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bnormalities in different regions of Iran, most of which were conducted on live births. This study was conducted to determine fetal abnormalities in pregnancies leading to legal abortion in Golestan province. Methods: This descriptive-analytical study was conducted on 199 pregnant women with a gestational age of less than 20 weeks with abortion licenses from the Forensic Medicine Center of Golestan province over 9 months during 2018-19. Demographic characteristics, including parents’ age, ethnicity, and family relationship, and the type of fetal abnormalities were recorded. Results: Given 29,460 births in Golestan province over a 9-month period, the prevalence of fetal abnormalities was determined to be 6.75 per thousand births. The incidence rates of fetal abnormalities were determined to be 6.78, 6.68, 7.69, and 5.65 per thousand births in native Fars (80 cases), Turkmen (65 cases), Sistani (34 cases), and other (20 cases) ethnic groups, respectively. Since the gender of 80 fetuses was unknown, the incidence rates of abnormality were determined to be 4.36 and 3.72 per thousand births in female (63 cases) and male (56 cases) fetuses, respectively. The most common fetal abnormalities included central nervous system (n=49, 24.62%), chromosomal abnormalities (n=47, 23.61%), and cardiovascular impairments (n=26, 13.06%). The incidence of fetal abnormalities was not found to have a statistically significant relationship with parents' age, ethnicity, and family relationship. Conclusion: The most prevalent fetal abnormality was related to central nervous system disorders. The incidence of fetal abnormalities had no relationship with the parents’ age, ethnicity, and family relationship. [ABSTRACT FROM AUTHOR]

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case with a prenatal diagnosis of AGS. The first fetal ultrasound detected bilateral lateral ventricle cystic structures, and fetal MRI was performed to identify other signs. The right parietal lobe signal showed cerebral white matter abnormalities, and fetal brain development level was lower than that of normal fetuses of the same gestational age. Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site, and the final comprehensive diagnosis was AGS1. In this article, we also reviewed the previous literature for possible phenotypes in the fetus and found that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS. [ABSTRACT FROM AUTHOR]

This study aimed to analyze, in the São Paulo state of Brazil, time trends in prevalence, neonatal mortality, and neonatal lethality of central nervous system congenital malformations (CNS-CM) between 2004 and 2015. Population-based study of all live births with gestational age ≥22 weeks and/or birthweight ≥400 g from mothers living in São Paulo State, during 2004–2015. CNS-CM was defined by the presence of International Classification Disease 10th edition codes Q00–Q07 in the death and/or live birth certificates. CNS-CM was classified as isolated (only Q00–Q07 codes), and non-isolated (with congenital anomalies codes nonrelated to CNS-CM). CNS-CM associated neonatal death was defined as death between 0 and 27 days after birth in infants with CNS-CM. CNS-CM prevalence, neonatal mortality, and lethality rates were calculated, and their annual trends were analyzed by Prais-Winsten Model. The annual percent change (APC) with 95% confidence interval (95%CI) was obtained. 7,237,628 live births were included in the study and CNS-CM were reported in 7526 (0.1%). CNS-CM associated neonatal deaths occurred in 2935 (39.0%). Isolated CNS-CM and non-isolated CNS-CM were found respectively in 5475 and 2051 livebirths, with 1525 (28%) and 1410 (69%) neonatal deaths. CNS-CM prevalence and neonatal lethality were stationary, however neonatal mortality decreased (APC −1.66; 95%CI −3.09 to −0.21) during the study. For isolated CNS-CM, prevalence, neonatal mortality, and lethality decreased over the period. For non-isolated CNS-CM, the prevalence increased, neonatal mortality was stationary, and lethality decreased during the period. The median time of CNS-CM associated neonatal deaths was 18 h after birth. During a 12-year period in São Paulo State, Brazil, neonatal mortality of infants with CNS-CM in general and with isolated CNS-CM showed a decreasing pattern. Nevertheless CNS-CM mortality remained elevated, mostly in the first day after birth. [ABSTRACT FROM AUTHOR]

This paper discusses the clinical value of standardized early pregnancy ultrasound structure screening in the diagnosis of fetal central nervous system (CNS) malformations. In this paper, 6902 cases (8336 fetuses) of 11～13 + 6 weeks of gestation (5468 cases of singleton pregnancy and 1434 cases of twin pregnancy) underwent standardized early pregnancy ultrasound structure screening. While tracking the pregnancy process and clinical outcome, we found that 13 cases of CNS malformations (10 cases of single pregnancy, 3 cases of twin pregnancy) were detected by prenatal ultrasound in 6902 cases (8336 fetuses) 11～13 + 6 weeks of gestation including 5 cases of exposed brain malformations. There were 4 cases of children with cerebral sickle disease, 2 cases of forebrain without splitting, 1 case of meningocele, and 1 case of open spina bifida. There were 4 cases with other structural abnormalities and 3 cases with abnormal karyotype. Follow-up results of 13 fetuses indicated that except for 3 cases of twin malformed fetuses who continued to be pregnant after selective reduction, ultrasound results of the remaining fetuses were consistent with autopsy results after the induction of labor. For this reason, it can be concluded that standardized ultrasound structural screening during early pregnancy can detect fetal CNS malformations early and has important clinical value in reducing the birth rate of malformed fetuses and guiding obstetric treatment. [ABSTRACT FROM AUTHOR]

Objective: Holoprosencephaly (HPE, #MIM 236100) is the most common developmental defect of midline cleavage in the human forebrain. Environmental, genetic, and multifactorial causes are involved in its etiology. About half of the cases have chromosome aberrations such as trisomies 13 and 18, triploidy and structural imbalances. Single gene mutations have been shown in ~25% of cases. In this retrospective study, we aimed to determine the etiological factors related to HPE in 127 fetuses. Material and Method: This study comprises 127 prenatally diagnosed fetal HPE samples from a period of 25 years, which were evaluated by karyotyping, fluorescence in situ hybridization (FISH) and aCGH investigation. Results: A total of 64 (50.39%) chromosome aberrations were identified in this cohort. The predominant chromosomal abnormality was trisomy 13 (n=38), which was followed by trisomy 18 (n=8) and triploidy (n=5). Terminal 7q deletion was the most frequent structural anomaly (n=10, of which 5 were de novo deletion, 4 were an unbalanced product of maternal translocations and one unknown in origin) and the deletion of 18p was detected in one case. In the remaining two cases, we detected trisomy 20 and pericentric inversion 11 coincidentally. Conclusion: This study, indicates that in the presence of clinical findings suggesting HPE, cytogenetic and molecular cytogenetic studies should be performed. An aCGH study must also be done for submicroscopic chromosomal anomalies, to determine their sizes, real breakpoints and identify possible novel genes that might play a role in HPE etiology. [ABSTRACT FROM AUTHOR]

Objective: To analyze the venous anatomy of the dural sinuses of patients with posterior encephaloceles, in order to formulate anatomical patterns which can ensure safer surgery. Methods: This is a retrospective study, analyzing eight patients diagnosed with posterior encephalocele throughout 1 year. Results: Eight patients with cephaloceles were evaluated in our study from January 2017 to January 2018. The most common alteration was dysgenesis of the straight sinus (n = 7), followed by venous anomalies in the encephalocele and alterations in the SSS (superior sagittal sinus) (n = 4), and the occurrence of a falcine sinus (FC) in 3 patients. Conclusion: Anatomical variations are frequent in patients with cephaloceles. Therefore, an understanding of them is necessary for safe and effective treatment. [ABSTRACT FROM AUTHOR]

Tubulinopathy commonly refers to complex congenital and non-progressive brain malformations caused by mutations in the tubulin genes. Among tubulin-encoding genes, TUBB3 has rarely been reported as a cause of complex cortical malformations. Herein, we report a case of tubulinopathy in a 21-month-old boy who presented with delayed development. He could not walk on his own and was not able to speak more than five words. Physical examination revealed right esotropia and hypotonia of the lower extremities. MRI showed dysmorphic brainstem and dysmorphic and hypertrophic basal ganglia. The right thalamus was relatively smaller than the left one. The cerebellum showed disorganization of the cerebellar folia. DNA sequencing revealed a missense mutation of the TUBB3 gene. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities are responsible for several congenital malformations in the world, some of these are associated to telomeric/subtelomeric deletions. The abnormalities involving the telomere of chromosome 12 are rare, with few reports of deletions involving 12q24.31 region in the literature, and, to our knowledge, only four of them in the 12q24.31-q24.33 region. We report a further case of interstitial deletion of bands 12q24.31-q24.33 associated with autism spectrum disorder. A 2-year-old boy with global developmental delay associated with multiple congenital anomalies. The Human Genome CGH Microarray 60K confirmed the diagnosis of 12q deletion syndrome. This study made a review of the current literature comparing our patient with previously reported cases. These detailed analyses contribute to the development of genotype/phenotype correlations for 12q deletions that will aid in better diagnosis and prognosis of this deletion. [ABSTRACT FROM AUTHOR]

Objectives: To describe the spectrum of brainstem malformations associated to mutations in the tubulin genes taking advantage of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).Methods: Fifteen patients (six males; median age, 1.25 years; range, 1 month to 31 years) with mutations in the tubulin genes (TUBA1A = 8, TUBB2B = 4, TUBB3 = 3) studied with MRI and DTI were included in the study. Brain MR exams were reviewed to describe the malformative aspects of the brainstem. Malformations of the supratentorial brain and cerebellum were also recorded. Tractography was performed in seven selected cases.Results: Fourteen patients (93%) showed complex malformations of the brainstem. Most common findings, apparent on anatomical MR sequences, were brainstem asymmetry (12 cases, 5 of which with a crossed pattern characterised by a hypertrophic right medulla oblongata and hypertrophic left pons), short and small pons on midline (10 cases) and anterior brainstem clefting (6 cases). DTI revealed abnormal transverse pontine fibres (13 cases), fusion of corticospinal tracts and medial lemnisci (9 cases) and a small decussation of the superior cerebellar peduncles (7 cases).Conclusions: Conventional/anatomical MRI and DTI reveal a complex pattern of brainstem malformations associated with tubulin genes mutations.Key Points: • Brainstem malformations affect 93% patients with mutated tubulin genes • MRI shows homolateral and crossed brainstem asymmetries, clefts and pons hypoplasia • DTI demonstrates irregular representation of transverse pontine fibres and fusion of corticospinal tracts. [ABSTRACT FROM AUTHOR]

Objective: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. Methods: Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. Results: Diagnosis was most often set in <1 year old (40.6%) or >12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. Conclusion: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years. [ABSTRACT FROM AUTHOR]

The Dicer1, Dcr-1 homolog (Drosophila) gene encodes a type III ribonuclease required for the canonical maturation and functioning of microRNAs (miRNAs). Subsets of miRNAs are known to regulate normal cerebellar granule cell development, in addition to the growth and progression of medulloblastoma, a neoplasm that often originates from granule cell precursors. Multiple independent studies have also demonstrated that deregulation of Sonic Hedgehog (Shh)-Patched (Ptch) signaling, through miRNAs, is causative of granule cell pathologies. In the present study, we investigated the genetic interplay between miRNA biogenesis and Shh-Ptch signaling in granule cells of the cerebellum by way of the Cre/lox recombination system in genetically engineered models of Mus musculus (mouse). We demonstrate that, although the miRNA biogenesis and Shh-Ptch-signaling pathways, respectively, regulate the opposing growth processes of cerebellar hypoplasia and hyperplasia leading to medulloblastoma, their concurrent deregulation was nonadditive and did not bring the growth phenotypes toward an expected equilibrium. Instead, mice developed either hypoplasia or medulloblastoma, but of a greater severity. Furthermore, some genotypes were bistable, whereby subsets of mice developed hypoplasia or medulloblastoma. This implies that miRNAs and Shh-Ptch signaling regulate an important developmental transition in granule cells of the cerebellum. We also conclusively show that the Dicer1 gene encodes a haploinsufficient tumor suppressor gene for Ptch1-induced medulloblastoma, with the monoallielic loss of Dicer1 more severe than biallelic loss. These findings exemplify how genetic interplay between pathways may produce nonadditive effects with a substantial and unpredictable impact on biology. Furthermore, these findings suggest that the functional dosage of Dicer1 may nonadditively influence a wide range of Shh-Ptch-dependent pathologies. [ABSTRACT FROM AUTHOR]

The treatment options for symptomatic arachnoid cysts are shunting, open craniotomy, and endoscopic fenestration. Endoscopic fenestration of large arachnoid cyst is safe and effective. Postoperative subdural hematoma and intraparenchymal hemorrhage can be avoided by endoscopic fenestration. This technique has the additional advantage of identifying and treating ventricular abnormalities, such as foramen of Monro stenosis and cerebral aqueduct occlusion. This report describes endoscopic dual fenestration in a child with large multicompartmental intraventricular arachnoid cyst extending from foramen magnum to foramen of Monro. The child presented with difficulty to hold the neck in upright position, irritability, vomiting, and large head. Follow-up postoperative magnetic resonance imaging at 3 months showed a significant reduction in size of the cyst. Clinically, the patient showed a gradual improvement at 10 months follow-up. Probably this is the first report of this nature. [ABSTRACT FROM AUTHOR]

Abstract: The authors describe the case of a six-year-old girl with Ehlers-Danlos syndrome associated to bilateral symmetrical frontal polymicrogyria. Several extracellular matrix components, including collagen, are directly implicated in the neuronal migration. We think that a defect in collagen or in another extracellular matrix protein during fetal development could result in this association. [Copyright &y& Elsevier]

Dandy-Walker malformation is characterized by complete or partial agenesis of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa with displacement of the lateral sinuses. This article aims to present current, anatomical, etiological, pathophysiological, syndromic and treatment aspects of this malformation. [ABSTRACT FROM AUTHOR]