Amniotic band syndrome and limb body wall complex in Europe 1980–2019

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019 and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980–2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly seen in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor.     

Prevalence of valproate syndrome in Europe from 2005 to 2014: A registry based multi-centre study

Women with epilepsy need to continue to take anticonvulsants during their pregnancies to prevent seizures from occurring. Since the 1980's, it has been known that the use of valproate (an anticonvulsant) in the first trimester of pregnancy is associated with an increased risk of spina bifida. Recent studies have also demonstrated increased risks of other congenital anomalies as well as a risk of cognitive impairment. Doctors in the EU are now advised not to prescribe valproate in pregnant women, in women who can become pregnant or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if there has been a reduction in the numbers of babies born with valproate syndrome in Europe from 2005 to 2014. Data from 15 European congenital anomaly registries, who are members of EUROCAT (A European network of population-based registries for the epidemiologic surveillance of congenital anomalies), identified 28 cases of valproate syndrome in 2.74 million births from 2005 to 2014. The prevalence of valproate syndrome in Europe significantly decreased from 0.22 per 10,000 births in 2005/6 to 0.03 per 10,000 births in 2013/14. One registry, Ile de la Reunion, had the majority of cases (17). After excluding these cases there still remained a decreasing trend even though it no longer reached statistical significance due to the small number of cases. This study emphasises the continued need for European collaboration in analysing rare exposures and rare anomalies.     

Epidemiology of achondroplasia: A population‐based study in Europe

Achondroplasia is a rare genetic disorder resulting in short‐limb skeletal dysplasia. We present the largest European population‐based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991–2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14–4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011–2015 vs. 36% in 1991–1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age – A EUROCAT study

Septo-optic nerve dysplasia is a rare congenital anomaly with optic nerve hypoplasia, pituitary hormone deficiencies and midline developmental defects of the brain. The clinical findings are visual impairment, hypopituitarism and developmental delays. The aim of this study was to report prevalence, associated anomalies, maternal age and other epidemiological factors from a large European population based network of congenital anomaly registries (EUROCAT). Data from 29 full member registries for the years 2005–2014 were included, covering 6.4 million births. There were 99 cases with a diagnosis of septo-optic dysplasia. The prevalence of septo-optic dysplasia in Europe was calculated to lie between 1.9 and 2.5 per 100,000 births after adjusting for potential under-reporting in some registries. The prevalence was highest in babies of mothers aged 20–24 years of age and was significantly higher in UK registries compared with other EUROCAT registries (P?=?0.021 in the multilevel model) and the additional risk for younger mothers was significantly greater in the UK compared to the rest of Europe (P?=?0.027). The majority of septo-optic dysplasia cases were classified as an isolated cerebral anomaly (N?=?76, 77%). Forty percent of diagnoses occurred in fetuses with a prenatal diagnosis. The anomaly may not be visible at birth, which is reflected in that 57% of the postnatal diagnoses occurred over 1 month after birth.This is the first population based study to describe the prevalence of septo-optic dysplasia in Europe. Septo-optic dysplasia shares epidemiological patterns with gastroschisis and this strengthens the hypothesis of vascular disruption being an aetiological factor for septo-optic dysplasia.     

The EuroBioBank Network: 10 years of hands-on experience of collaborative,transnational biobanking for rare diseases

The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding from the European Commission in 2002 (5th framework programme) and started operation in 2003. The set-up phase, during the EC funding period 2003–2006, established the basis for running the network; the following consolidation phase has seen the growth of the network through the joining of new partners, better network cohesion, improved coordination of activities, and the development of a quality-control system. During this phase the network participated in the EC-funded TREAT-NMD programme and was involved in planning of the European Biobanking and Biomolecular Resources Research Infrastructure. Recently, EBB became a partner of RD-Connect, an FP7 EU programme aimed at linking RD biobanks, registries, and bioinformatics data. Within RD-Connect, EBB contributes expertise, promotes high professional standards, and best practices in RD biobanking, is implementing integration with RD patient registries and ‘omics'' data, thus challenging the fragmentation of international cooperation on the field.     

Descriptive epidemiology of isolated anal anomalies: A survey of 4.6 million births in Europe

The prevalence of anal anomalies among 4,618,840 births recorded in 33 EUROCAT registries between 1980 and 1994 was 4.05 per 10,000 births. Of the 1,846 recorded cases, 672 (36.4%) were isolated anal anomalies while 1,174 (63.6%) occurred together with other anomalies. Only isolated anal anomalies were analyzed in this study: 75.5% were atresias, 10.1% of which were above and 89.9% were below the level of the levator ani muscle. Fistula occurred in 53% of supralevator and 37% of infralevator atresia. Other anal anomalies were ectopic anus (3.4%), congenital anal fistula (14.7%), and persistent cloaca (0.9%). There was a predominance of males in anal atresia without fistula (male to female (M:F) ratio was 6.7 for supralevator and 2.3 for infralevator atresia), but no significant sex difference in atresias with fistula. There was a predominance of females in ectopic anus and congenital anal fistula (M:F = 0.11 and 0.36 respectively). High frequencies of fetal deaths were recorded in supralevator atresia without fistula (8.3%) and in persistent cloaca (11.1%). Mean gestational length and mean birth weights were reduced for persistent cloaca but were within normal limits for other isolated anal anomalies. Odds ratios (ORs) for mothers above 35 years were increased for supralevator atresia without fistula, supralevator atresia with fistula, and congenital anal fistula. ORs for mothers below 30 years were slightly increased for supralevator atresia without fistula and decreased for persistent cloaca. There were marked differences in prevalence and distribution of anal anomalies among the EUROCAT registries. The results indicated that there are epidemiological differences among the various types of anal anomalies which might reflect different embryological origins. © 2001 Wiley‐Liss, Inc.     

Descriptive epidemiology of isolated anal anomalies: a survey of 4.6 million births in Europe.

The prevalence of anal anomalies among 4,618,840 births recorded in 33 EUROCAT registries between 1980 and 1994 was 4.05 per 10,000 births. Of the 1,846 recorded cases, 672 (36.4%) were isolated anal anomalies while 1,174 (63.6%) occurred together with other anomalies. Only isolated anal anomalies were analyzed in this study: 75.5% were atresias, 10.1% of which were above and 89.9% were below the level of the levator ani muscle. Fistula occurred in 53% of supralevator and 37% of infralevator atresia. Other anal anomalies were ectopic anus (3.4%), congenital anal fistula (14.7%), and persistent cloaca (0.9%). There was a predominance of males in anal atresia without fistula (male to female (M:F) ratio was 6.7 for supralevator and 2.3 for infralevator atresia), but no significant sex difference in atresias with fistula. There was a predominance of females in ectopic anus and congenital anal fistula (M:F = 0.11 and 0.36 respectively). High frequencies of fetal deaths were recorded in supralevator atresia without fistula (8.3%) and in persistent cloaca (11.1%). Mean gestational length and mean birth weights were reduced for persistent cloaca but were within normal limits for other isolated anal anomalies. Odds ratios (ORs) for mothers above 35 years were increased for supralevator atresia without fistula, supralevator atresia with fistula, and congenital anal fistula. ORs for mothers below 30 years were slightly increased for supralevator atresia without fistula and decreased for persistent cloaca. There were marked differences in prevalence and distribution of anal anomalies among the EUROCAT registries. The results indicated that there are epidemiological differences among the various types of anal anomalies which might reflect different embryological origins.     

Meckel–Gruber Syndrome: a population-based study on prevalence,prenatal diagnosis,clinical features,and survival in Europe

Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.     

How the EUCERD Joint Action supported initiatives on Rare Diseases

Joint Actions are successful initiatives from the European Commission (EC) that have helped to raise awareness and to bring significant benefit to those suffering from a rare disease (RD). In this paper, we will focus on the activities developed by the EUCERD Joint Action (EJA) and by the Orphanet Joint Action (“Orphanet Europe”). EUCERD Joint Action was co-funded by the EC and the Member States between 2012 and 2015 to help to define the activities and policies in the field of RD and foster exchange of experiences amongst Member States. This project is the continuation of previous efforts to turn RD a priority in the EC Health Programmes. “Orphanet Europe” was a Joint Action co-funded by INSERM, the French Directorate General for Health and the EC to address the need for a common portal that would gather the most update information regarding RD. This need was identified in the European Commission report “Rare Diseases: Europe's challenge” and in the Recommendation of the Council for a European RD portal. These joint actions have supported the policy development work of the European Commission, through the support of their committees for rare diseases. In this paper, the authors aim to raise awareness of the work done by the EUCERD Joint Action on behalf of the rare disease community and the policies established.     

Mosquito-borne disease surveillance by the European Centre for Disease Prevention and Control

For a few years, a series of traditionally tropical mosquito-borne diseases, such as chikungunya fever and dengue, have posed challenges to national public health authorities in the European region. Other diseases have re-emerged, e.g. malaria in Greece, or spread to other countries, e.g. West Nile fever. These diseases are reportable within the European Union (EU), and the European Centre for Disease Prevention and Control collects information in various ways to provide EU member states with topical assessments of disease threats, risks and trends for prompt and appropriate public health action. Using disease-specific expert networks, the European Surveillance System (TESSy) collects standardized comparable information on all statutory communicable diseases in a database. In addition, the event-based surveillance aims to detect potential public health threats early, and to allow timely response and support to blood deferral decisions for pathogens that can be transmitted through blood donation. Laboratory capacity for early detection is implemented through external quality assessments. Other activities include the development of guidelines for the surveillance of mosquito vectors, and the production of regularly updated maps on the currently known occurrence of mosquito vector species.     

Descriptive epidemiology of Cornelia de Lange syndrome in Europe

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed 相似文献   

Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15

BackgroundHepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies.StudyCountries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases.ResultsSurveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs.ConclusionDiscussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the ‘One Health’ approach to better informing on human exposure to HEV.     

Prenatal detection of rare chromosomal autosomal abnormalities in Europe

The aim of the present study was to evaluate the prenatal detection of rare chromosomal autosomal abnormalities by ultrasound (US) examination. Data were obtained from 19 congenital malformation registries from 11 European countries, between 01/07/96 and 31/12/98. A total of 664,340 births were covered and 7,758 cases with congenital malformations were recorded. Rare autosomal abnormalities were diagnosed in 114 cases (6.6%) from a total of 1,738 chromosome abnormalities. There were a wide variety of autosomal abnormalities: the most common were deletions (33 cases), duplications (32 cases), trisomies of chromosomes 8, 9, 10, 14, 15, and 16 (23 cases), and unbalanced rearrangements (19 cases). Out of these cases, 45.6% were detected prenatally by US examination due to the presence of congenital anomaly. As for the types of chromosomal anomaly, unbalanced rearrangements and deletions were the most frequently detected by US. A high percentage of cases with balanced rearrangements were associated with severe congenital anomalies. The most frequent congenital anomalies detected by US were cystic hygroma (20.6%), central nervous system defects (17.6%), cardiac defects (13.2%), and diaphragm defects (10.3%). This large series offers useful information about prenatal diagnosis by US of congenital defects associated with rare autosomal abnormalities and it provides a valuable knowledge about outcome. Fetal anomalies detected by US that were associated with rare autosomal abnormalities were significantly more frequent than those associated with common chromosomal abnormalities (45.6 vs. 34.7%). This study indicates the need to increase the detection of congenital anomalies by US.     

Changing trend in congenital abdominal wall defects in eastern region of Ireland

In the past six years, there have been reports from abroad of an unexplained rise in the birth prevalence rate of the congenital abdominal wall defect gastroschisis, while rates for the macroscopically similar anomaly omphalocoele have remained stable. The Dublin EUROCAT Registry of congenital anomalies monitors trends in the birth prevalence of birth defects in the eastern region of Ireland. We analysed births of children with omphalocoele and gastroschisis born in the period 1981-2000, with comparisons of a number of demographic and obstetric variables. During the 20 year period the birth prevalence rate for omphalocoele remained stable at 2.5/10,000 births, whereas the rate for gastroschisis increased significantly during the 1990s from 1.0/10,000 in 1991 to 4.9/10,000 in 2000. Most of the increase occurred among mothers under 25 years of age. Omphalocoele was associated with a relatively high proportion of other major congenital anomalies. This study showed that there has been an unexpected rise in the birth prevalence of gastroschisis in the region, similar to that experienced in other countries in the same time period and likely to have common aetiological features.     

The evaluation of the germinal mutagenic impact of Chernobyl radiological contamination in Hungary.

The genetic consequences of radioactive fall-out deposition from the Chernobyl (USSR) accident in Hungary was evaluated as a part of the ongoing programme on the population-based Hungarian Surveillance of Germinal Mutations. The surveillance is based on three groups of indicator conditions: 15 sentinel anomalies (indicators of germinal dominant gene mutations), Down's syndrome (an indicator of germinal numerical and structural chromosomal mutations) and unidentified multiple congenital abnormalities (indicators of germinal dominant gene and chromosomal mutations). Cases with these indicator conditions were selected from the material of the Hungarian Congenital Abnormality Registry. After the diagnostic accuracies were checked, familial and sporadic cases were separated. Only the latter group was evaluated for evidence of new mutations. The analysis did not reveal any measurable germinal mutagenic effects of the Chernobyl accident. Furthermore, there were no significant differences in the rates of these three groups of indicator conditions between regions with higher and lower increased background radiation.     

Congenital defects of the limbs in stillbirths: Data from a population-based study

We analyzed limb deficiencies occurring in stillbirths with congenital anomalies registered in the Health Surveillance Registry of British Columbia between the years 1964 and 1984. Thirty stillborn infants presenting with various defects of the limbs were found during this time, giving an incidence of 39.52 in 10,000 stillbirth (1:253). This incidence is significantly higher than the incidence among liveborn individuals in the Province (5.97 in 10,000 livebirths or 1:1,842). Most cases involved the upper limbs, and most frequently the radius. Additional anomalies were present in 77% of cases, compared to 48% in liveborns. The study of stillbirth with congenital anomalies provides important information regarding the spectrum of birth defects seen in this group. This may be of relevance because of improved survival possibilities due to advances in perinatal care. © 1993 Wiley-Liss., Inc. © 1993 Wiley-Liss, Inc.     

Integrated Image Data and Medical Record Management for Rare Disease Registries. A General Framework and its Instantiation to the German Calciphylaxis Registry

Especially for investigator-initiated research at universities and academic institutions, Internet-based rare disease registries (RDR) are required that integrate electronic data capture (EDC) with automatic image analysis or manual image annotation. We propose a modular framework merging alpha-numerical and binary data capture. In concordance with the Office of Rare Diseases Research recommendations, a requirement analysis was performed based on several RDR databases currently hosted at Uniklinik RWTH Aachen, Germany. With respect to the study management tool that is already successfully operating at the Clinical Trial Center Aachen, the Google Web Toolkit was chosen with Hibernate and Gilead connecting a MySQL database management system. Image and signal data integration and processing is supported by Apache Commons FileUpload-Library and ImageJ-based Java code, respectively. As a proof of concept, the framework is instantiated to the German Calciphylaxis Registry. The framework is composed of five mandatory core modules: (1) Data Core, (2) EDC, (3) Access Control, (4) Audit Trail, and (5) Terminology as well as six optional modules: (6) Binary Large Object (BLOB), (7) BLOB Analysis, (8) Standard Operation Procedure, (9) Communication, (10) Pseudonymization, and (11) Biorepository. Modules 1–7 are implemented in the German Calciphylaxis Registry. The proposed RDR framework is easily instantiated and directly integrates image management and analysis. As open source software, it may assist improved data collection and analysis of rare diseases in near future.     

Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000–2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71–2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46–0.64), 1.04 (95% CI 0.92–1.17) and 0.30 (95% CI 0.24–0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19–5.36 per 1000), proportion prenatally diagnosed (50–100%) and proportion of prenatally diagnosed resulting in TOPFA (13–67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors.     

Prevalence,prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.