Prenatal characterization of novel neurosonographic findings in a fetus with SOTOS syndrome.

Sotos syndrome is a rare genetic disorder that occurs in less than 1 in 10,000 births. It is characterized by rapid growth during childhood (tall stature and unusually large head), typical facial dysmorphic features, neurodevelopmental delays of both mental and movement abilities, and learning disabilities. Prenatal diagnosis of Sotos syndrome is infrequent and sonographic findings are not well characterized as the condition is generally detected during childhood. We present a case in which routine third trimester ultrasound detected intracranial findings including ventriculomegaly, periventricular pseudocysts, and increased periventricular echogenicity. Although initially suspected to be the result of fetal infection with CMV, amniocentesis excluded fetal infection and microarray analysis detected a de novo 2.13 MB interstitial deletion of 5q35.2-35.3 involving several genes including the NSD1 gene, thus confirming the diagnosis of Sotos syndrome. This case provides novel characterization of the sonographic phenotype in a fetus with Sotos syndrome and discusses the differential diagnosis.

A de novo pathogenic variant in DHX30 gene in a fetus with isolated dysgenesis of the corpus callosum.

A 36 years old woman in her first pregnancy was referred at 24w3d for a dedicated neurosonographic examination due to a suspected short corpus callosum (CC). The examination depicted a dysgenetic CC with asymmetric thickness at the level of the body in coronal views, very thin in the midline and thicker in both sides, suggesting bilateral formation of Probst bundles. The BPD, HC, and transverse cerebellar diameters were in the normal low range without associated growth restriction. Associated anomalies were not detected in the brain or other organs. Following genetic consultation and a normal CMA, trio exome sequencing was performed and a de novo missense pathogenic mutation c.2353 C > T in the DHX30 gene was detected. This variant has been previously reported in children and adults, mostly with a severe phenotype including neurodevelopmental disorder with variable motor and language impairment, but also mild phenotypes have been reported. MRI describes delayed myelination, ventriculomegaly, and cortical and cerebellar atrophy as imaging features in affected patients. This is the first prenatal report of a DHX30-associated neurodevelopmental disorder in which the fetus presents with isolated callosal dysgenesis, stressing the importance of exome sequencing in fetuses with this condition, as far as it is phenotypic presentation of numerous syndromes with different outcomes.

Clinical Practice Guidelines and Recommendations by the World Association of Perinatal Medicine and Perinatal Medicine Foundation: Reporting Suspected Findings from Fetal Central Nervous System Examination.

These guidelines follow the mission of the World Association of Perinatal Medicine, in collaboration with the Perinatal Medicine Foundation, which brings together groups and individuals worldwide, with the aim to improve prenatal detection of central nervous system anomalies and the appropriate referral of pregnancies with suspected fetal anomalies. In addition, this document provides further guidance for healthcare practitioners with the goal of standardizing the description of ultrasonographic abnormal findings.

Improved differentiation between hypo/hypertelorism and normal fetuses based on MRI using automatic ocular biometric measurements, ocular ratios, and machine learning multi-parametric classification.

OBJECTIVES: To differentiate hypo-/hypertelorism (abnormal) from normal fetuses using automatic biometric measurements and machine learning (ML) classification based on MRI. METHODS: MRI data of normal (n = 244) and abnormal (n = 52) fetuses of 22-40 weeks' gestational age (GA), scanned between March 2008 and June 2020 on 1.5/3T systems with various T2-weighted sequences and image resolutions, were included. A fully automatic method including deep learning and geometric algorithms was developed to measure the binocular (BOD), inter-ocular (IOD), ocular (OD) diameters, and ocular volume (OV). Two new parameters, BOD-ratio and IOD-ratio, were defined as the ratio between BOD/IOD relative to the sum of both globes' OD, respectively. Eight ML classifiers were evaluated to detect abnormalities using measured and computed parameters. RESULTS: The automatic method yielded a mean difference of BOD = 0.70 mm, IOD = 0.81 mm, OD = 1.00 mm, and a 3D-Dice score of OV = 93.7%. In normal fetuses, all four measurements increased with GA. Constant values were detected for BOD-ratio = 1.56 ± 0.05 and IOD-ratio = 0.60 ± 0.05 across all GA and when calculated from previously published reference data of both MRI and ultrasound. A random forest classifier yielded the best results on an independent test set (n = 58): AUC-ROC = 0.941 and F1-Score = 0.711 in comparison to AUC-ROC = 0.650 and F1-Score = 0.385 achieved based on the accepted criteria that define hypo/hypertelorism based on IOD (< 5th or > 95th percentiles). Using the explainable ML method, the two computed ratios were found as the most contributing parameters. CONCLUSIONS: The developed fully automatic method demonstrates high performance on varied clinical imaging data. The new BOD and IOD ratios and ML multi-parametric classifier are suggested to improve the differentiation of hypo-/hypertelorism from normal fetuses. KEY POINTS: • A fully automatic method for computing fetal ocular biometry from MRI is proposed, achieving high performance, comparable to that of an expert fetal neuro-radiologist. • Two new parameters, IOD-ratio and BOD-ratio, are proposed for routine clinical use in ultrasound and MRI. These two ratios are constant across gestational age in normal fetuses, consistent across studies, and differentiate between fetuses with and without hypo/hypertelorism. • Multi-parametric machine learning classification based on automatic measurements and the two new ratios improves the identification of fetal ocular anomalies beyond the accepted criteria (<5th or >95th IOD percentiles).

Reduced adipose tissue in growth-restricted fetuses using quantitative analysis of magnetic resonance images.

OBJECTIVES: Fat-water MRI can be used to quantify tissues' lipid content. We aimed to quantify fetal third trimester normal whole-body subcutaneous lipid deposition and explore differences between appropriate for gestational age (AGA), fetal growth restriction (FGR), and small for gestational age fetuses (SGAs). METHODS: We prospectively recruited women with FGR and SGA-complicated pregnancies and retrospectively recruited the AGA cohort (sonographic estimated fetal weight [EFW] ≥ 10th centile). FGR was defined using the accepted Delphi criteria, and fetuses with an EFW < 10th centile that did not meet the Delphi criteria were defined as SGA. Fat-water and anatomical images were acquired in 3 T MRI scanners. The entire fetal subcutaneous fat was semi-automatically segmented. Three adiposity parameters were calculated: fat signal fraction (FSF) and two novel parameters, i.e., fat-to-body volume ratio (FBVR) and estimated total lipid content (ETLC = FSF*FBVR). Normal lipid deposition with gestation and differences between groups were assessed. RESULTS: Thirty-seven AGA, 18 FGR, and 9 SGA pregnancies were included. All three adiposity parameters increased between 30 and 39 weeks (p < 0.001). All three adiposity parameters were significantly lower in FGR compared with AGA (p ≤ 0.001). Only ETLC and FSF were significantly lower in SGA compared with AGA using regression analysis (p = 0.018-0.036, respectively). Compared with SGA, FGR had a significantly lower FBVR (p = 0.011) with no significant differences in FSF and ETLC (p ≥ 0.053). CONCLUSIONS: Whole-body subcutaneous lipid accretion increased throughout the third trimester. Reduced lipid deposition is predominant in FGR and may be used to differentiate FGR from SGA, assess FGR severity, and study other malnourishment pathologies. CLINICAL RELEVANCE STATEMENT: Fetuses with growth restriction have reduced lipid deposition than appropriately developing fetuses measured using MRI. Reduced fat accretion is linked with worse outcomes and may be used for growth restriction risk stratification. KEY POINTS: • Fat-water MRI can be used to assess the fetal nutritional status quantitatively. • Lipid deposition increased throughout the third trimester in AGA fetuses. • FGR and SGA have reduced lipid deposition compared with AGA fetuses, more predominant in FGR.

The normal 14-18 gestational weeks "parasagittal complex" view of the fetal brain. A 3D transvaginal neurosonographic study.

OBJECTIVE: To study the early second trimester development of brain hemispheres, lateral ventricles, choroid plexus, and ganglionic eminence/basal ganglia complex (GEBG). METHODS: A retrospective analysis of TVUS 3D volumes of 14-18 gestational weeks (GW) fetuses. Hemispheres were analyzed for wall thickness, choroid plexus extension, GEBG height and length, lamination pattern (intermediate zone and the subplate border, IZ-SP), ventricle height, width, and angle. Measurements were correlated with GW and assessed for symmetry and impact of probe resolution. RESULTS: We included 84 fetuses (168 hemispheres). The CP location is variable at 14-16 GW, becoming consistently and symmetrically posterior at 18 GW. Hemispheric thickness, GEBG height and length grow significantly with fetal age, whereas ventricle height, width, and angle regress. The detection rate of the IZ-SP line at 14, 15, 16, 17, and 18 weeks was 0%, 24%, 78.26%, 100%, and 100%, respectively. The ratio between the upper and lower segments of the cerebral lamination grows with GW. For all brain structures, the asymmetry between sides was significant only for ventricular height. The transducer type did not have a significant effect on any outcome except for ventricle height. CONCLUSION: These normal features of the parasagittal view should aid clinicians in fetal brain assessment during the early weeks of the second trimester.

SMARCC1 is a susceptibility gene for congenital hydrocephalus with an autosomal dominant inheritance mode and incomplete penetrance.

A Jewish couple of mixed origin was referred for genetic counseling following termination of pregnancy at 18 weeks of gestation due to severe ventriculomegaly with aqueduct stenosis. Trio exome sequencing revealed a loss-of-function heterozygous variant in the SMARCC1 gene inherited from an unaffected mother. The SMARCC1 gene is associated with embryonic neurodevelopmental processes. Recent studies have linked perturbations of the gene with autosomal dominant congenital hydrocephalus, albeit with reduced penetrance. However, these studies were not referenced in the SMARCC1 OMIM record (*601732) and the gene was not considered, at the time, an OMIM morbid gene. Following our case and appeal, SMARCC1 is now considered a susceptibility gene for hydrocephalus. This allowed us to reclassify the variant as likely pathogenic and empowered the couple to make informed reproductive choices.

Myocardial Function in Fetuses with Congenital Cytomegalovirus Infection.

INTRODUCTION: The objective of this study was to investigate myocardial deformation of left (LV) and right ventricle (RV) using 2-dimensional speckle-tracking echocardiography (2D-STE) in fetuses with and without congenital cytomegalovirus (CMV) infection. METHODS: This was a prospective single-center study. Vertical transmission was defined by a positive CMV polymerase chain reaction (PCR) test on the amniotic fluid or on the neonate's urine. Fetuses were divided into group 1 and group 2 if CMV-PCR was positive or negative, respectively. LV and RV global longitudinal strain (GLS) values were obtained and adjusted for gestational age by calculating Z-scores. Univariate analysis was carried out to compare cardiac indices between group 1 and group 2. RESULTS: Fetuses from group 1 (n = 11) had a significantly lower LV myocardial shortening than those from group 2 (n = 32). GLS was -20.7 ± 5.2% and -26.3 ± 4.1%, respectively (p = 0.001). Similarly, GLS Z-score was lower (0.02 ± 0.72) in group 1 than in group 2 (-0.80 ± 0.59) (p = 0.001). Similarly, RV GLS Z-score was significantly impaired in group 1 compared to group 2 (-0.44 ± 1.03 vs. -1.04 ± 0.71, p = 0.041). CONCLUSION: Fetuses with congenital CMV showed subclinical biventricular myocardial dysfunction. Further studies are needed to confirm the potential role of 2D-STE in identifying fetuses with congenital CMV at risk of postnatal cardiovascular morbidities.

Monogenic Causes of Apparently Idiopathic Perinatal Intracranial Hemorrhage.

OBJECTIVE: Perinatal intracranial hemorrhage (pICH) is a rare event that occurs during the fetal/neonatal period with potentially devastating neurological outcome. However, the etiology of pICH is frequently hard to depict. We investigated the role of rare genetic variations in unexplained cases of pICH. METHODS: We performed whole-exome sequencing (WES) in fetuses and term neonates with otherwise unexplained pICH and their parents. Variant causality was determined according to the American College of Medical Genetics and Genomics (ACMG) criteria, consistency between suggested genes and phenotypes, and mode of inheritance. RESULTS: Twenty-six probands (25 families) were included in the study (9 with a prenatal diagnosis and 17 with a postnatal diagnosis). Intraventricular hemorrhage (IVH) was the most common type of hemorrhage (n = 16, 62%), followed by subpial (n = 4, 15%), subdural (n = 4, 15%), and parenchymal (n = 2, 8%) hemorrhage. Causative/likely causative variants were found in 4 subjects from 3 of the 25 families (12%) involving genes related to the brain microenvironment (COL4A1, COL4A2, and TREX-1). Additionally, potentially causative variants were detected in genes related to coagulation (GP1BA, F11, Von Willebrand factor [VWF], FGA, and F7; n = 4, 16%). A potential candidate gene for phenotypic expansion related to microtubular function (DNAH5) was identified in 1 case (4%). Fifty-five percent of the variants were inherited from an asymptomatic parent. Overall, these findings showed a monogenic cause for pICH in 12% to 32% of the families. INTERPRETATION: Our findings reveal a clinically significant diagnostic yield of WES in apparently idiopathic pICH and support the use of WES in the evaluation of these cases. ANN NEUROL 2021;89:813-822.

Fetal cerebral ventriculomegaly: What do we tell the prospective parents?

Fetal cerebral ventriculomegaly is a relatively common finding, observed during approximately 1% of obstetric ultrasounds. In the second and third trimester, mild (≥10 mm) and severe ventriculomegaly (≥15 mm) are defined according to the measurement of distal lateral ventricles that is included in the routine sonographic examination of central nervous system. A detailed neurosonography and anatomy ultrasound should be performed to detect other associated anomalies in the central nervous system and in other systems, respectively. Fetal MRI might be useful when neurosonography is unavailable or suboptimal. The risk of chromosomal and non-chromosomal genetic disorders associated with ventriculomegaly is high, therefore invasive genetic testing, including microarray, is recommended. Screening for prenatal infections, in particular cytomegalovirus and toxoplasmosis, should also be carried out at diagnosis. The prognosis is determined by the severity of ventriculomegaly and/or by the presence of co-existing abnormalities. Fetal ventriculoamniotic shunting in progressive isolated severe ventriculomegaly is an experimental procedure. After delivery, ventricular-peritoneal shunting or ventriculostomy are the two available options to treat hydrocephalus in specific conditions with similar long-term outcomes. A multidisciplinary fetal neurology team, including perinatologists, geneticists, pediatric neurologists, neuroradiologists and neurosurgeons, can provide parents with the most thorough prenatal counseling. This review outlines the latest evidence on diagnosis and management of pregnancies complicated by fetal cerebral ventriculomegaly.

Upgrading an intronic TMEM67 variant of unknown significance to likely pathogenic through RNA studies and community data sharing.

FETAL PHENOTYPE: A couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14 + 2 weeks of gestation following a previous pregnancy termination due to posterior encephalocele and enlarged kidneys. The index pregnancy was also positive for several fetal abnormalities, including enlarged kidneys with cystic dysplasia and abnormal cerebellar morphology highly suggestive of Joubert syndrome. GENETIC DIAGNOSTIC TEST PERFORMED, RESULT, AND INTERPRETATION: Trio exome sequencing revealed compound heterozygosity for variants in the TMEM67 gene: a known pathogenic maternally inherited variant found in trans with a paternal intronic variant of unknown significance. RNA analysis revealed that the intronic variant creates a cryptic acceptor splice site in intron 12, leading to the insertion of 22 bp and causing a frameshift with a premature stop codon. This analysis enabled the reclassification of the intronic variant to likely pathogenic. IMPLICATIONS AND NOVELTY: This information empowered the couple to make informed reproductive choices and opt for preimplantation genetic testing (PGT) for future pregnancies.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

A New BCl6 Transcriptional Corepressor Variant Mosaicism in a Fetus with Severe Fetal-Eye Anomalies.

We present the prenatal imaging of a fetus with severe eye anomalies diagnosed as carrying a new variant mosaicism on the BCOR gene.

A unique brain germinal matrix involvement in cytomegalovirus infected fetuses: A retrospective neurosonographic analysis with outcome correlation.

OBJECTIVE: To study the clinical significance of brain germinal matrix (GM) changes in cytomegalovirus (CMV) infected fetuses. METHOD: This is a retrospective analysis. Group A; isolated GM finding, with or without lenticulostriatal vasculopathy (LSV). Group B; non-isolated lesion. Amniocentesis, urinalysis, postnatal US and developmental assessment, were obtained. RESULTS: Group A and B included 18 and four fetuses, respectively. In group A, mean fetal age at diagnosis was 34.3 weeks (31-38 weeks). In 15/18 (83.3%), the lesion was bilateral and LSV was present in 8/18 (44.4%). Small cysts appeared inside the lesion in 5/18 (27.7%). MRI was normal in 8/18 (44.4%). Subtle or inconclusive findings were reported in the remaining fetuses. Brain ultrasound was normal in 10/18 (55.5%) of newborns. In the remaining, caudothalamic cyst with or without LSV, or isolated LSV were found. All newborns are developing normally at a mean follow-up age of 33.3 months (+/- 19.6 moths). In group B, all four patients requested for termination of pregnancy. CONCLUSION: Fetal CMV infection may cause focal GM changes, frequently accompanied by LSV, late in pregnancy. These changes may be isolated, or as part of a more generalized brain damage. When isolated, favorable prognosis is expected.

Neurodevelopmental outcome of children born with an isolated atretic cephalocele.

PURPOSE: The existing data on the neurodevelopmental outcome of children born with an isolated atretic cephalocele (IAC) are scant. We aimed to expand upon these data by describing our experience with affected children, as well as assist parents and clinicians in deciding how to proceed when an IAC is diagnosed prenatally. METHODS: A follow-up study was conducted on nine children who were born with an IAC. Evaluations were performed by pediatric neurologists and child development specialists. Developmental outcomes were based on a global development evaluation that assessed gross and fine motor skills, receptive and expressive language levels, activities of daily living, communication skills, and social domains. Adaptive skills were estimated by the Adaptive Behavior Assessment System, Second Edition. RESULTS: None of the nine children (median age 4 years and 6 months) had abnormal findings on neurological examination. Six children had age-appropriate developmental milestones, two had a mild motor delay, and one had mild expressive language delay (catchup was achieved by all of the latter three by ~ 3.5 years of age). The mean general adaptive composite score was 105 ± 11.7 (normal = 100). None of the children had behavioral, social, or communication problems. CONCLUSIONS: Children diagnosed with an IAC with/without a falcine sinus and devoid of coexisting intracranial abnormalities seem to have a normal neurodevelopmental outcome. Continuation of pregnancy may be recommended when an IAC is detected prenatally, and reassurance if detected postnatally.

Prenatal Diagnosis of Snijders Blok-Campeau Syndrome in a Fetus with Macrocephaly.

We present the prenatal imaging and whole exomics sequencing with the newly described Snijders Blok-Campeau macrocephaly syndrome.

The early pattern of human corpus callosum development: A transvaginal 3D neurosonographic study.

OBJECTIVE: To provide an in-vivo description of early corpus callosum (CC) development. METHODS: We reviewed 3D US volumes acquired transvaginally (TVUS) through the anterior fontanelle, between 14 to 17 weeks. The following landmarks were recognized: tela-choroidea (TC), foramina of Moro, early CC and the evolving cavum septi pellucidi. The following measurements were taken: total, anterior and posterior sections, and height of the CC (referenced to the anterior TC border). All measurements were correlated to both the gestational age and the transverse cerebellar diameter (TCD). RESULTS: Eighty nine volumes were included in the study (mean 15.1 weeks ± 0.84, TCD range, 13.1-18.4 mm) with high inter and intra observer correlation of the measurements. We found high correlation between CC length and height, and TCD. The anterior segment of the CC appear earlier than the posterior one, and growth continues bi-directionally. Initially, the posterior elongation is significantly larger than the anterior one. Association of all CC measurements with TCD remained significant when co-varying for maternal age and fetal sex. CONCLUSIONS: imaging the fetal CC is feasible from 14 weeks by TVUS, by following the suggested insonation approach. The early CC develops bi-directionally, and the posterior elongation is more significant than the anterior one.

Agenesis of the septum pellucidum: Prenatal diagnosis and outcome.

OBJECTIVE: The purpose of this study is to describe the imaging findings in a group of fetuses with suspected agenesis of the septum pellucidum (ASP) and to evaluate their clinical outcome. METHODS: This is a retrospective multicenter study on a cohort of fetuses diagnosed with suspected ASP, between 2008 and 2017. The records of each patient, including ultrasound (US) and magnetic resonance studies, were reviewed and compared with the postnatal findings. RESULTS: Forty-seven patients were included in the study at a mean gestational age of 26.6 weeks. In 17 patients, the ASP was considered isolated. Fourteen patients delivered live-born, and all 14 are developing normally. Three were lost to follow-up. Twenty-four patients had associated malformations involving the central nervous system (CNS); 13 were delivered (normal development [5], abnormal [6] and no follow-up [2]). Nine patients opted for termination, and two pregnancies were lost to follow-up. Six patients had non-CNS associated findings, two were delivered with normal neurological development and four had a termination. CONCLUSIONS: Isolated ASP is usually associated with a favorable outcome; but in the presence of associated malformations, there is at least a 50% risk of abnormal development. Current imaging techniques can provide an accurate prognosis in cases when ASP appears isolated.

Periventricular pseudocysts of noninfectious origin: Prenatal associated findings and prognostic factors.

OBJECTIVE: The purpose of this study was to establish prognostic factors in fetuses diagnosed with periventricular pseudocysts (PVPCs) without known congenital infection, between 28 and 37 weeks of gestation. METHODS: This retrospective study included cases of fetal PVPC from 2008 to 2018. PVPCs were classified according to location, number, extension, morphology, and size. Additional findings, MRI and genetic studies were recorded. Pregnancy outcome, postnatal, or postmortem results were obtained. Images from patients with normal (Group 1) and abnormal postnatal development (Group 2) were compared for analysis of factors predictive of outcome. RESULTS: One-hundred and fifteen pseudocysts were observed in 59 patients. In 34 fetuses (57%), the PVPC was an isolated finding. Thirty-nine patients delivered live newborns, 27% opted for termination of pregnancy, and 4 patients were lost to follow-up. Eighty-four percent of the liveborns had normal development. When assessing for the influence of pseudocyst characteristics, a wide CSP, or large head circumference, neither of these affected the outcome. The presence of additional anomalies was the only positive predictor for abnormal development regradless of specific PVPC characteristics (P = .002). CONCLUSIONS: In fetuses with PVPCs, the presence of additional anomalies was the only predictor for adverse postnatal outcome. No association between cystic characteristics and adverse outcome was observed.

Obstetric and perinatal outcomes in cases of congenital Zika syndrome.

OBJECTIVE: To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS). METHODS: A dual prospective and retrospective cohort study involving 102 pairs of mothers and fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS). RESULTS: Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed. CONCLUSION: Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones.