Background/Objectives: To identify distinct sonographic phenotypes of complex malformations of the fetal ventral wall. Methods: We performed a retrospective analysis of ultrasound reports from 160 fetuses diagnosed with complex ventral wall defects at a single tertiary referral center between 1997 and 2021. Agglomerative hierarchical clustering was applied to identify distinct sonographic phenotypes based on the level of the ventral wall defect and associated anomalies. Results: Ventral wall defects involved the abdominal wall in 150 cases, the thoracic wall in 42 cases, and the pelvic wall in 28 cases, either in isolation or in combination. Open neural tube defects were present in 58 fetuses (36.3%), spinal defects in 110 fetuses (68.8%), and limb anomalies in 45 fetuses (28.1%). Additional anomalies were identified in 38 fetuses (23.8%), including cardiac anomalies in 18 cases (11.3%). Amniotic bands were observed in seven cases (4.4%). Using agglomerative hierarchical clustering, five groups of fetuses with differing numbers of observations were identified (cluster 1, n = 104; cluster 2, n = 5; cluster 3, n = 30; cluster 4, n = 10; cluster 5, n = 11). The silhouette score of the clustering model was 0.3285. The most discriminative features for each cluster, expressed as feature importance values, were as follows: kyphoscoliosis for cluster 1 (0.924), pelvic wall defect for cluster 2 (0.852), ectopia cordis for cluster 3 (0.662), limb anomalies for cluster 4 (0.767), and spina bifida for cluster 5 (0.691). Conclusions: Complex malformations of the fetal ventral wall are associated with a wide spectrum of additional anomalies. Hierarchical clustering identified five distinct sonographic phenotypes of complex ventral wall defects, highlighting the heterogeneity of these conditions.

To explore potential genetic contributors across different subtypes of isolated neural tube defects (NTDs) - acrania-exencephaly-anencephaly sequence (AEAS), spinal dysraphism, and encephalocele - using exome sequencing (ES) in a prenatal cohort, with the goal of gaining insight into the molecular diversity underlying these distinct phenotypes. We retrospectively reviewed all fetuses diagnosed prenatally with isolated NTDs at Tel Aviv Sourasky Medical Center between September 2020 and July 2025. Detailed anatomical ultrasound excluded additional malformations. Chromosomal microarray (CMA) and trio-based ES were performed using standard protocols. Variant interpretation followed ACMG/AMP guidelines, integrating phenotypic concordance via Human Phenotype Ontology (HPO) terms. The cohort comprised 23 fetuses: 10 with AEAS (9 acrania, 1 exencephaly), 8 with spinal dysraphism (5 myelomeningocele, 3 meningocele), and 5 with encephalocele. Across the cohort, exome sequencing yielded pathogenic or likely pathogenic variants in 26% (6/23) of cases and a variant of uncertain significance in 4% (1/23). Detection rates varied by subtype, highest in encephalocele (60%), followed by spinal dysraphism (25%) and AEAS (20%). However, these findings reflect diagnostic associations rather than definitive causal relationships. Identified genes included PPP1R12A, ARHGAP35, PIEZO2, KIAA0586, TSC2, and CLCN7, representing diverse pathways in cytoskeletal organization, ciliary function, mechanotransduction, and mTOR signaling. Notably, recurrent PPP1R12A variants were found in 2 fetuses: one with AEAS and one with encephalocele, suggesting a shared morphogenetic pathway affecting cranial fold formation and mesenchymal remodeling. Our findings indicate that these distinct types of NTD, namely AEAS, spinal dysraphism, and encephalocele, may represent partially divergent embryologic and genetic entities rather than a single phenotypic continuum. Subtype-specific analysis revealed differing molecular patterns, emphasizing the value of trio-based ES in elucidating the etiology of isolated NTDs. Larger studies are needed to refine detection rates and expand our understanding of the genetic architecture underlying these distinct malformations.

Although national population-based birth defect prevalence estimates are unavailable for Bangladesh specifically, data extrapolated from the March Dimes Global Birth Defects Report indicate a prevalence of neural tube defects (NTDs) of 4.7 per 1,000 live births. This study aimed to determine the prevalence of NTD among infants born at a tertiary care multidisciplinary referral hospital in Bangladesh. Live born infants with NTD were prospectively enrolled in 2015-2021. Each enrolled NTD case was examined for type, location, and associated anomalies. The overall and annual prevalence rates were then calculated. A total of 10,372 newborns were enrolled; of them, 68 had NTD (incidence, 6.4 [range, 4.59-11.2] per 1,000 live births). The mean maternal age was 27.49± 4.72 years. Three-quarters of the NTD cases were detected at birth, and 94% of the mothers reported not taking periconceptional folic acid supplements. The meningomyelocele complex was the most frequent location. Two peaks in incidence were noted in 2017 and 2021 (10.28 and 11.2 per 1,000 live births, respectively). The distribution of different NTD types included meningomyelocele at 53%, encephalocele at 26.6%, meningocele at 16%, and anencephaly at 4.4%. A male predominance was noted overall except for anencephaly. The most common location was the lumbosacrum (47%). The NTD was isolated in 20.59% (14 of 68) of cases and associated with other malformations in 80% (54 of 68) of cases. The incidence of NTD was 6.4 per 1,000 live births at a leading tertiary care multidisciplinary referral center in Bangladesh. However, this figure might not reflect the incidence of NTD in the wider population.

Chiari Malformation Type III (CMIII) is a rare and severe hindbrain anomaly typically characterized by a low occipital or high cervical encephalocele containing brain tissue. Despite its traditional definition, considerable variability exists in the morphology and extent of the associated bony defect. With advances in magnetic resonance imaging (MRI), a more detailed understanding of CMIII anatomy is now possible. This systematic review aimed to categorize encephalocele patterns based on MRI findings in CMIII and assess their association with clinical outcomes. A systematic review of multiple databases was conducted to identify reported CMIII cases published between 1992 and 2022 with MRI-confirmed diagnoses and available outcome data. Inclusion criteria required detailed anatomical description, surgical management, and clinical follow-up. Anatomical classification was based on the extent of the osseous defect reported on MRI. Clinical outcomes included postnatal mortality (primary outcome), and neurological status, hydrocephalus, and need for cerebrospinal fluid diversion (secondary outcomes). Statistical analysis used Fisher's exact test. Twenty-five CMIII cases from 14 studies met inclusion criteria. Based on these cases, a classification into three types of CMIII was proposed: Type 1-isolated encephalocele in the occipital region; Type 2-encephalocele extending from the occiput (C0) to C2; and Type 3-encephalocele extending from C0 to the subaxial cervical spine. Mortality occurred in 20% of cases, being highest in Type 3 (37.5%) and absent in Type 1. Favorable neurological outcomes were most common in Type 1 (55.5%) and least in Type 3 (12.5%), showing a statistically significant association with defect type (p = 0.048). Hydrocephalus occurred in 72% of cases, most frequently in Type 3 (87.5%), though this was not statistically significant (p = 0.32). All surviving Type 3 cases required shunting. Rostrocaudal extension of the encephalocele defect in CMIII correlates with increasing mortality and worsening neurological outcomes. This MRI-based anatomical classification offers a practical framework for risk stratification, prognostication, and surgical decision-making in this rare and complex malformation.

Prenatal diagnosis of congenital anomalies is extremely important because permits monitoring, in utero treatments and delivery in a setting with the appropriate level of care. The aim of the study was to provide updated data on the prevalence, detection rate (DR) and gestational age at diagnosis of selected severe congenital malformations. Data on 11 isolated malformations (anencephaly, hydrocephaly, encephalocele, spina bifida, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, gastroschisis, omphalocele) were extracted from the population-based Registry of Congenital Anomalies of Tuscany. Prenatal DR, gestational age at discovery, rate of termination of pregnancy, prevalence per 10,000 births and prenatal DR trend over 30 years were calculated. Overall DR was83.2% (79.5-86.5%). DR of specific isolated anomaly was: 98.0% (89.4-99.9%) for anencephaly, 100% (71.5-100%) for encephalocele, 91.4% (81.0-97.1%) for spina bifida, 97.5% (86.9-99.9%) for hydrocephaly; 81.6% (71.0-89.5%) for transposition of the great arteries, 95.9% (86.0-99.5%) for hypoplastic left heart, 53.6% (41.2-65.7%) for limb reduction defects, 100% (69.2-100) for bilateral renal agenesis, 71.4% (57.8-82.7%) for diaphragmatic hernia, 100% (85.2-100%) for gastroschisis, 68% (46.5-85.1%) for omphalocele. There was an overall increase of the DR through decades for the majority of malformations. Prenatal DR has increased during the last 30 years. The DR depends on the specific type of anomaly with central nervous system anomaliesand bilateral renal agenesis having the highest values and limb defects (53.6 %) the lowest. Nevertheless, the diagnosis of severe malformations is not possible in all cases.