Maria Paola Bonasoni

Prune-Belly Syndrome: Case Series and Review of the Literature Regarding Early Prenatal Diagnosis, Epidemiology, Genetic Factors, Treatment, and Prognosis

Prune-belly syndrome (PBS) is a rare congenital syndrome characterized by deficient abdominal muscles, urinary tract malformation, and in males, cryptorchidism and has an estimated incidence of 1 in 35,000 to 1 in 50,000 live births. The syndrome might be due to severe bladder outlet obstruction or to abdominal muscle deficiency secondary to a migrational defect of the lateral mesoblast between weeks 6 and 7 of pregnancy. The current review of the medical record reports a special focus on epidemiology, genetic factors, early prenatal diagnosis clusters, treatment, and prognosis of PBS.

Predicting outcome in 259 fetuses with agenesis of ductus venosus – a multicenter experience and systematic review of the literature*

Abstract Objective: To evaluate prenatal predictors of postnatal survival in fetuses with agenesis of ductus venosus (ADV). Methods: This retrospective study reviewed our experience and the literature between 1991 and 2015. Prenatal findings were evaluated and perinatal morbidity and mortality was documented. Results: A total of 259 cases were included in the present analysis from our centers and 49 published studies (15 patients from our retrospective cohort review and 244 from literature review). The intrahepatic and extrahepatic shunts were present in 32.0% (73/226) and 67.7% (153/226), respectively. Cardiomegaly (n = 64/259, 24.7%), hydrops (n = 31/259, 12.0%) and amniotic fluid abnormalities (n = 22/259, 8.5%) were among the most frequent initial ultrasound findings. One hundred and forty-seven fetuses (56.8%) had ADV without structural anomalies while 112 (43.2%) had associated anomalies (cardiac anomalies (n = 66), extra-cardiac anomalies (n = 19) and both cardiac and extra-cardiac anomalies (n = 27)). The mean gestational age (GA) at ultrasound diagnosis was 22.9 ± 6.9 weeks while the mean GA at delivery was 34 ± 7.5 weeks. The overall neonatal survival was 57.1% (n = 148/259). The following factors were associated with survival: advanced maternal age, earlier GA at diagnosis, prematurity, increased nuchal translucency, pericardial effusion, associated cardiac defects (especially AVSD), chromosomal abnormalities, hydrops, hygroma and limb anomalies. Conclusion: Fetal hydrops, the presence of associated congenital anomalies and premature delivery are associated with poor prognosis in fetuses with ADV.

Prenatal ultrasound and histological diagnosis of fetal nasal glioma (heterotopic central nervous system tissue): report of a new case and review of the literature

IntroductionNasal glioma is a rare, benign congenital midline facial lesion.Materials and methodsPrenatal ultrasound diagnosis performed at 2nd trimester of pregnancy revealed a right-sided mass at the level of the fetal face extending from the right internal canthus to the nasal bridge.ConclusionDifferential diagnosis of facial mass in the fetus represents a critical issue because is essential in guiding the prenatal counselling of the couple and in guiding the prenatal and/or postnatal management. Alternative diagnoses such as dacryocystocele, dermoid cyst, retinoblastoma or teratoma, hemangioma, and encephalocele that can not completely be excluded prenatally are discussed. Embryology, pathology, prenatal ultrasound diagnostic clusters of the lesion as well as MR imaging findings are discussed together with review of the literature.

Prenatal diagnosis of OEIS (omphalocele, bladder exstrophy, imperforate anus, clubfeet) variant associated with increased nuchal translucency and OEIS complex with ambiguous genitalia associated with corrected transposition of the great arteries: case series and review of the literature

IntroductionThe OEIS complex refers to a combination of defects consisting in omphalocele, bladder exstrophy, imperforate anus and spinal defects and represents a rare nosologic entity (from 1:200,000 to 1:400,000 pregnancies). The defect probably occurs in early blastogenesis or in mesodermal migration during the primitive streak period.Materials and methodsTwo cases of OEIS complex diagnosed prenatally by ultrasound are reported. The medical record regarding differential diagnosis, associated anomalies, treatment and prognosis has also been sought and reported. ConclusionDifferential diagnosis with exstrophy-epispadias complex and/or cloacalexstrophy complex may be difficult antenatally by means of ultrasound. However, color Doppler has been proved to aid the diagnosis of bladder exstrophy by depicting the urine flow in direct communication with the abdominal cavity and has been useful in showing the course of the perivesical umbilical arteries. Prenatal 3D ultrasound with tomographic ultrasound imaging (TUI) and antenatal MR imaging might be useful adjuncts to conventional 2D scan in aiding the prenatal diagnosis of such malformation.

Acrania/encephalocele sequence (exencephaly) associated with 92,XXXX karyotype: Early prenatal diagnosis at 9+5 weeks by 3D transvaginal ultrasound and coelocentesis

A 27‐year‐old pregnant woman was diagnosed by 3D transvaginal ultrasound as carrying a fetus of 9+5 weeks gestation affected by acrania/encephalocele (exencephaly) sequence. A 2D transvaginal ultrasound‐guided aspiration of 5 mL of extra‐coelomic fluid was performed under cervical block before uterine suction. Conventional cytogenetic analysis demonstrated a 92,XXXX karyotype. Transvaginal 2D ultrasound‐guided coelocentesis for rapid karyotyping can be proposed to women who are near to miscarriage or in cases where a prenatal ultrasound diagnosis of congenital anomaly is performed at an early stage of development. Genetic analysis can be performed using traditional cytogenetic analysis or can be aided by fluorescence in situ hybridization (FISH). Coelocentesis may become an integral part of first trimester armamentarium and may be clinically useful in the understanding of the pathogenesis of early prenatally diagnosed congenital anomalies.

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities

OBJECTIVE Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. CASE REPORT The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. CONCLUSION Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy.

Acrania-Anencephaly Associated with Hypospadias. Prenatal Ultrasound and MRI Diagnosis and Molecular Folate Metabolism Pathway Analysis

Acrania may occur as a single isolated malformation or associated with extracranial defects. Hypospadias is one of the most common congenital abnormalities of the genitalia frequently missed on prenatal sonograms. Second trimester two- and three-dimensional ultrasound and MRI diagnosis with necropsy and folate metabolism pathway analysis. The mechanisms leading to closure of both neural and urethral tubes, are far from being demonstrated, and molecular studies of this very rare association are lacking although it might be based on a common genetic mechanism, leading to a disturbed development pathway at the molecular level.

Anencephaly-exencephaly sequence and congenital diaphragmatic hernia in a fetus with 46, XX karyotype: Early prenatal diagnosis, necropsy, and maternal folate pathway genetic analysis.

Neural tube defects (NTDs) are a group of serious birth defects that affect the developing nervous system and include acrania, anencephaly, and encephalocele. Acrania may manifest as a partial or complete absence of the cranial vault and of cerebral hemispheres (forebrain) with abnormal brain development. Anencephaly instead is generally defined as the congenital absence of skull, scalp, and forebrain. Acrania occurs more infrequently than anencephaly and may be diagnosed prenatally during the first trimester [1, 2]. It may occur as a single, isolated malformation or with co-existing anomalies including extracranial defects such as rachischisis, hypoplastic ears, cleft lip and palate, omphalocele, limb defects, cardiac and kidney

Prenatal Diagnosis of Lissencephaly Type 2 using Three-dimensional Ultrasound and Fetal MRI: Case Report and Review of the Literature

Lissencephaly is a genetic heterogeneous autosomal recessive disorder characterized by the classical triad: brain malformations, eye anomalies, and congenital muscular dystrophy. Prenatal diagnosis is feasible by demonstrating abnormal development of sulci and gyri. Magnetic resonance imaging (MRI) may enhance detection of developmental cortical disorders as well as ocular anomalies. We describe a case of early diagnosis of lissencephaly type 2 detected at the time of routine second trimester scan by three-dimensional ultrasound and fetal MRI. Gross pathology confirmed the accuracy of the prenatal diagnosis while histology showed the typical feature of cobblestone cortex. As the disease is associated with poor perinatal prognosis, early and accurate prenatal diagnosis is important for genetic counseling and antenatal care.

p.His165Pro: A novel SOX9 missense mutation of campomelic dysplasia

Campomelic dysplasia (CD) is a rare skeletal dysplasia caused by mutation in the SOX9 gene located on chromosome 17q24.3‐q25.1, which regulates testis and chondrocyte development. Severe bowing of the long bones was seen at second‐trimester scan. DNA analysis demonstrated a previously unreported de novo missense mutation in p.His165Pro. Ultrasound‐based, molecular biology diagnosis led to early therapeutic termination of pregnancy. Histologic examination of the femoral epyphyseal growth plate confirmed scanty proliferation zone and maturation zone with degenerated chondrocytes.