Frequency Of Anomalies Research Articles

Concordant Underexpression of Fanconi Anemia/BRCA1 Pathway Proteins in a Major Proportion of Myelodysplastic Syndromes

Introduction:BRCA1 plays a key role in maintaining genomic stability and interacts directly with several proteins that regulate hematopoietic stem cell functions and are part of the Fanconi anemia (FA) double-strand break (DSB) repair pathway. Loss of BRCA1 in murine bone marrow causes hematopoietic defects similar to those seen in FA (Vasanthakumar, Blood 2016). BRCA1 is highly expressed in hematopoietic tissues, whereas its expression is lost in CML (Deutsch et al, Blood 2003) and t-AML (Scardocci et al, Br J Cancer 2006). Since FA is associated with an increased risk of developing myelodysplastic syndromes (MDS), we examined the protein expression of BRCA1 and three other important components of the FA DNA repair pathway, as well as PARP-1, whose co-alteration with BRCA causes synthetic lethality.Methods:We recently established a tissue microarray (TMA) with bone marrow biopsies from 119 MDS patients, 40 AML patients, and 11 normal controls. Biopsy material was retrieved from the Institute of Pathology, Heinrich-Heine-University Düsseldorf, Germany. The TMA was produced at SciLifeLab Tissue Profiling Facility in Uppsala, Sweden. Immunohistochemistry (IHC) protocols were established in our lab for the detection of BRCA1, BRCA2, FANCD2, H2AX, and PARP1. Semi-quantitative analysis was done according to Remmele-Stegner immunoreactive score (IRS) with a point system from 0 to 12. Expression was categorized as absent (0-2), weak (3-4), moderate (5-8) or strong (9-12). For correlating protein expression with clinical data from the Düsseldorf MDS Registry, samples were dichotomized into 'low expression' (1-4) and 'higher expression' (5-12). Prognostic analysis was restricted to 80 MDS patients who did not receive disease-modifying therapy.Results:Similar to normal controls, most patients with AML showed strong expression of the proteins under consideration (Fig. 1). In contrast, low expression was found in about 60% of MDS patients. Most MDS patients showed concordant, dichotomous expression of all five proteins (either all up or all down). Correspondingly, the protein expression landscapes look similar (Fig. 1). Almost perfect concordance was noted for PARP1 and H2AX.Low expression of FA/BRCA pathway proteins was not correlated with MDS type (WHO 2008) or IPSS-R risk group. Patients with higher expression of at least 3 of the 5 proteins survived longer (45 vs. 26 months) and had a longer time to AML development (median not reached at 180 months vs. 53 months), but the differences did not reach statistical significance (p=0.108 and p=0.159, respectively). Interestingly, patients with low expression of PARP1 were significantly more likely to show any chromosomal aberration (p=0.02) or an unfavourable karyotype (intermediate, high-risk or very high risk according to IPSS-R) (p=0.016). The same was true for patients with low expression of H2AX (p=0.013 and p=0.01).Conclusions:This is the first TMA-based investigation of FA/BRCA pathway protein expression in MDS. In stark contrast to AML, 60% of MDS patients showed low protein expression in a concordant manner. This could reflect synexpression of genes that share common cis- and trans-acting control elements. Alternatively, it could be the result of aberrant splicing, since at least 50% of MDS patients have spliceosome mutations that render a large spectrum of messenger RNAs susceptible to nonsense-mediated decay. Abnormal splicing factors may also influence the stability (and thus expression) of certain proteins through abnormal protein-protein interactions. Further IHC analyses will show whether the dichotomous protein synexpression pattern we observed in MDS extends to proteins that are unrelated to DNA maintenance.Underexpression of FA/BRCA pathway proteins may cause chromosomal instability, as suggested by our finding of significantly more frequent karyotype anomalies in patients with low PARP1 or H2AX expression. This is in accordance with the known role of H2AX as suppressor of oncogenic chromosome translocations, and with an accelerating effect of PARP1 deficiency on centrosome amplification in BRCA1-deficient cells. FA/BRCA pathway protein underexpression may not only contribute to a better understanding of MDS versus AML pathogenesis, but may also have therapeutic implications, e.g. by affecting the response to treatment with hypomethylating agents, which are known to promote DNA double strand breaks. [Display omitted] DisclosuresGattermann:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accomodation expenses, Research Funding.

Testicular germ cell tumor genomics.

Testicular germ cell tumors (TGCTs) are a model for curable cancer because of exquisite chemosensitivity and incorporation of multimodal therapy. Nevertheless, our ability to predict metastases in early-stage disease and responders to chemotherapy in advanced disease is limited. Treatment options for cisplatin-resistant disease are sparse. A further understanding of TGCT biology may allow for more precise patient counseling and identify novel therapies in patients with cisplatin-resistant disease. Adult TGCTs are characterized by frequent chromosomal anomalies and low rates of somatic mutations. Large-scale integrated molecular analysis of early-stage TGCT patients is actively underway. In addition to ubiquitous gain of isochromosome 12p, current molecular studies have confirmed mutations of previously described genes (i.e., KIT and KRAS) and described novel mutations. Analysis of cisplatin-resistant cases has identified high rates of alterations within the TP53-MDM2 axis and a high proportion of patients with potentially actionable targets, including TP53-MDM2, PI3 kinase, and MAPK signaling pathway alterations. The role of epigenetics in TGCT development and prognosis is also being further characterized. Further molecular characterization of TGCT may allow for avoidance of unnecessary treatment in patients with early-stage disease and also provide new treatment options in patients with cisplatin-resistant disease.

The Robustness of Midlatitude Weather Pattern Changes due to Arctic Sea Ice Loss

Abstract The significance and robustness of the link between Arctic sea ice loss and changes in midlatitude weather patterns is investigated through a series of model simulations from the Community Atmosphere Model, version 5.3, with systematically perturbed sea ice cover in the Arctic. Using a large ensemble of 10 sea ice scenarios and 550 simulations, it is found that prescribed Arctic sea ice anomalies produce statistically significant changes for certain metrics of the midlatitude circulation but not for others. Furthermore, the significant midlatitude circulation changes do not scale linearly with the sea ice anomalies and are not present in all scenarios, indicating that the remote atmospheric response to reduced Arctic sea ice can be statistically significant under certain conditions but is generally nonrobust. Shifts in the Northern Hemisphere polar jet stream and changes in the meridional extent of upper-level large-scale waves due to the sea ice perturbations are generally small and not clearly distinguished from intrinsic variability. Reduced Arctic sea ice may favor a circulation pattern that resembles the negative phase of the Arctic Oscillation and may increase the risk of cold outbreaks in eastern Asia by almost 50%, but this response is found in only half of the scenarios with negative sea ice anomalies. In eastern North America the frequency of extreme cold events decreases almost linearly with decreasing sea ice cover. This study’s finding of frequent significant anomalies without a robust linear response suggests interactions between variability and persistence in the coupled system, which may contribute to the lack of convergence among studies of Arctic influences on midlatitude circulation.

Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle.

ABSTRACTFragile X syndrome (FXS) is a disorder linked to the chromosome X long arm (Xq27.3), which is identified by a constriction named fragile site. It determines various changes, such as behavioral or emotional problems, learning difficulties, and intellectual disabilities. Craniofacial abnormalities such as elongated and narrow face, prominent forehead, broad nose, large and prominent ear pavilions, strabismus, and myopia are frequent characteristics. Regarding the oral aspects, deep and high-arched palate, mandibular prognathism, and malocclusion are also observed.Objective:The purpose of this study was to evaluate the dental radiographic characteristics as described in 40 records of patients with panoramic radiography.Material and Methods:The patients were in the range of 6–17 years old, and were divided into two groups (20 subjects who were compatible with the normality standard and 20 individuals diagnosed with the FXS), which were matched for gender and age. Analysis of the panoramic radiographic examination involved the evaluation of dental mineralization stage, mandibular angle size, and presence of dental anomalies in both deciduous and permanent dentitions.Results:The results of radiographic evaluation demonstrated that the chronology of tooth eruption of all third and second lower molars is anticipated in individuals with FXS (p<0.05). In this group, supernumerary deciduous teeth (2.83%), giroversion of permanent teeth (2.31%), and partial anodontia (1.82%) were the most frequent dental anomalies. In addition, an increase was observed in the mandibular angle size in the FXS group (p<0.05).Conclusion:We conclude that knowledge of dental radiographic changes is of great importance for dental surgeons to plan the treatment of these individuals.

Neurological Outcome in Fetuses with Mild and Moderate Ventriculomegaly.

Introduction Ventriculomegaly (VM) is one the most frequent anomalies detected on prenatal ultrasound. Magnetic resonance imaging (MRI) may enhance diagnostic accuracy and prediction of developmental outcome in newborns. Purpose The aim of this study was to assess the correlation between ultrasound and MRI in fetuses with isolated mild and moderate VM. The secondary aim was to report the neurodevelopmental outcome at 4 years of age. Methods Fetuses with a prenatal ultrasound (brain scan) diagnosis of VM were identified over a 4-year period. Ventriculomegaly was defined as an atrial width of 10-15 mm that was further divided as mild (10.1-12.0 mm) and moderate (12.1-15.0 mm). Fetuses with VM underwent antenatal as well as postnatal follow-ups by brain scan and MRI. Neurodevelopmental outcome was performed using the Griffiths Mental Development Scales and conducted, where indicated, until 4 years into the postnatal period. Results Sixty-two fetuses were identified. Ventriculomegaly was bilateral in 58% of cases. A stable dilatation was seen in 45% of cases, progression was seen in 13%, and regression of VM was seen in 4.5% respectively. Fetal MRI was performed in 54 fetuses and was concordant with brain scan findings in 85% of cases. Abnormal neurodevelopmental outcomes were seen in 9.6% of cases. Conclusion Fetuses in whom a progression of VM is seen are at a higher risk of developing an abnormal neurodevelopmental outcome. Although brain scan and MRI are substantially in agreement in defining the grade of ventricular dilatation, a low correlation was seen in the evaluation of VM associated with central nervous system (CNS) or non-CNS abnormalities.

Single centre experience on short bar technique for pectus excavatum.

Pectus excavatum (PE) is the most frequent anomaly of the anterior chest wall. Before 2001, all patients in Denmark were referred to the plastic and reconstructive surgeon for implantation of a subcutaneous silicone prosthesis, because the modified Ravitch procedure was not used. Since 2001, all patients have been treated with a modified Nuss procedure, which today has become the gold standard for correction of PE. From September 2001 to March 2016, 1,713 patients have been operated by a modified Nuss procedure using the short bar at Aarhus University Hospital with a male-female ratio 6:1. The median age was 16 years (range 7-58 years). All operations were done in general anesthesia with epidural analgesia and all patients were operated by the same surgeon. All patients were seen routinely 6 weeks after surgery and the bars were removed after 3 years. Patients were younger than 18 years in 1,109 cases (65%). The number of bars needed for optimal correction was one in 1,209 patients, two in 486 patients and three in 18 patients. The median length of bar changed from 11 inches to 10 inches during the study period. The annual number of procedures continued to rise during the study period [833 patients during the first 10 years and 880 patients in the last 6 years, though more patients received two bars in the later period, (34%) versus (24%)] and the proportion of patients older than 30 years increased from 7.7% to 10%. The average duration of the operation was 36 minutes (range 12-270 minutes) and did not change significantly during the study period, change in operation time which was around half an hour. The median postoperative hospital stay decreased over time from 6 to 2 days. There was no mortality. The modified Nuss procedure with the short bar technique is effective for the correction of PE. The results are stable with a low rate of bar malrotations, and in may most cases can be done in less than an hour in experienced hands.

Prevalence of Dental Anomalies in Permanent Dentition of Brazilian Individuals with Down Syndrome.

Objective:The aim of this study was to evaluate the incidence of dental anomalies in the permanent dentition of individuals with Down Syndrome (DS) to increase the knowledge on the dental issues in this syndrome. Method:One hundred and five panoramic X-rays of patients with DS (61 males and 44 females), aged 7 to 42 years were used. The data were statistically analyzed using bivariate analyses test (p <0.05). Results:Dental anomalies were observed in 50.47% of the sample. More than one anomaly was observed in 9.52% of the individuals. The most frequent dental anomalies were hypodontia and microdontia (16.19%), followed by retained tooth (10.47%), taurodontism (9.52%), supernumerary teeth (5.71%), macrodontia (2.85%) and root dilaceration (0.95%). There was no statistically significant difference between genders for any of the anomalies. Conclusion: A high prevalence of dental anomalies was observed in individuals with DS. The results of the present study reinforce the importance of good dental care, offering a greater basis for professionals who provide dental service to these patients.

Influence of skeletal class in the morphology of cervical vertebrae: A study using cone beam computed tomography.

To quantify the prevalence of cervical vertebrae anomalies and to analyze any association between them and skeletal malocclusions or head posture positions in the same study. Two hundred forty patients who were attending the Department of Orthodontics of the University of Valencia for orthodontic treatment were selected and divided into three groups: skeletal Class I (control group, 0° <ANB < 4°), Class II (ANB ≥ 4°), and Class III (ANB ≤ 0°) according to ANB Steiner angle. The morphology of the first five cervical vertebrae was analyzed with cone beam computed tomography to identify any anomalies. Intra- and interobserver error methods were calculated. Dehiscence and fusion of one unit (both 23.3%) and partial cleft (11.7%) were the most frequent anomalies, while occipitalization was the least common (3.3%). Dehiscence anomaly was observed when the control group was compared with Classes II and III and partial cleft anomaly when Class I was compared with Class III. Furthermore, NSBa and ss-N-sm/ANB angles were associated with partial cleft anomaly, while NSL/NL angle and extended head posture were associated with fusion anomaly. Fusion, dehiscence, and partial cleft were the most frequent cervical vertebrae anomalies. Dehiscence and partial cleft were found to present statistically significant differences between Class I and Classes II and III. Cervical vertebrae anomalies and head posture were associated with fusion.

Pulmonary hypoplasia: An analysis of cases over a 20-year period

Abstract Introduction Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. Material and methods A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. Results A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxaemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. Conclusions High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management.

Patent foramen ovale diagnosis: The importance of provocative maneuvers

Patent foramen ovale (PFO) is a frequent congenital anomaly, but massive right-to-left shunt (RTLS) is normally prevented by higher pressures in left heart chambers. However, mechanical ventilation with positive end-expiratory pressure (PEEP) can significantly increase right atrial pressure, accentuating the RTLS, mainly after major cardiothoracic surgery. We report a patient admitted to the intensive care unit after cardiac surgery. Pre- and intraoperative transesophageal echocardiography only described an aneurysmal interatrial septum with no shunt. However, high-PEEP ventilation induced a paradoxical response with life-threatening hypoxemia, triggering further echocardiographic evaluation, revealing massive RTLS across a stretch PFO. Provocative maneuvers (Valsalva/PEEP) significantly increase echocardiographic sensitivity, unmasking silent PFO. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:58-61, 2017.

Aplasia segmentar uterina em ovariosalpingohisterectomia eletiva em cadela – relato de caso

Congenital anomalies of the reproductive system of cats and dogs are rare. Among these, the unilateral agenesis of the uterine horn (unicornuate uterus) is the most frequent anomaly. Due to its rarity and few reports in literature, the aim of this work is to report the finding of uterine segment aplasia in a bitch during elective ovariohysterectomy. Traction of the right uterine horn was attempted after a retro umbilical celiotomy, disclosing a malformation characterized by shortening of the uterine horn, which measured 12 mm with the ovary close to the reduced segment. Malformation encountered during surgical procedures result in difficulties for the surgical team and prolonged surgical time, since other organs and systems can also present anomalies and require therefore careful inspection.

Dental characterization of colombian children with non syndromic cleft lip and palate

Introduction: When compared to general population, subjectsaffl icted with cleft lip and palate present alterations in craniofacial growth and development as well as high incidence of dental anomalies which vary according to studied population; agenesis, presence of supernumerary teeth, abnormal crown morphology and taurodontism can be counted amongst them. Objective: To assess prevalence of dental anomalies found in Colombian children with non syndromic cleft lip and palate sequels, being treated at health providing institutions. Methodology: A cross-sectioned descriptive, observational study was conducted on a sample of 258 medical histories and panoramic X-rays of Colombian childrentreated at different health providing institutions in the city of Bogota, Colombia. The sample was composed of 156/258 males (60.55%) and 102/258 (39.5%) females. Average age was 9.8 years (± 3.3 years). Results: Based on studied X-rays, it was determined that 38.4% (99/258) children presented full left unilateral cleft lip and palate sequels, 31.0% (80/258) exhibited bilateral cleft and 30.6% (79/258) suffered right unilateral cleft lip and palate. Most frequent dental anomalies found were; dental agenesis, supernumerary teeth and size anomalies. Prevalence for said anomalies were: dental agenesis, over 90%; supernumerary teeth: 40% and size anomalies: 30%. Conclusion: High prevalence of dental anomalies was found in children with cleft lip and palate in Bogota in concordance with information reported in scientifi c literature.

A Persistent Left-Sided Superior Vena Cava With Agenesis of the Right Superior Vena Cava in a Patient Who Underwent Liver Transplantation: A Case Report

The persistent left-sided superior vena cava (PLS-SVC) is the most frequent congenital anomaly of the mediastinal veins system. The concomitant agenesis of the right-sided superior vena cava (RS-SVC) is much less frequent. This variant is often discovered incidentally and could be mistaken for other findings or complicated intravascular accesses. A 29-year-old Caucasian woman presented with a decompensated autoimmune cirrhosis and hyperbilirubinemia. After a successful liver transplantation, a central venous catheter (CVC) was placed through the right jugular and a chest X-ray examination demonstrated its position into the left subclavian vein. After some days, it has been replaced by another CVC positioned from the left jugular vein. Using ultrasonography during the positioning maneuvers, we observed the metallic guide of the CVC in what seemed to be the dilated coronary sinus (CS). Subsequent chest X-ray examination demonstrated the catheter’s tip in the left paramediastinal position. In order to confirm the catheter’s exact position, we chose to inject contrast medium through the CVC under fluoroscopic guidance; the examination confirmed the presence of a PLS-SVC. These findings were also visible in a computed tomography (CT) examination previously performed in another hospital, which demonstrated the agenesis of the RS-SVC as well. We demonstrated a rare case of young patient with a PLS-SVC and agenesis of RS-SVC who underwent major surgery (liver transplantation) without any intra- or post-operative complications, even if advanced venous accesses with high flow catheters were used. J Med Cases. 2016;7(7):253-257 doi: http://dx.doi.org/10.14740/jmc2487w

Routine third trimester ultrasound in low risk pregnancy confers no benefit!: AGAINST: Arguments for a routine third trimester ultrasound: what the meta-analysis does not show!

The Cochrane meta-analysis on third trimester scanning, updated in June 2015, reached no new conclusions: ‘Based on existing evidence, routine late pregnancy ultrasound in low-risk or unselected populations does not confer benefit on mother or baby’ (Bricker et al. Cochrane Database Syst Rev 2015;6:CD001451). Most of the studies included in this meta-analysis, however, took place during the 1970s and 1980s. In the light of advances in ultrasound technologies and medical knowledge and practices, we can legitimately question the validity of the implementation of current pregnancy management based on the findings of these relatively old studies. This meta-analysis does not consider the detection rate of fetal anomalies to be a pertinent result. Nonetheless, it appears that routine late pregnancy ultrasound significantly increases this rate: the largest trial (Ewigman et al. N Engl J Med 1993;329:821–7) found that 50% of fetal anomalies are diagnosed during the third trimester. Some anomalies, such as congenital heart defects, can be missed at an earlier stage of pregnancy. When great vessel transposition, for example, is diagnosed during the third trimester, women can be referred to specialists during pregnancy and, finally, give birth in a specialised maternity unit prepared to provide optimal neonatal management, thus decreasing the risk of neonatal mortality (Khoshnood et al. Pediatrics 2005;115:95–101). Other rare critical anomalies, such as a vein of Galen aneurysmal malformation or microcephaly, are not detectable before the third trimester. Antenatal management can be adapted appropriately or, when allowed by law, women can choose a late termination of pregnancy in the most severe situations. Finally, the diagnosis of less severe but more frequent anomalies, such as hydronephrosis or megaureter, may improve, thus enabling increased monitoring during the baby's first months of life, which may sometimes prevent the onset of renal dysplasia. The Cochrane meta-analysis found that the risk of birthweight below the 10th percentile did not decrease among women having a routine third trimester ultrasound scan. Three of the four trials which utilised this outcome were published before 1993. All three studies failed to show a reduction in the incidence of intrauterine growth restriction (IUGR) with routine third trimester ultrasound screening. On the contrary, the most recent trial published by McKenna et al. in 2003 (McKenna et al. Obstet Gynecol 2003;101:626–32) found a significantly decreased risk of IUGR in the group of women who had routine third trimester ultrasounds. When IUGR is diagnosed, labour can be induced without increasing the risk of adverse outcomes (Boers et al. BMJ 2010;341:c7087). Studies have unfortunately been underpowered to estimate the impact of induction on the perinatal mortality rate among infants with IUGR. It is thus possible that ultrasound might decrease mortality in this population. Although meta-analyses are deemed to provide the highest level of evidence, they require detailed analysis from a clinical perspective, especially when they include very old trials. We consider that routine third trimester ultrasound confers benefit on babies and thus also on mothers and couples. In developed countries, where advanced ultrasound technology is widely available, there is no reason not to offer this examination routinely to all women. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Epidemiology and structure of congenital anomalies of the newborns in the region of Novi Sad (Vojvodina, Serbia) in 1996 and 2006.

According to the World Health Organization (WHO) definition, congenital anomalies are all disorders of the organs or tissues, regardless of whether they are visible at birth or manifest in life, and are registered in the International Classification of Diseases. The aim of this study was to compare the incidence and structure of prenatally detected and clinically manifested congenital anomalies in the newborns in the region of Novi Sad (Province of Vojvodina, Serbia) in the two distant years (1996 and 2006). This retrospective cohort study included all the children born at the Clinic for Gynecology and Obstetrics (Clinical Center of Vojvodina) in Novi Sad during 1996 and 2006. The incidence and the structure of congenital anomalies were analyzed. During 1996 there were 6,099 births and major congenital anomalies were found in 215 infants, representing 3.5%. In 2006 there were 6,628 births and major congenital anomalies were noted in 201 newborns, which is 3%. During 1996 there were more children with anomalies of musculoskeletal system, urogenital tract, with anomalies of the central nervous system and chromosomal abnormalities. During the year 2006 there were more children with cardiovascular anomalies, followed by urogenital anomalies, with significant decline in musculoskeletal anomalies. The distribution of the newborns with major congenital anomalies, regarding perinatal outcome, showed the difference between the studied years. In 2006 the increasing number of children required further investigation and treatment. There is no national registry of congenital anomalies in Serbia so the aim of this study was to enlight this topic. In the span of ten years, covering the period of the NATO campaign in Novi Sad and Serbia, the frequency of major congenital anomalies in the newborns was not increased. The most frequent anomalies observed during both years implied the musculosketelal, cardiovascular, urogenital and central nervous system. In the year 2006 there was a significant eruption of cardiovascular anomalies and a significant decrease of musculoskeletal anomalies, chromosomal abnormalities and central nervous system anomalies, while the number of urogenital anomalies declined compared to the year 1996.

Hipoplasia pulmonar: análisis de la casuística durante 20 años

IntroductionPulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. Material and methodsA retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. ResultsA total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. ConclusionsHigh neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management.

Comorbid Epilepsy and Developmental Disorders in Congenital Long QT SyndromeWith Life-Threatening PerinatalArrhythmias.

Given the association of long QT syndrome (LQTS) and neurological disorders, we speculated that the more severe LQTS phenotype, perinatal LQTS, would exhibit more frequent comorbid neurodevelopmental anomalies than LQTS without perinatal arrhythmias (nonperinatal LQTS). Congenital LQTS with life-threatening perinatal arrhythmias (perinatal LQTS) has a poor life prognosis. Twenty-one consecutive LQTS patients diagnosed before 1 year of age at our institution and 3 previously reported perinatal LQTS patients with neurological seizures were enrolled. In total, the clinical course was evaluated in 24patients. Among 21 infantile LQTS patients, 5 of 6 with perinatal LQTS (83%) were diagnosed with epilepsy and 4 (67%) with developmental disorders, but none with nonperinatal LQTS were. The total development quotient by Kinder Infant Development Scale scores was 17 to 72 (median 67) in 5 epileptic perinatal LQTS. Inthe 8 perinatal LQTS patients with neurological disorders, including 3 previously reported cases, epileptic seizures occurred at 2 days to 2.5 years of age and 5 had developmental disorders. Mutations in these 8patients were located in the transmembrane loop of KCNH2, and D3/S4-S5 linker, D4/S4, or the D4/S6 segment of SCN5A. A high comorbidity of neurodevelopmental anomalies was observed in perinatal LQTS. Mutations in patients with neurological comorbidities were in loci linked to LQTS with a severe cardiac phenotype. These observations indicate the possibility that neurological disorders in perinatal LQTS are manifested as neurological phenotypes associated with severe cardiac phenotypes, while we could not completely exclude another possibility that those were causedby a brain perfusion injury.

22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness - all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.

Minor anomalies in stillborn and second trimester miscarried fetuses.

In 1964, the landmark paper of Marden, Smith, and McDonald established that multiple minor anomalies in newborn infants are associated with an increased risk for major malformations. There were until now no comparable studies in stillbirths. The Wisconsin Stillbirth Service Program (WiSSP) has data regarding nearly 3,000 stillbirths and second trimester losses that have been analyzed for major anomalies and cause of death. One dysmorphologist retrospectively reviewed all 2,397 with usable photographs. Minor anomalies were identified in 1,413 (59%) with 575 of these (41%) having at least one major anomaly. Probability of a major anomaly increased from 7% with no minor anomalies to 15%, 36%, 67%, and 89% with 1, 2, 3, and >33 minor anomalies, respectively. Frequency of minor anomalies was less with lower resolution photographs, but did not show significant differences with maceration or gestational age. The most frequent minor anomalies were infraorbital creases/folds, lowset/posteriorly angulated ears, nuchal edema, flat face, equinovarus foot, camptodactyly, upslanted palpebral fissures, ear antihelix abnormalities (combined), micrognathia/retrognathia, and single transverse palmar crease. Except for infraorbital creases/folds each of these minor anomalies was strongly correlated with major anomalies (P < 0.0001). Infraorbital folds were the only anomaly which increased with placental cause of death, and reanalysis with placental causes excluded showed the expected relationship to major anomalies, suggesting that infraorbital folds may be markers for oligohydramnios due to various causes including placental hypoperfusion. Minor anomalies correlate with presence of major anomalies in stillborn fetuses, regardless of gestational age and maceration, and can provide information to guide decisions regarding laboratory testing and other evaluations.

Inferior vena cava anomalies and variations: imaging and rare clinical findings.

PurposeThe aim of this paper is to summarize imaging findings of some frequent and infrequent inferior vena cava (IVC) anomalies and variations.ConclusionsIVC anomalies should be suspected in patients presenting with pulmonary emboli, chronic pain, and deep vein thrombosis. To correctly characterize and classify IVC anomalies and variations is of crucial importance for proper planning of surgical interventions and thus for avoiding serious complications.Key Points• IVC anomalies should be suspected in patients with pulmonary emboli, pain, and venous thrombosis.• Awareness of IVC anomalies and variations is crucial for clinical and surgical procedures.• Unawareness of these anomalies may lead to severe and deadly complications.