenatally detected aberration was confirmed in the postpartum placenta. Three postpartum placentas revealed various complex aberrations differing from the prenatal results: (1) mosaicisms for different deletions/duplications on 9p and 9q in all samples (prenatal: mosaic 5.3 Mb duplication on 9p24), (2) different regions with deletions/duplications/loss of heterozygosity on 1p in all samples (prenatal: mosaic 2.3 Mb 1p36 duplication), and (3) mosaicism for a duplication on 5q and a deletion on 6p in one out of five samples (prenatal: mosaic trisomy 7). CONCLUSION: CNVs constitute a complex subgroup in placental mosaicism. Counseling of these couples after chorionic villus sampling should not focus on the specific CNV involved, but on the nature of mosaicism and the option of amniocentesis and ultrasound.

Placental mosaicism in the era of chromosomal microarrays.

OBJECTIVE: Placental mosaicism for a subset of a chromosome, a structural chromosomal aberration, is thought to be a very rare finding in chorionic villus samples. Here, we present clinical and laboratory data on five cases with such mosaicism for structural chromosomal aberrations. METHODS: During a period of 6 months, chromosomal microarray was carried out on DNA extracted from 100 uncultured chorion villous samples from high-risk pregnancies. RESULTS: In five of 100 consecutively collected samples (5/100), mosaicism for a structural chromosomal aberration was detected. The mosaic aberration was subsequently detected in fetal tissue in three of the five cases. CONCLUSION: Chromosomal microarray can detect placental mosaicism for structural chromosomal aberrations. This kind of mosaicism may be more frequent than previously anticipated, and the fetal involvement seems difficult to predict. These findings highlight the complexity of mosaicism for structural chromosomal aberrations in prenatal samples in the chromosomal microarray era.

Mitochondrial Disease Caused by a Novel Homozygous Mutation (Gly106del) in the SCO1 Gene.

The cytochrome C oxidase assembly protein SCO1 gene encodes a mitochondrial protein essential for the mammalian energy metabolism. Only three pedigrees of SCO1mutations have thus far been reported. They all presented with lactate acidosis and encephalopathy. Two had hepatopathy and hypotonia, and the other presented with intrauterine growth retardation and hypertrophic cardiomyopathy leading to cardiac failure. Mitochondrial disease may manifest in neonates, but early diagnosis has so far been difficult. Here, we present a novel mutation in the SCO1 gene: in-frame deletion (Gly106del)with a different phenotype without encephalopathy, hepatopathy, hypotonia, or cardiac involvement. Within the first 2 h the girl developed hypoglycemia and severe chronic lactate acidosis. Because of the improved technique in whole exome sequencing, an early diagnosis was made when the girl was only 9 days old, which enabled the prediction of prognosis as well as level of treatment. She died at 1 month of age.

Phenotypic spectrum associated with SPECC1L pathogenic variants: new families and critical review of the nosology of Teebi, Opitz GBBB, and Baraitser-Winter syndromes.

The SPECC1L protein plays a role in adherens junctions involved in cell adhesion, actin cytoskeleton organization, microtubule stabilization, spindle organization and cytokinesis. It modulates PI3K-AKT signaling and controls cranial neural crest cell delamination during facial morphogenesis. SPECC1L causative variants were first identified in individuals with oblique facial clefts. Recently, causative variants in SPECC1L were reported in a pedigree reported in 1988 as atypical Opitz GBBB syndrome. Six families with SPECC1L variants have been reported thus far. We report here eight further pedigrees with SPECC1L variants, including a three-generation family, and a further individual of a previously published family. We discuss the nosology of Teebi and GBBB, and the syndromes related to SPECC1L variants. Although the phenotype of individuals with SPECC1L mutations shows overlap with Opitz syndrome in its craniofacial anomalies, the canonical laryngeal malformations and male genital anomalies are not observed. Instead, individuals with SPECCL1 variants have branchial fistulae, omphalocele, diaphragmatic hernias, and uterus didelphis. We also point to the clinical overlap of SPECC1L syndrome with mild Baraitser-Winter craniofrontofacial syndrome: they share similar dysmorphic features (wide, short nose with a large tip, cleft lip and palate, blepharoptosis, retrognathia, and craniosynostosis), although intellectual disability, neuronal migration defect, and muscular problems remain largely specific to Baraitser-Winter syndrome. In conclusion, we suggest that patients with pathogenic variants in SPECC1L should not be described as "dominant (or type 2) Opitz GBBB syndrome", and instead should be referred to as "SPECC1L syndrome" as both disorders show distinctive, non overlapping developmental anomalies beyond facial communalities.

Postpartum placental CT angiography in normal pregnancies and in those complicated by diabetes mellitus.

INTRODUCTION: Pregnancy complicated by diabetes mellitus (DM) is a central obstetric problem often complicated by fetal macrosomia and increased risk of intrapartum asphyxia. This risk might be explained by fetoplacental vascular abnormalities. This study aimed to investigate the fetoplacental vascular volume by placental CT angiography in normal pregnancies and in pregnancies complicated by type 1 DM (T1DM), diet controlled gestational DM (GDMd), and insulin treated gestational DM (GDMi). METHODS: Postpartum, barium contrast enhanced placental CT angiography was performed in 27 normal pregnancies and 25 DM pregnancies (8 T1DM, 8 GDMd, and 9 GDMi). The fetoplacental vascular volume/placenta weight (FVV/PW)-ratio and fetoplacental vascular volume/birth weight (FVV/BW)-ratio of each diabetic group were compared to the normal group with multiple regression analysis adjusted for GA. In all pregnancies a standardized histopathological placental examination was performed postpartum. RESULTS: In normal pregnancies, the fetoplacental vascular volume increased with GA (p < 0.001), placental weight (p < 0.001), and birth weight (p < 0.001). In T1DM and GDMi pregnancies, the gestational age adjusted placental weight and the birth weight were increased when compared to normal pregnancies (p < 0.05). The FVV/BW-ratio was significantly reduced in both T1DM and GDMi pregnancies when compared to normal pregnancies (p = 0.003 and p = 0.009, respectively). DISCUSSION: This study demonstrates, that in insulin treated DM pregnancies the fetus as well as the placenta is larger than normal. However, despite a large placenta, a relatively smaller fetoplacental vascular volume supplies the macrosomic fetus. This finding might explain why fetuses from insulin treated DM pregnancies have high vulnerability to intrauterine and intrapartum asphyxia.

Segmental overgrowth syndrome due to an activating PIK3CA mutation identified in affected muscle tissue by exome sequencing.

Mosaic PIK3CA-mutations have been described in an increasing number of overgrowth syndromes. We describe a patient with a previously unreported segmental overgrowth syndrome with the mutation, PIKCA3 c.3140A>G (p.His1047Arg) in affected tissue diagnosed by exome sequencing. This PIK3CA-associated segmental overgrowth syndrome overlaps with CLOVES syndrome and fibroadipose hyperplasia but is distinct from each of these entities.

A case of isolated neck extensor myopathy responding favorably to immunotherapy.

We report on a case of a 79-year-old man with dropped head syndrome, where diagnostic tests, ruling out other differential diagnoses, confirmed the relatively rarely occurring condition known as isolated neck extensor myopathy. Biopsy of the neck extensor musculature was with classical pronounced fibrosis, without signs of myositis. The patient was treated with 3 cycles of corticosteroids with pronounced clinical improvement of his symptoms. This emphasizes the importance of considering isolated neck extensor myopathy as a differential diagnosis when encountered with a patient with dropped head syndrome and the importance of trying therapy with corticosteroids even when myositis is absent.