Infracoccygeal/transperineal window: new method to prenatally diagnose and classify level of anal atresia.

OBJECTIVES: To introduce a two-dimensional sonographic method to assess the fetal anus, and to evaluate the feasibility of this method to diagnose anal atresia prenatally and identify the presence or absence of anoperineal fistula (in males) and anovestibular fistula (in females). METHODS: This was an observational study of suspected cases of anal atresia referred to a single center in Israel between August 2018 and October 2023. In addition to conventional evaluation of the perineum in the axial plane, fetuses referred to our center for suspected malformation were scanned with a new method termed the 'infracoccygeal/transperineal window'. This window consisted of a midsagittal view of the fetal pelvis, including the distal rectum and the anal canal. Normal anatomy was confirmed when the anal canal was continuous with the rectum and terminated at the expected location on the perineum. In female fetuses, the normal anal canal runs parallel to the vaginal canal and diverges posteriorly, terminating at the perineal skin, distant from the vestibule. In male fetuses, the normal anal canal diverges posteriorly in relation to the corpora cavernosa, terminating at the perineal skin, distant from the scrotum. High anal atresia was identified when a blind-ending rectal pouch was demonstrated in the pelvis without a fistula to the perineum or vestibule. Low anal atresia was determined when a rectal pouch was continuous with an anteriorly deflected fistula. In females, the fistula converges with the vaginal canal, terminating at the vestibule; in males, the fistula deflects anteriorly, terminating at the base of the scrotum. Postnatally, the diagnosis and type of anal atresia were confirmed through physical examination with direct visualization of the fistula, radiographic studies, surgical examination and/or postmortem autopsy. RESULTS: Of the 16 fetuses diagnosed prenatally with anal atresia, eight were suspected to have low anal atresia and eight were suspected to have high anal atresia. The median gestational age at diagnosis was 23 (range, 14-37) weeks. All cases showed additional structural malformation. Eleven patients opted for termination of pregnancy, of which four had low anal atresia and seven had high anal atresia. Postnatal confirmation was not available in four cases due to curettage-induced mutilation or in-utero degradation following selective termination of the affected twin, leaving 12 cases for analysis, of which seven were diagnosed with low anal atresia and five with high anal atresia. In these 12 cases, all prenatal diagnoses were confirmed as correct, rendering 100% sensitivity and 100% specificity in this high-risk fetal population. CONCLUSIONS: The infracoccygeal/transperineal window is an effective method to detect and classify the level of anal atresia prenatally. This may improve prediction of postnatal fetal continence and optimize prenatal counseling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal neurosonography as accurate tool for diagnosis of brain involvement in tuberous sclerosis.

OBJECTIVE: To demonstrate the potential utility of dedicated neurosonography for the diagnosis of fetal brain involvement in tuberous sclerosis complex. METHODS: This was a multicenter retrospective study of fetuses at high risk for tuberous sclerosis complex. Dedicated neurosonographic, fetal magnetic resonance imaging (MRI) and postnatal reports were reviewed. Data collected included reason for referral, gestational age at which cardiac rhabdomyoma was first suspected and final number of cardiac rhabdomyomas detected on dedicated imaging. We searched for tuberous sclerosis complex-related brain involvement, defined as the presence of one or more of the following findings: white-matter lesions; subependymal nodules; cortical/subcortical tubers; and subependymal giant-cell astrocytoma. RESULTS: We included 20 patients at high risk of tuberous sclerosis complex, of whom 19 were referred for the presence of cardiac rhabdomyomas and one for a deletion in chromosome 16 involving the tuberous sclerosis complex gene locus. Cardiac rhabdomyomas were diagnosed at a mean gestational age of 27 + 2 weeks (range, 16 + 0 to 36 + 3 weeks) and the mean number of cardiac rhabdomyomas per patient was 4 (range, 1-10). Brain involvement was present in 15 fetuses, in 13 of which the disease was confirmed in one or more of the following ways: chromosomal microarray analysis (n = 1), exome sequencing (n = 7), autopsy (n = 4), clinical tuberous sclerosis complex in the newborn (n = 4) and a sibling diagnosed with clinical tuberous sclerosis complex (n = 1). In two cases, the disease could not be confirmed: one was lost to follow-up and autopsy, following termination of pregnancy, was not performed in the other. Among the five cases without brain findings, tuberous sclerosis complex was confirmed in three by exome sequencing (n = 2) and/or autopsy findings (n = 2). The two remaining cases had normal exome sequencing; one case had five cardiac rhabdomyomas, which was a highly suggestive finding, while in the final case, the autopsy was considered normal, representing the only false-positive case in our cohort. CONCLUSIONS: Contrary to current literature, dedicated neurosonography appears to be effective in the diagnosis of brain involvement in fetuses at risk of tuberous sclerosis complex and should be used as the first-line approach. Although the number of cases in which MRI was performed was small, it seems that, in the presence of ultrasound findings, the added value of MRI is low. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

BACKGROUND AND PURPOSE: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book Pediatric Neuroimaging from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation. MATERIALS AND METHODS: This is a multicenter, international, retrospective study. We assessed the patients' medical records, prenatal ultrasounds, MR images, genetic findings, and postmortem results. We reviewed the medical literature for all studies depicting medullary malformations and evaluated cases in which a dorsal medullary protuberance was described. RESULTS: We collected 13 patients: 3 fetuses and 10 children. The medullary caps had multiple characteristics. Associated brain findings were a rotated position of the medulla, a small and flat pons, cerebellar anomalies, a molar tooth sign, and agenesis of the corpus callosum. Systemic findings included the following: polydactyly, hallux valgus, large ears, and coarse facies. Postmortem analysis in 3 patients revealed that the cap contained either neurons or white matter tracts. We found 8 publications describing a dorsal medullary protuberance in 27 patients. The syndromic diagnosis was Joubert-Boltshauser syndrome in 11 and fibrodysplasia ossificans progressiva in 14 patients. CONCLUSIONS: This is the first study to describe a series of 13 patients with medullary tegmental cap dysplasia. The cap has different shapes: distinct in Joubert-Boltshauser syndrome and fibrodysplasia ossificans progressive. Due to the variations in the clinical, imaging, and postmortem findings, we conclude that there are multiple etiologies and pathophysiology. We suggest that in some patients, the pathophysiology might be abnormal axonal guidance.

Malformation of cortical development with abnormal cortex: early ultrasound diagnosis between 14 and 24 weeks of gestation.

OBJECTIVE: To describe neurosonographic findings diagnostic or highly suggestive of the presence of malformations of cortical development involving the cortex that may be identified before 24 weeks of gestation. METHODS: This was a retrospective single-center study of fetuses referred for neurosonography, during 2012-2019, with an abnormal cortical or sulcation pattern diagnosed early in the mid trimester. Stored files were analyzed for demographic data, abnormal brain findings, non-central nervous system abnormalities, final diagnosis and postnatal outcome. RESULTS: The study cohort included 20 fetuses, with a mean gestational age at diagnosis of 18.7 (range, 14.4-23.6) weeks, in 11 of which the diagnosis was made before 20 weeks of gestation. Reasons for referral were: midline anomaly (n = 7), ventriculomegaly (n = 4), infratentorial findings (n = 3), suspected malformation of cortical development (n = 3), 'abnormal brain' (n = 2) and skeletal dysplasia (n = 1). On neurosonography, both the sulcation pattern and the cortical layer were abnormal in four cases, only the sulcation pattern was considered abnormal in seven and only the cortical layer was abnormal in nine. Nineteen fetuses presented with associated central nervous system anomalies and six also had non-central nervous system malformations. One case was recurrent. Eighteen parents opted for termination of pregnancy, including one selective termination in a twin pregnancy, and two fetuses were liveborn. CONCLUSIONS: Familiarity with fetal brain anatomy and its early sonographic landmarks allowed early diagnosis of malformations involving cortical development. These patients are likely to represent the most severe cases and all had associated malformations. The presence of an abnormal cortical layer and/or abnormal overdeveloped sulci appear to be early signs of malformation of cortical development. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay.

Recently, bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have been described in three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities. Here we report an additional subject with this condition identified by whole-exome sequencing. Our findings support the association between this disorder and neonatal cholestasis with distinct liver pathology. Furthermore, we provide functional data on two novel missense substitutions and expand the phenotype to include mild developmental delay, skin hyper-elasticity, and hypervitaminosis D.

Very Early In-Utero Diagnosis of Walker-Warburg Phenotype: The Cutting Edge of Technology.

BACKGROUND: Walker-Warburg phenotype is a severe and lethal autosomal recessive disorder, belonging to a group of congenital malformations defined as abnormal pial basement membrane formation. So far, prenatal diagnosis was considered possible only during late pregnancy. METHODS: First trimester assessment of a pregnancy suspected to be affected by Walker-Warburg phenotype, using a high-resolution transvaginal ultrasound probe (6-12 MHz), T2 MR imaging (1.5T), molecular genetics and histopathology. RESULTS: Very early diagnosis of the Walker-Warburg phenotype at 11 weeks of gestation proved possible by depicting the classic signs of this entity, confirmed by molecular genetics, post-abortion MR imaging and histopathology. CONCLUSION: Advancements in ultrasound equipment and technology, molecular genetics and histopathology have made very early detection of this syndrome possible, thus shedding new light on the natural history of this malformation.

Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero.

OBJECTIVE: To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation. METHODS: A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation. RESULTS: In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive value (PPV) was 56%. Combination of the HC and FCD criteria raised the PPV to 78%, decreasing the number of false positives from 11 to four, without missing any of the 14 micB cases. CONCLUSIONS: Fetal vertical cranial biometric assessment in the mid-sagittal plane is feasible and correlates well with gestational age. In our series, a vertical cranial deformation was a frequent cause of a false Fmic diagnosis made on the basis of HC alone. Combination of the new vertical cranial biometric measurement with HC measurement can exclude these cases and thus improve diagnostic accuracy for Fmic. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Region-specific reductions in brain apparent diffusion coefficient in cytomegalovirus-infected fetuses.

OBJECTIVE: To evaluate the effects of cytomegalovirus (CMV) infection on apparent diffusion coefficient (ADC) values of the fetal brain in utero. METHODS: In this retrospective analysis we compared 58 fetal head magnetic resonance imaging (fhMRI) scans of PCR-verified CMV-infected fetuses, obtained in 2008-2012, with those of a normal control group of 36 gestational age (GA)-matched uninfected fetuses scanned between 2006 and 2012. Estimated GA at infection ranged from 1 to 32 weeks, and fhMRI was performed at 24 to 38 weeks. The frontal, parietal, temporal and occipital lobes (mainly white matter), basal ganglia, thalamus, pons and cerebellum were analyzed by assessing ADC values. Two pregnancies were terminated and postmortem confirmation was available in these cases. RESULTS: ADC values of CMV-infected fetuses correlated significantly and negatively with GA in all brain regions except the basal ganglia. The cerebellum had the greatest reduction (r = -0.52, P < 0.0001). Maternal age correlated positively with ADC in the frontal lobe (P < 0.05). GA at infection and overt pathological changes did not affect ADC significantly. Compared with non-infected fetuses, ADC values of affected fetuses were significantly reduced in the frontal (P < 0.0001), parietal (P < 0.0001), occipital (P = 0.0005) and temporal (P = 0.001) lobes and thalamus (P = 0.006). CONCLUSION: CMV infection of the fetal brain results in a highly significant, region-dependent reduction of ADC values in the frontal, parietal, occipital and temporal lobes and thalamus, probably reflecting hypercellularity and inclusion bodies in damaged areas. Further studies are needed to determine if reduction in ADC values may serve as a prognostic factor in CMV-infected fetuses. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

OBJECTIVE: To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. METHODS: Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. RESULTS: Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively. CONCLUSIONS: The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Relative value of clinical, laboratory and imaging tools in diagnosing pediatric acute appendicitis.

OBJECTIVE: Aim of the study was to evaluate the relative value of the tools used to diagnose suspected acute appendicitis (AA) in children. METHODS: A retrospective review of data from 1 848 children admitted to the Pediatric Surgery Department between 2004 and 2008 in our university-affiliated medical center was conducted. A total of 780 children underwent appendectomy at first presentation. Of these patients, 75 children required removal of their appendix during laparotomy for other reasons and 19 had appendectomy following peri-appendicular abscess and were excluded from the study. The study included 686 children (2-16 years of age) with presumed AA managed by appendectomy. Clinical, laboratory, and imaging data were collected and compared to pathology results. RESULTS: Of the 686 children who underwent surgery for suspected AA, 34 (5%) had a normal appendix (negative appendectomy rate). No statistical differences were found between normal and AA groups with regard to vomiting, diarrhea, pain duration, and peritoneal signs on admission. Children in the AA group were younger (10.9±3.2 vs. 12.1±2.3 years, p=0.004), had higher fever (36.9±0.7°C vs. 37.4±0.8°C, p=0.004), WBC (14.8±4.8 vs. 10.5±4.6×103/mL, p<0.0005), and neutrophil counts (77.2±11.1% vs. 64.0±15.9%, p<0.0005) on admission, and larger appendicular diameters on ultrasound (US) examination (0.9±0.2 cm vs. 0.7±0.08 cm, p<0.0005). The parameters with the highest positive predictive values for AA were WBC (>10×10 (3)/mL), neutrophil (>66%) count on admission (positive predictive value [PPV]=0.971 and 0.975, respectively), and appendicular diameter on US (>6 mm; PPV=0.968). These 3 parameters combined had a PPV of 0.991. CONCLUSIONS: The results of laboratory tests (WBC, neutrophils) and imaging (US) contributed far more than clinical signs and symptoms (pain duration, vomiting, diarrhea, fever, and peritoneal signs at first physical examination) to the correct diagnosis of AA in children. When these 3 parameters were positive, the probability of a false positive (normal appendix) was only 1%. The contribution of US was particularly high as it was used primarily in patients in whom the diagnosis was in doubt and its results matched the final diagnosis better than diagnoses based on clinical signs and symptoms alone. It provides the additional benefit of no radiation exposure.

Can syndromic macrocephaly be diagnosed in utero?

OBJECTIVES: To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly. METHODS: We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated. RESULTS: Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached. CONCLUSIONS: When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign.

Prenatal diagnosis of congenital agenesis of the fetal portal venous system.

OBJECTIVE: To describe the prenatal diagnosis and review our experience of fetal congenital agenesis of the portal venous system (CAPVS) and to review the current literature on this poorly documented vascular malformation. METHODS: This was a retrospective survey covering the 12-year period between 1996 and 2008. The database of a single, large, ultrasonographic tertiary academic referral center in Israel was analyzed and cases with a prenatal diagnosis of CAPVS were identified. All fetuses underwent detailed biometric and structural ultrasound examinations and a precise anatomical description of the fetal umbilical, portal and hepatic venous system was noted, as well as the presence of aberrant vessels, shunt location and the presence or absence of the DV. Results of fetal echocardiography, karyotyping and toxoplasma, rubella, cytomegalovirus and herpes evaluations were determined. Medical records were evaluated. Diagnosis was confirmed by pathology, postmortem venography or neonatal ultrasound or venography. Liveborns were examined by a certified neonatologist and long-term follow-up from pediatric gastroenterology units was determined. RESULTS: Nine cases with CAPVS were studied. In all cases an aberrant umbilical-portal vein was the primary indication for detailed portal system evaluation. Five fetuses demonstrated total CAPVS (Type I) and four showed partial agenesis of the portal vein (Type II). Among the five Type I fetuses, there was a shunt from the umbilical vein to the inferior vena cava in three (60%), to the right atrium in one and to the coronary sinus in one. In this group, in only one case could we delineate a common confluence between the splenic vein and the superior mesenteric vein shunting to the inferior vena cava. In four cases termination of pregnancy was performed due to additional findings: one case with hydrothorax, ascites and mitral atresia, one with cleft lip/palate and one with trisomy 21. One case had no additional anomalies, but the parents elected to terminate the pregnancy. All four of the Type II fetuses had a portosystemic shunt: in two cases to the right atrium, in one to the iliac vein and in one to the right hepatic vein. In three, the shunt resolved spontaneously. In only one case was abnormal liver function present over a follow-up period of 2-10 years. CONCLUSION: CAPVS can be detected prenatally. An abnormal course of the umbilical vein necessitates prompt sonographic evaluation of the umbilical-portal venous system and meticulous investigation for additional anomalies. Complete CAPVS may be associated with remote clinical consequences of which the parents should be informed. Partial CAPVS has a favorable prognosis.

Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation.

BACKGROUND: Intrauterine fetal death is an agonizing, often unpredictable event. Autopsies of stillborn fetuses, including placentas, are performed to clarify the cause of death. Autopsy results are not always easily understood by the patients or their healthcare providers. OBJECTIVE: To evaluate placental causes of death in stillbirths based on autopsy and placental findings that are related to maternal underperfusion, fetal underperfusion, or inflammatory etiologies in hierarchical order. METHODS: Retrospective review of 120 autopsy reports of singleton stillborn fetuses and placentas from 23 to 40 weeks of gestation. RESULTS: Among the placental causes of death there were 54(51%) cases with direct cause or major contributor to death in the etiology of maternal vascular supply abnormalities, 28(26%) cases in the etiology of fetal vascular supply abnormalities and 13(12%) in the etiology of inflammatory lesions. Maternal vascular supply abnormalities were more common in preterm stillbirths and fetal vascular supply abnormalities were more common among term stillbirths. In 88% of stillbirths, the direct cause or a major contributor to death was found in the placentas. The incidence of unexplained death was 8%. CONCLUSIONS: Pathological analysis of the placenta is essential for clarifying causes of stillbirths. Using specific simplified categories for abnormal placental findings may increase the benefits of the autopsy report.

Thick fetal corpus callosum: an ominous sign?

OBJECTIVE: Anomalies of the corpus callosum are frequently diagnosed during pregnancy, but a thick corpus callosum is a rare finding and its significance is not clear. We aimed to assess the significance of thick fetal corpus callosum by reviewing our experience of such cases. METHODS: The records of all fetuses with anomalies of the corpus callosum referred to the prenatal diagnosis units of two university hospitals from 2000 to 2007 were reviewed. Nine fetuses with a thick corpus callosum were identified. RESULTS: In all cases there were associated abnormalities: macrocephaly, ventriculomegaly, vermian agenesis, abnormal sulcation or encephalocele. Four pregnancies were terminated and in each of these cases the autopsy confirmed dysmorphic features and additional brain abnormalities. Five infants were delivered; two died shortly after birth, one suffers from mental retardation, one had neonatal convulsions and one is developing normally. CONCLUSIONS: A thick fetal corpus callosum is usually associated with other brain anomalies and is part of a neurogenetic syndrome in most cases.

Juvenile onset of primary low-grade cutaneous B-cell lymphoma.

BACKGROUND: Cutaneous lymphomas rarely occur in children and adolescents, and are mostly of the T-cell lineage. Low-grade primary cutaneous B-cell lymphoma (CBCL) is extremely rare in individuals under 18 years old. Only 11 patients under 20 years old have been reported in the literature. OBJECTIVES: To evaluate the number of patients younger than 18 years with primary CBCL diagnosed at our centre and to investigate its clinicopathological features, treatment and course in this age group. METHODS: We reviewed the files of all 90 patients with primary CBCL who attended the Department of Dermatology of our tertiary care university-affiliated centre from 1992 to 2007. RESULTS: Four patients who met study criteria were identified: three girls and one boy. Mean age at diagnosis was 16.6 years (range 16-17). Three patients had cutaneous marginal zone lymphoma (CMZL), and one had a spindle-cell (sarcomatoid) lymphoma, most probably follicular centre cell type. All were treated with the standard regimen used in adults. The mean duration of follow up was 45 months. No extracutaneous progression was noted. At present two of the four patients are in complete clinical remission. CONCLUSIONS: In Israel, primary CBCL apparently occurs more often in young patients than reported in the literature. CMZL is the most frequent type. Long follow up is mandatory to assess the biological behaviour of CBCL in the paediatric/adolescent age group.

Prenatal diagnosis of malformations of cortical development by dedicated neurosonography.

OBJECTIVE: Malformations of cortical development (MCD) are rarely diagnosed in utero. We describe and compare the ultrasonographic and pathology findings in a cohort of fetuses with MCD. METHODS: Fetuses with MCD were identified among all fetuses evaluated for suspected brain anomalies at the Fetal Neurology Clinic, and the ultrasonographic findings were compared with the results of the pathology examination. RESULTS: We suspected the presence of MCD by ultrasonography in 23 fetuses. The mean gestational age at the time of ultrasound diagnosis was 26.2 (range, 18-40) weeks. The ultrasonographic findings leading to the diagnosis of MCD were abnormally overdeveloped gyri and sulci for gestational age (n = 7), delay in sulcation (n = 5), abnormally thin cortex (n = 5) abnormally wide and broad sulci (n = 3), bulging into the lateral ventricle (n = 1), cortical cleft (n = 1), and multiple intraparenchymal echogenic nodules (n = 1). All fetuses had associated central nervous system (CNS) and/or non-CNS anomalies. Pathology examination (performed in 17 fetuses) confirmed MCD in 16. CONCLUSIONS: Cortical malformations can be diagnosed in utero by ultrasonography based on the presence of specific deviations from the normal pattern of development. The identified cases may represent the more severe forms in the MCD spectrum. The pathology findings do not always conform to the current classification systems of MCD but help in differentiating between possible genetic and acquired etiologies and in some cases provide a definitive syndromic diagnosis.