CNS Anomalies Research Articles

P97 – 3032: Epidemiological study of neurometabolic diseases diagnosed at Cairo University Children Hospital: A two years outcome

Objective To study the prevalence of inherited metabolic disorders diagnosed at the Unit of inherited metabolic disease at Cairo University Children Hospital (CUCH), focusing on the wide variability of clinical presentations of these diseases as well as on the risk factors and demographic distribution. Methods 1289 patients were evaluated clinically at the neurometabolic unit from 2008 to 2010 with retrospective analysis of the data. Results Out of 1289 patients, 120 Patients were diagnosed as Phenylketonuria: 67 males (55.8%) and 53 females (44.2%), with age of presentation range (few days to 14 years). The remaining 1169 patients: 672 males (57.5%) with age range (1 week–18 years). Positive consanguinity was observed in 60.3% of patients. Excluding the PKU group: neurological manifestations were predominantly reported as 34.2% of clinical findings, non neurologic manifestations as 16.9%, dysmorphic/skeletal abnormalities and isolated short stature: 12.5%. Positive risk factors: 11.1%. Dermatological manifestations: 5.1%, ocular/auditory defects: 4.8%, failure to thrive: 4.7%. Metabolic disturbances: 4.3%. Organomegaly: 3.4%. CNS anomalies and neuroimaging findings: 2.7% and an asymptomatic group: 0.2%. A final diagnosis was confirmed in 782/1289 patients (60.6%) among which 288 (36.8%) were metabolic disorders: Aminoacidopathies were diagnosed in 146 patients (18.7%), lysosomal storage disorders in 78 (10%), organic acidurias in 18 (2.3%), dyslipideamias in 10 (1.3%), other leukodystrophies in 10 (1.3%), mitochondrial disorders in 9 (1.2%), carbohydrate metabolic disorders in 8 (1%), peroxisomal disorders in 6 (0.8%), metal disorders in 3 (0.4%), urea cycle disorders in 3 (0.4%) and 1 (0.1%) had a congenital disorder of glycosylation. 494 patients (63.2%) had genetic and other non metabolic diseases. Conclusion Inherited inborn errors of metabolism and genetic non metabolic disorders are not uncommon in Egyptian population due to high rate of consanguinous marriages. Therefore, we recommend initiation of a national newborn screening program or at least, a selective screening for the high risk families for early diagnosis and future prevention of disabilities caused by these disorders.

Birth weight by gestational age and congenital malformations in Northern Ethiopia.

BackgroundStudies on birth weight and congenital anomalies in sub-Saharan regions are scarce.MethodsData on child variables (gestational age, birth weight, sex, and congenital malformations) and maternal variables (gravidity, parity, antenatal care, previous abortions, maternal illness, age, medication, and malformation history) were collected for all neonates delivered at Ayder referral and Mekelle hospitals (Northern Ehthiopia) in a prospective study between 01-12-2011 and 01-05-2012.ResultsThe total number of deliveries was 1516. More female (54%) than male neonates were born. Birth weights were 700-1,000 grams between 26 and 36 weeks of pregnancy and then increased linearly to 3,500-4,000 grams at 40 weeks. Thirty-five and 54% of neonates were very-low and low birth weight, respectively, without sex difference. Very-low birth-weight prevalence was not affected by parity. Male and female neonates from parity-2 and parity-2-4 mothers, respectively, were least frequently under weight. Sixty percent of newborns to parity -3 mothers weighed less than 2,500 grams, without sex difference. The percentage male neonates dropped from ~50% in parity-1-3 mothers to ~20% in parity-6 mothers. Diagnosed congenital malformations (~2%) were 2-fold more frequent in boys than girls. The commonest malformations were in the central nervous system (CNS; ~1.5% of newborns). Parity, low birth weight, gestational age less than 35 weeks, male sex, and lack of antenatal care were the most significant risk factors for congenital anomalies.ConclusionThe high prevalence of neonates with low birth weight and CNS anomalies in Northern Ethiopia was very high. The findings may reflect the harsh conditions in the past 2 decades and suggest environmental and/or nutritional causes. Male sex and parity affected the outcome of pregnancy negatively.

Fetal Brain MRI: Novel Classification and Contribution to Sonography.

1) To evaluate and classify the indications for fetal brain MRI in a tertiary referral center. 2) To assess the contribution of fetal brain MRI to fetal neurosonography. A retrospective study in a tertiary medical center during a two-year period (2011 - 2012) included pregnant women who underwent fetal brain MRI. MRI was implemented at 32 weeks of gestation unless a severe abnormality possibly requiring earlier medical intervention was suspected. 633 patients were included, 40 (6.3%) underwent repeated examinations with a total of 733 fetal MRI scans. Patients were classified to three main indication cohorts: Suspected primary brain anomaly (52.9%), non-CNS disorders (32.5%) and obstetrical complications (14.6%). These cohorts were further divided into 16 separate groups with lateral ventricle abnormalities being the most common (23.7%), followed by exposure to TORCH (17.5%) and cerebral cortex abnormalities (13%). 149 (19.3%) fetal MRI scans demonstrated additional findings. Repeated examinations were commonly implemented in complicated monochorionic-biamniotic (MCBA) twin pregnancies (34.6%) and in cases of supra-tentorial cysts (19%). The average gestational age for MRI scan in the MCBA group was 26 ± 5 weeks in comparison to ≥ 31st weeks in all other groups (p < 0.001). The current study describes a detailed picture of fetal brain MRI indications. Most patients were referred because of CNS anomalies. The impressive diversity of 16 separate entities emphasizes the expanding use of fetal brain MRI. Complicated MCBA pregnancies, which may have dramatic events, constitute a unique challenge due to early and repetitive MRI examinations and may serve as a role model for the contribution of fetal MRI during antenatal evaluation. The contribution of MRI to prenatal evaluation in various indications is discussed.

Neurosonology of the Developing Fetal Brain: Anatomic and Clinical Correlates of Disease

This lecture will begin by discussing the development of the fetal brain. We will look at the neuronal development with clinical correlates in all trimesters of pregnancy. Discussion of the advantages of looking at the developing fetal brain in the first trimester of pregnancy as a window into the detection of fetal anomalies will be discussed. Integration with MRI and CT imaging will be interspersed with sonographic discussion and interpretation. Common fetal CNS abnormalities will be outlined and their evolution during advancing gestation will be reviewed. Less common defects will be discussed with attention to the clues in imaging that make their diagnosis easier. The limitations of ultrasound imaging for certain CNS anomalies will be outlined in detail. This will include both fetal as well as maternal limitations. Tips and options for sonographic imaging will be interspersed within the lecture to allow the participant several options for imaging fetal anomalies with neurosonography and improving their diagnostic accuracy.

OC24.06: Absence of the choroid plexus of the IV ventricle in the first trimester as a predictor of posterior fossa anomalies and aneuploidies: a 3‐dimensional ultrasound study

There is an increasing interest in the sonographic detection of posterior fossa (PF) anomalies in the first trimester (1T) of pregnancy. However, there is poor agreement in the diagnostic criteria among different investigators. Our objective is to describe a qualitative reproducible sonographic feature that can be useful to predict pathology in the PF during the 1T of pregnancy. Two experienced operators, blinded to the final clinical outcome, retrospectively analysed stored 3D volume data sets from 68 1T fetuses (11 + 0-13 + 6w), including 14 with abnormal PF that were randomly added to the sample. The choroid plexus (CP) of the IV ventricle was assessed in midsagittal and axial planes by multiplanar navigation. It was classified as present or absent if the echogenic line between the brain stem and the cisterna magna was visible or not in both planes. 3D volume data sets were acquired transabdominally in 58 (85%) cases and transvaginally in the other 10 (15%). The CP of the IV ventricle was classified as present in 53 cases and as absent in 15 cases, with total agreement between the two observers in both axial and sagittal planes except for one case. The CP was absent in: 10 fetuses with aneuploidy (triploidy: 5; trisomy 13: 2; trisomy 18: 2; Turner syndrome: 1); 4 fetuses with CNS anomalies (open neural tube defects: 2; encephalocele: 1; Dandy-Walker malformation: 1); and 1 normal fetus (false positive). Qualitative assessment of the CP of the IV ventricle seems to be highly reproducible. This simple sonographic feature can facilitate the detection of PF anomalies, which are frequently associated with aneuploidies.

Focal triphasic sharp waves and spikes in the electroencephalogram.

There is a plethora of data in the EEG literature on the characteristics of the most prominent component of interictal epileptiform discharges (IED), namely the negative (fast) phase. Surprisingly, however, little attention has been drawn to the after-coming slow wave (ASW), and its pathological as well as clinical significance. In this paper, we will address the significance of prominent (high amplitude) ASW, giving rise to a triphasic morphology of the IED (focal triphasic sharp waves and spikes—FTSW). We will discuss this EEG pattern with respect to its clinical, neurophysiological, and neuropathological significance. This investigation was conducted on a heterogeneous group of patients at KKH, Ha'il, KSA. Our data revealed that FTSW were rare EEG events occurring primarily in the first two decades of life. Ninety percent of the patients with FTSW had epilepsy, presenting clinically with generalized convulsive seizures, often without partial onset. The majority of these patients responded favorably to anticonvulsant monotherapy. We were surprised to find that half of the patients with FTSW had chronic and/or static CNS pathology, particularly congenital CNS anomalies. Even though more than one mechanism may be involved in the pathogenesis of FTSW, we believe a deeply seated pacemaker as the source of this EEG pattern is the most compelling theory. The presence of FTSW should alert clinicians to the possibility of an underlying chronic and/or static CNS pathology, in particular congenital CNS anomalies, underscoring the significance of neuroimaging in the work-up of this population. Moreover, it is conceivable that the prominent ASW may contribute to the interictal intellectual dysfunction of these patients, justifying aggressive anticonvulsant therapy.

Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases.

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.

Spectrum of Central Nervous System Anomalies Detected by Fetal Magnetic Resonance Imaging; A 2 Year Study

Background: Magnetic resonance Imaging (MRI) is increasingly used for detailed visualization of the fetus as well as pregnancy structures although ultrasound(US) remains the predominant modality for evaluating disorders related to pregnancy overall. MRI does not have the limitations of US thanks to its multiplanar capability, lack of ionizing radiation, and excellent soft-tissue contrast. The most common indications for fetal MRI are neurological. MRI is commonly used to investigate underlying etiologies of brain abnormalities that are not detected by US. Cortical malformations, heterotopias and anomalies of the corpus callosum are well depicted by MRI. It can confirm the diagnosis of ventriculomegaly or other associated abnormalities not detected by sonography. Posterior fossa abnormalities that can be evaluated by prenatal MRI include Dandy-Walker syndrome, Dandy-Walker variant, mega cisterna magna (> 10 mm), arachnoid cyst and Chiaris malformation type II. Evaluation of the spinal column is important to detect abnormalities such as neural tube defects. Objectives: We intend to investigate the prenatal MRIs performed in our center for frequency of different central nervous system anomalies. Patients and Methods: In a cross sectional retrospective study, from September 2011 to December 2013 pregnant women referring for fetal MRI with suspected anomalies diagnosed in prenatal ultrasound were included in the study. All MRIs were done on a 1.5 T Siemens Avanto Magnet with a 4 channel body coil. Mothers with GA of 20 weeks or above were examined in the right tilt position. Sequences include T2 HASTE, Trufisp images 6 mm thick in axial, coronal and sagittal planes to mothers body. T2 HASTE and Trufisp images were also taken with 4 mm slice thickness relative to specific fetal body part being evaluated. T1 flash images were obtained in at least one plane based on clinical indication. We investigated the available images for any abnormality in central nervous system. Descriptive analysis was done on the collected data to achieve the index of frequency. Results: Most of patients (74%) were referred with primary impression of borderline ventriculomegally on ultrasound. A total of 11 patients out of 60 (18.3%) were found to have CNS anomalies and others were normal neurologically. Detected anomalies were as follows: 3 fetuses had complete agenesis of corpus callosum (27.2%), 2 had partial agenesis of corpus callosum (18.18%), 2 had myelomeningocele (18.18%) and 2 had Dandy-Walker variant (18.18%). Chari II malformation, aqueductal stenosis, tethered cord, schizencephaly and enlarged cisterna magna were anomalies presenting each in one patient (9%). 3 of the patients had concomitant findings. Conclusions: MRI is superior to ultrasound in detection of CNS anomalies which seems to over diagnose some brain anomalies and miss some others. Although most of the patients were provisionally diagnosed with ventriculomegally, the majority of them came as normal. Just 18.3% of fetuses had CNS anomalies with complete agenesis of corpus callosum as the most common finding. Other findings were partial agenesis of corpus callosum, myelomeningocele, Dandy-Walker variant, Chari II malformation, aqueductal stenosis, tethered cord, schizencephaly and enlarged cisterna magna, in order of frequency.

Ultrasound vs Magnetic Resonance in the Assessment of CNS Anomalies

ABSTRACT Central nervous system (CNS) malformations are some of the most comon congenital abnormalities. Long-term follow-up studies suggest that the incidence may be as high as 1 in 100 births. Imaging technologies have been remarkably improved and contributed to prenatal evaluation of fetal CNS development and assessment of CNS abnormalities. The routine examination of the fetal brain can be achieved with axial planes by conventional transabdominal ultrasonography. In order to provide a complete view of the different brain structures a detailed fetal neurosonogram requires additional coronal and sagittal views. Three-dimensional (3D) sonography should be performed transvaginally using the multiplanar approach. Transvaginal high-resolution 3D ultrasound can demonstrate cerebral fine vascular anatomy such as medullary vessels, intracranial calcification, vascular abnormalities. Parallel slicing provides a tomographic visualization of internal morphology similar to magnetic resonance imaging (MRI). Fetal MRI appears to be a useful adjunct to ultrasound to confirm or exclude certain abnormalities. MRI is a valuable complementary tool to detailed neurosonography which allows an evaluation of the normal brain maturation from the second trimester. It also offers a higher diagnostic performance for some congenital abnormalities such as cortical development or posterior fossa assessment. How to cite this article Crnogorac S, JuriÓiƒ A, Grdiniƒ A. Ultrasound vs Magnetic Resonance in the Assessment of CNS Anomalies. Donald School J Ultrasound Obstet Gynecol 2013;7(4):496-499.

Positive sharp waves in the EEG of children and adults

Interictal epileptiform discharges (IEDs) with negative polarity have been extensively studied in the EEG literature. However, little attention has been drawn to IED with positive polarity [positive sharp waves (PSWs)]. In this paper, we discuss pathophysiological, neuroimaging, and clinical correlates of this pattern in a heterogeneous group of children and adults who demonstrated PSW in their scalp EEG. We prospectively reviewed the EEGs of 1,250 patients from a heterogeneous population over a period of 1 year. Thirty-one patients had PSW in their EEG. We documented EEG parameters as well as demographic, clinical, and neuroimaging data. Statistical analysis was performed to correlate the aforementioned data. The analysis showed that PSW is an epileptogenic pattern with localizing significance, occurring primarily in the younger age groups. Furthermore, there was a strong association of PSW with chronic and/or static CNS pathology, in particular, congenital CNS anomalies, often accompanied by psychomotor retardation. Patients with "multifocal'' PSW invariably exhibited severe intellectual and motor deficits associated consistently with a variety of congenital CNS insults. PSW is a rare and under-reported EEG abnormality which, similar to negative IED, signifies focal epileptogenecity. The presence of PSW should prompt neuroimaging studies to investigate an associated chronic/static CNS pathology, in particular, congenital CNS anomalies. This association is particularly strong when PSW is multifocal in which case patients present with severe intellectual and motor deficits.

Expanding the spectrum of phenotypes associated with germline PIGA mutations: A child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities

Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family.

Outcome following selective fetal reduction in monochorionic and dichorionic twin pregnancies discordant for structural, chromosomal and genetic disorders

To investigate the indications for offering selective fetal reduction in monochorionic (MC) and dichorionic (DC) twins and to correlate obstetric outcome with the antenatal procedure. All cases of MC and DC twins discordant for structural anomalies and for chromosomal/genetic abnormalities were included. Selective reductions performed for twin-to-twin transfusion syndrome or growth restriction were excluded. For DC twins, feticide was achieved using intracardiac injection of potassium chloride (KCl). For MC twins, bipolar cord occlusion (BCO), interstitial laser or radiofrequency ablation (RFA) was used. There were 121 twin pregnancies discordant for structural and chromosomal abnormalities. Only 88 (56 were MC twins and 32 were DC twins) had selective reduction. For both MC and DC twins, the leading indication for selective reduction was structural anomalies with CNS malformations the most common. For all MC fetal reduction techniques, the overall pregnancy loss rate (<24weeks) was 8.9% with RFA having the lowest procedure loss rate (7.7%). The preterm delivery rate was lowest with reduction in DC pregnancies. The live birth rates for MC twins were >87% and 100% for DC twins. Selective reduction in MC pregnancies carries an increased procedure-related and preterm delivery rate compared with DC pregnancies. The main indication for selective reduction was structural malformations, with a predominance of CNS anomalies.

English

OBJECTIVES: Purpose of our study was to determine the detection rate of congenital anomalies in second trimester by single prenatal ultrasound screening in an unselected population and to evaluate the subsequent pregnancy outcome and to compare the results with published series using standardized criteria. SUBJECTS AND METHODS - One thousand pregnant women at 18-22 weeks' gestation were screened by prenatal ultrasound examination. We compared these sonographic reports with pregnancy outcomes established by postnatal echocardiography and ultrasound examinations of neonates and autopsy for dead fetuses. Statistical analysis was performed on two units; malformed fetus and malformation itself. RESULTS - A total of 27 fetuses with 30 anomalies were identified by prenatal ultrasound. Prospectively 2 babies with 2 anomalies were found to be normal. On postnatal examination 13 babies were found to have 14 anomalies which could not be detected by ultrasound. Thus the sensitivity of ultrasound in detecting congenital anomalies and anomalous fetuses was 66.6% and 67.5% respectively. Highest detection rate was observed for CNS anomalies (88.8%) but that of craniofacial and musculoskeletal anomalies was not very satisfactory (33% in each system). CONCLUSION -This study shows rate of detection of fetal anomalies is satisfactory for most organ systems except cardiac, musculoskeletal and craniofacial malformations.

Major structural birth defects in children aged 0–2 years in the Gaza Strip: a cross-sectional study

Background No information is available about the prevalence, phenotypes, and regional differences in major structural birth defects in children aged 0–2 years in the Gaza Strip, occupied Palestinian territory (oPt). As part of a wider reproductive health initiative that includes the introduction of uniform recording protocols in the main paediatric facilities in the Gaza Strip and the management of major structural birth defects, we undertook this study to identify and report missing information. Methods Our study population was selected from all patients aged 0–2 years with major structural birth defects who were referred for surgery during the first 6 months of 2010 to one of five main paediatric hospitals (Nassr, Rantissi, Dorra, European Gaza Hospital, and Emirati) or to one of two paediatric surgical departments (Al-Shifa and European Gaza Hospital) in the Gaza Strip. Of these referrals, those with major structural birth defects (congenital heart disease, and renal, gastrointestinal, and CNS anomalies) were selected by the paediatrician for inclusion. From the children's records, we obtained the demographic details, risk factors associated with birth defects, family history of birth defects, and type of congenital anomalies noted during clinical examination by a skilled neonatologist and in subsequent investigations. We classified birth defects according to the primary defect, using International Statistical Classification of Diseases and Related Health Problems 10th Revision as a reference. We used a specially prepared form for recording the abstracted data, which were then analysed with SPSS (version 13.0). We obtained medical ethics approval for the study from the Helsinki Committee, Gaza Strip. Findings Of 5254 children referred to one of the paediatric hospitals, 331 (6%) had major structural birth defects. A further 58 children were referred directly to one of the surgical units. Of 331 reported major birth anomalies, the most frequent were heart (148 [45%]), renal (49 [15%]), gastrointestinal (43 [13%]), and CNS and neural tube defects (40 [12%]). The estimated overall prevalence of severe structural birth defects was eight per 1000 in children aged 0–2 years. We noted significant regional differences in prevalence of birth defects—the highest prevalence was reported in the north of the Gaza Strip (nine per 1000) and the lowest in Khan Younis (three per 1000; p=0·009). Interpretation Some types of major structural birth defects might have been under-represented in our survey (such as those affecting the eyes and ears) because some children were treated abroad. However, the data we have presented will provide a baseline for future monitoring of the frequency of major structural defects in the Gaza Strip. Funding Italian Cooperation.

1056 Mega Cisterna Magna Diagnostic Dilemma

Background and AimThe prenatal diagnosis of posterior fossa dysgenesis remains challenging. Mega-cisterna magna (MCM) is applied to prominence of the retro-cerebellar CSF space and may not be associated with abnormalities....

P13.04: Prenatal diagnosis of fetal midline CNS anomalies by the combination of 2D/3D ultrasound and fetal magnetic resonance

P13.04: Prenatal diagnosis of fetal midline CNS anomalies by the combination of 2D/3D ultrasound and fetal magnetic resonance

Prenatal Neurologic Anomalies

The low prevalence of fetal CNS anomalies results in a restricted level of exposure to, and limited experience for most obstetricians involved in, prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way may increase the detection rate of fetal CNS anomalies, thus promoting correct referral to tertiary care centers offering patients a multidisciplinary approach to the condition. The aim of this review is to elaborate on the prenatal sonographic diagnosis and outcome of various CNS malformations. Detailed neurosonographic investigation has become available through high-resolution vaginal ultrasound probes and the development of a variety of 3-dimensional (3D) ultrasound modalities, such as ultrasound tomographic imaging. In addition, fetal magnetic resonance imaging is particularly helpful in the detection of gyration and neurulation anomalies, and disorders of the gray and white matter. Isolated mild ventriculomegaly is a rather common finding with good overall outcome. With an increasing diameter of the atria, however, and especially with the presence of associated malformations, long-term neurodevelopmental and behavioral outcome is disturbed in about 15% or more of cases. In view of recent developments in fetal therapy for neural tube defects, there is a clear need for a high level of ultrasound screening, work-up and counseling in tertiary care centers to identify those cases that might benefit from in utero intervention. The failure of prosencephalic midline induction and development results in midline defects ranging from alobar holoprosencephaly to isolated corpus callosum defects. The detection of callosal abnormaties is enhanced by 3D ultrasound, but counseling on neurodevelopmental outcome remains challenging. The Dandy-Walker spectrum includes isolated megacisterna magna, Blake's pouch cyst, hypoplasia of the vermis and Dandy-Walker malformation. Except for complete agenesis of the vermis associated with fourth ventricle cyst formation, data on long-term outcomes for the various conditions is largely lacking. Congenital cytomegalovirus (CMV) results in the highest incidence of children born with, or developing, long-term neurologic conditions. If proof of fetal infection has been delivered, microcephaly, cortical malformations, and intraparenchymal cysts show a strong correlation with poor outcome. Fetuses with CMV-related ultrasound abnormalities might benefit from maternal transplacental treatment. The aneurysm of the vein of Galen, a vascular malformation of the brain, often results in high cardiac output failure. After neonatal arterial embolization, survival is about 50% with normal neurologic development in 36% of cases. Over 50% of intracranial tumors are teratomata, presenting as fast-growing heterogeneous solid-cystic masses with calcifications. Most intracranial hemorrhages are related to the ventricular system, and prognosis is often poor, particularly in cases involving parenchymal and subdural bleeding. Proliferation disorders of the brain are often characterized by microcephaly. Their etiology is heterogeneous and prenatal diagnosis is often made late in gestation.

Molecular cytogenetic characterization and genotype/phenotype analysis in a patient with a de novo 8p23.2p23.3 deletion/12p13.31p13.33 duplication

Genomic copy number imbalances are being increasingly identified as an important cause of intellectual disability (ID) and behavioral disturbances. This article reports the clinical features, and long term follow-up of a patient with neurodevelopmental, cognitive, and behavioral abnormalities associated with facial dysmorphism, CNS anomalies, and epilepsy. The karyotype was normal; array CGH testing revealed a de novo cryptic aberration with a terminal 8p23.2p23.3 deletion, and a concomitant 12p13.31p13.33 duplication, of 6.86 Mb, and 8.49 Mb, respectively. Our patient clinical features are compared to those of partial 8 monosomy and/or partial 12p trisomy cases reported in literature, in order to establish genotype-phenotype correlations. For some features, for example, electroencephalogram (EEG) abnormalities and epilepsy, both abnormalities seem to make a contribution, while most phenotypic traits have been assigned to 8p monosomy or to 12p trisomy, contributing to a tentative phenotype map for partial monosomy of the short arm of chromosome 8, and trisomy of the short arm of chromosome 12.

Reply to Chakrabarti et al.: Corneal angiogenesis in patients with null FOXC1 variants

In the 15 years since transcription factor mutation, and subsequently dosage alterations, were shown to account for a proportion of Axenfeld–Rieger syndrome cases, novel phenotypes continue to be defined. As illustrated by the spectrum of FOXC1 -attributable CNS anomalies (1, 2), these are frequently present in a subset of cases and only identified by meticulous phenotyping. Our original article in PNAS (3) demonstrated that a proportion of patients with a mutation or altered FOXC1 gene dosage exhibited corneal angiogenesis, confirming our extensive data from multiple murine mutants regarding Foxc1’s role in maintaining corneal avascularity. … [↵][1]1To whom correspondence should be addressed. E-mail: t-kume{at}northwestern.edu. [1]: #xref-corresp-1-1

Encephalocraniocutaneous lipomatosis (ECCL) - a case report

Aims: Encephalocraniocutaneous lipomatosis (ECCL) is a very rare sporadically occuring neurocutaneous syndrome with unilateral or bilateral manifestation, predominantly affecting the head. It is characterized by skin lesions (naevus psiloliparus, alopecia, subcutaneous fatty masses, nodular skin tags), ocular anomalies (mainly choristomas) und CNS anomalies (intracranial and spinal lipomas, intracranial vessel defects). About two-thirds of patients have a normal development or mild retardation only, and half of them have seizures. Jaw tumours and bone cysts may be associated.