Boletín del ECEMC: Revista de Dismorfología y Epidemiología - 2009 - Serie V Nº 8
http://hdl.handle.net/20.500.12105/5713
2024-03-29T09:32:11ZBoletín del ECEMC: Revista de Dismorfología y Epidemiología 2009; Serie V Nº 8
http://hdl.handle.net/20.500.12105/14063
Sumario de Boletín del ECEMC: Revista de Dismorfología y Epidemiología 2009; Serie V Nº 8
2009-10-01T00:00:00ZBoletín del ECEMC: Revista de Dismorfología y Epidemiología - 2009 - Serie V Nº 8
http://hdl.handle.net/20.500.12105/14062
Número completo de: Boletín del ECEMC: Revista de Dismorfología y Epidemiología - 2009 - Serie V Nº 8
2009-10-01T00:00:00ZGripe A (H1N1) en Mujeres Embarazadas: Hechos Conocidos, Desconocidos, y Evaluación Beneficios-Riesgos
http://hdl.handle.net/20.500.12105/14061
2009-10-01T00:00:00ZSíndrome de Aicardi-Goutieres de presentación neonatal simulando infección congénita
http://hdl.handle.net/20.500.12105/14060
Aicardi-Goutières Syndrome (AGS) is a genetic disorder with autosomal recessive aetiology characterized by an early developed encephalopathy with severe physical and mental handicaps. The neonatal form (20% of the cases) shows a phenotype similar to a congenital infection, hence there exists the possibility of misdiagnosis and misinformation to parents about the risk of recurrence. We present a new case of AGS with a neonatal onset and also review clinical patterns, laboratory and neuroimaging findings, and new advances in geneticmolecular diagnosis that have allowed us to delineate the phenotypic spectrum and confirm the aetiology in more than 80% of cases.
2009-10-01T00:00:00ZSíndrome de Mowat-Wilson con una deleción en el gen ZEB2 no descrita previamente
http://hdl.handle.net/20.500.12105/14059
Mowat-Wilson syndrome –MWS- (MIM 235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 (Zinc finger E-box-binding homeobox 2 gene) gene, that codifies the SIP1 (Smad interacting protein 1) localized within the 2q22-q23 chromosomal region. It conforms a syndrome of multiple congenital anomalies, characterized by a typical facial phenotype, moderate to severe mental retardation, epilepsy and different congenital malformations including Hirschsprung disease, congenital cardiopathy, agenesis of the corpus callosum, genitourinary and eye anomalies. We present a patient suffering MWS with a heterozigotic deletion of a base in the 461 position of the codifying sequence for the ZFB2 gene, corresponding to the codon 157, which alters the reading frame and causes the appearance of a stopping codon, 17 positions later. Genotype: c.461 delA (p.Glu157GlufsX17)/normal. This mutation does not appear described in the literature but its presence justifies the reported clinical manifestations. The genetic studies performed to the parents were normal, confirming a de novo mutation.
2009-10-01T00:00:00ZSituación actual en España sobre el diagnóstico etiológico en fetos procedentes de abortos por defectos congénitos. Directrices para un protocolo mínimo
http://hdl.handle.net/20.500.12105/14058
Since the passing of the Spanish law permitting termination of pregnancy (ToP) after the detection of foetal anomalies, in July 1985, the ECEMC has undertaken the commitment to register the maximum information regarding the cases of ToP due to congenital anomalies. This interest is not only prompted by the need of a proper surveillance of these pathologies, what is important for public health purposes, but also for getting an etiologic diagnosis for each case; although this is only possible by retrieving minimum clinical and non-clinical information, depending on each case. This is important, because not achieving an etiologic diagnosis implies not being able to provide the family with information regarding recurrence risk, the risk for possible carriers among their healthy children, and for future pregnancies, planning prenatal diagnosis, and pre-implantation diagnosis or assisted reproduction for certain pathologies. At present, in Spain, there is no official protocol for the study of foetuses from ToP with congenital anomalies, what precludes from getting prevention in all their different levels, starting by the possibility of having a correct diagnosis. To cover that need, and based on the experience of the ECEMC, we highlight a small protocol with the minimal data to be collected to increase the possibilities to reach to a proper diagnosis, and, therefore, provide the parents with complete information. From the point of view of the health practice, this is the correct way, not only for getting the diagnosis, but because this is the only way to also help to diminish the awful situation of couples undergoing ToP due to foetal malformations.
2009-10-01T00:00:00ZAnálisis clínico de los recién nacidos con defectos congénitos registrados en el ECEMC: Distribución por etiología y por grupos étnicos
http://hdl.handle.net/20.500.12105/14057
In this chapter, the information gathered by ECEMC between January 1980 and December 2008 has been analysed. It corresponds to 2,463,134 consecutive newborn infants surveyed, among which 37,545 (1.52%) presented congenital defects detected during the first 3 days of life. When these were distributed by clinical presentation, all the groups showed a statistically significant diminishing trend since the base period, mainly attributable to the impact of termination of pregnancy after the diagnosis of foetal alterations. The distribution by clinical presentation was specifically analysed for 17 congenital defects which are usually monitored, this information being useful in the field of prenatal diagnosis. Blastogenic defects showed a statistically significant decrease in the study period, except in the last 6 years, which could be due to the influence of the immigrant population. All the infants registered were distributed by the causes of the defects, and those with syndromes were also distributed by etiology and frequency in the ECEMC data. Moreover, all infants with congenital defects were distributed by the organic system or area affected, and presented in 3 periods of time. Given the increase in the immigrant population in our country, the distribution of all infants with congenital defects by ethnic group is shown, with whites being distinguished as native or foreigner. This distribution by ethnic group is important for designing specific campaigns for prevention, education and information, according to their real needs. When analysing some selected defects in those groups, with respect to the group of native whites, a lower percentage of cases with neural tube defects was found among blacks; a higher percentage of cases with cardiovascular defects was registered among blacks, gipsies and arabs; a lower percentage of cases with hypospadias was observed among blacks and indoamericans, and a higher percentage of cases with postaxial polydactyly was found among blacks. This data provides useful information for identifying defects for which the gene frequencies of the native population could be modified by immigration, as well as to define specific needs of the different ethnic groups in Spain.
2009-10-01T00:00:00ZPaciente con Síndrome de Cri-Du-Chat y de Beckwith-Wiedemann originado por un derivado de translocación paterna
http://hdl.handle.net/20.500.12105/14056
Cri-du-Chat syndrome (CdCS) is one of the most common deletion syndromes (1/15,000-1/50,000 live births) caused by the loss of material from the short arm of chromosome 5 (5p). Although the breakpoints are variable, the CdCS critical region has been shown to be located at 5p15.2 as microdeletions of this region as well as larger deletions of varying sizes, produce the phenotype associated with this syndrome. Patients born with CdCS usually present with microcephaly, round face, hypertelorism, epicanthic folds, micrognathia, large nasal bridge, growth delay, and severe psychomotor retardation. However, the main distinguishing feature of this syndrome is the characteristic cry: a high-pitched, monotonous, cat-like cry. Approximately 80% of patients with CdCS have “de novo” deletions, 10% present with a derivative chromosome from a parental translocation that results in monosomy 5p with trisomy of the other chromosome involved in the rearrangement, and 10% are caused by rarer chromosome alterations, such as inversions. The second disorder of interest, Beckwith-Wiedemann syndrome (BWS), has a frequency of 1 in 13,700 live born children and is the most common of the overgrowth syndromes. It is characterised by macrosomia, hemihyperplasia, macroglossia, abdominal wall defects (omphalocele, umbilical hernia, diastasis recti), earlobe creases, visceromegaly, neonatal hypoglycemia, and a predisposition to embryonal malignancies such as hepatoblastoma, neuroblastoma, rabdomyosarcoma, and Wilms tumour. The etiology of BWS is very complex, involving genetic and epigenetic processes within the p15 region in the short arm of chromosome 11. Up to 60 % of patients with BWS have an epigenetic error in one of the imprinting centers in 11p15 (caused by loss or gain of methylation), approximately 20% have uniparental disomy (UPD), 10% have mutations of the CDKN1C gene, and only 2% of cases have chromosome rearrangements affecting 11p. The majority of these alterations result from the unbalanced segregation of a parental translocation or inversion, and when the disorder is caused by the inheritance of a balanced rearrangement, the alteration is always maternallyderived. To assess the recurrence risk, it is very important to identify the type of mechanism causing the syndrome, although in 10-15% patients the etiology for BWS remains unidentified. In this article, we present a newborn female with a derivative chromosome 5, resulting from a paternal translocation involving chromosomes 5 and 11. This has resulted in the proband having partial monosomy for 5p and partial trisomy for 11p, producing a clinical picture in which the features of both CdCS and BWS are observed. The baby presented with a strange cry, dysmorphics features, (including epicanthic folds, long palpebral fissures, broad nasal bridge with small nose, and microretrognathia), macroglossia, short neck, bell-shaped thorax with widely-spaced, asymmetrical nipples, single-palmar crease on both hands, long feet with malposition of the toes, and interiorly displaced anus. She also showed generalized hypotonia and neonatal persistent hypoglycemia. Although high-resolution G-banded chromosome studies showed an apparently normal, female karyotype, a FISH screening of the subtelomeric regions of all chromosomes showed monosomy for 5p and trisomy for 11p. Further FISH investigation with a probe specific for the CdCS critical region confirmed this locus to be deleted. Parental studies detected the presence of an apparently balanced translocation between chromosomes 5 and 11 in the father. Molecular analysis using microsatelites was carried out showing a deletion of 15.93 Megabases (Mb) on chromosome 5 and a deletion of 10.87 Mb on chromosome 11, both of paternal origin. Although there are six previous published cases that originated from similar paternal translocations, the altered chromosome regions are of different sizes, and the current infant seems to be the first in which the clinical characteristics of both CdCS and BWS are recognized.
2009-10-01T00:00:00ZReordenamientos cromosómicos complejos (CCRs): Presentación de un nuevo caso con 5 puntos de rotura entre los cromosomas 4 y 8.
http://hdl.handle.net/20.500.12105/14055
Complex chromosomal rearrangements (CCRs) were first defined by Pai et al. (1980) as "structural chromosomal rearrangements with at least three breakpoints and the exchange of genetic material between two or more chromosomes”. More recently, in 2003, Houge et al. redefined CCRs as "constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints”, which has become the definition more commonly used nowadays when referring to CCRs. In general, due to the intrinsic complexity involved in their formation, CCRs are rare. However, over the years, CCRs have been classified by various authors taking into account different criteria. Therefore, they may be classified according to their transmission (either “inherited” or “de novo”), the number of breakpoints involved (“four or less” and “more than four”), and their structure, for which three types can be distinguished: a) three-way exchange CCRs, b) exceptional CCRs and c) double two-way exchange CCRs. Usually the CCRs have deletions and duplications associated, which are not easily detected unless high-resolution cytogenetic analysis is applied. However, it is the application of this technique, together with the use of the latest molecular tools, such as array-CGH (array-Comparative Genomic Hybridization), that will allow the proper characterization of the possible rearrangements in each CCR. These new technologies will also reveal the genes that have been deleted or duplicated in the CCRs, so that in some cases it may be possible to postulate the mechanism of formation of the CCR and therefore to know the prognosis and/or evolution of patients with a CCR. This article describes a patient, with growth retardation, developmental delay, nystagmus, microcephaly and micrognathia, in which high-resolution G-banded chromosome analysis together with fluorescence in situ hybridisation (FISH) and molecular techniques revealed the presence of an “exceptional”, de novo CCR, with five breakpoints and two deleted regions, involving chromosomes 4 and 8. In addition, a review of the genes located in the deleted regions and their correlation with the patient’s phenotype will be presented.
2009-10-01T00:00:00ZVigilancia epidemiológica de anomalías congénitas en España: Análisis de los datos del registro del ECEMC en el período 1980-2008
http://hdl.handle.net/20.500.12105/14054
The Spanish Collaborative Study of Congenital Malformations (ECEMC) is a programme for research on congenital anomalies. It was created in 1976 by Prof. Martínez-Frías, as a hospital-based, case-control registry of newborn infants in Spain. Since its foundation, it has surveyed a total population of more than 2.6 million births, and studied more than 39,900 consecutive infants with congenital anomalies. According to the most recent data, the coverage of the registry reaches 21.55% of total births in Spain. The global frequency of infants with congenital defects has significantly decreased along the time, from 2.22% in the base period (1980-1985), to 1.03% in 2008. This significant decrease is mainly attributable to the impact of prenatal diagnosis and further interruption of some affected pregnancies, which is legal in Spain since 1985. Such a decrease has been observed in most of the Spanish Autonomic Regions (see Fig. 1) and participating hospitals, being statistically significant in many of them. The only Autonomic Region in which an increase was detected is Extremadura, where the base frequency was quite low due to a small coverage of births, in a period during which the most complicated pregnancies, and infants with serious birth defects, had to be referred to other regions (a situation that has changed since the basal period). From the periodic analysis of the frequency of a group of 33 defects selected due to their relatively high base frequency or morbidity/mortality that they bear, only the heart/great vessels defects, and unilateral renal agenesis, have increased along the time, possibly as a result of increasing facilities for their diagnosis. The temporal-spatial analyses mostly detected decreases in the frequency of many of the defects studied in several Spanish Autonomic Regions. However, there were also some increases. Specifically, in the frequency of anophthalmia/microphthalmia in the Región de Murcia, cleft palate in Aragón, oesophageal atresia/stenosis in Galicia, and anal-rectal atresia/stenosis in Canarias. Regarding anophthalmia/microphthalmia in the Región de Murcia, after excluding one case with a chromosomal abnormality and another one with familial Waardenburg syndrome, the increase lost its statistical significance, and apparently there was not any common denominator among the other cases registered, apart from the area of birth. With respect to the increase of oesophageal atresia/stenosis in Galicia, this was due to the birth of 4 cases in 2008, without any known common characteristic from which a causal relationship could be inferred. This defect will be subject to a special surveillance during the next months. Concerning the increase of cleft palate in Aragón, there was not any sign of a common cause restricted to this geographical area either. The last increase was based on the birth of 3 clinically different cases with anal atresia in Canarias, and no causal agent could be specifically linked to this area. From this report, it is clear the crucial role of the ECEMC system in the epidemiological surveillance of congenital anomalies in Spain, given its long experience since 1976, its huge database, the network of hospitals established, and the close and dynamic collaboration between its participants. This has enabled not only to calculate the birth frequency of congenital defects in Spain on a consecutive series on non-selected newborn infants, in a live and active system, but also to study their evolution along the time, and their geographical distribution, as well as their clinical diagnosis.
2009-10-01T00:00:00ZCaracterísticas de las madres que siguieron técnicas de reproducción asistida
http://hdl.handle.net/20.500.12105/14053
Background: Assisted reproductive technologies (ART), such as in vitro fertilization, intracytoplasmic sperm injection (ICSI), assisted fecundation, and all the fertility treatments and procedures, have been successfully used to overcome infertility. Indeed, it has been estimated that between 1 and 4% of births in developed countries are conceived trough ART. But at the same time, rising concerns exist on their potential adverse effects on the embryo and fetal development. However, in spite of the huge amount of studies that have been published, big gaps in this knowledge still exist. To assess this association through epidemiological studies, it is necessary to recognize which maternal characteristics, among others, could confound the results. However, some of the maternal characteristics may be related with cultural and social aspects, as well as with other local influences. Therefore, it is advisable to identify those characteristics in the different populations. Objective and methods: Here we present the results of the analysis of several maternal characteristics on data from the cases and controls mothers of the ECEMC database. The analysis included 20,233 mothers of consecutive live born infants with congenital defects, and 19,411 mothers of control infants. The studied characteristics were: maternal age ( 19, 20-30, 31-35, 36), level of education (primary, secondary, and university studies), body mass index (BMI) in three strata (<25, 25-30, >30), maternal chronic diseases, maternal diabetes mellitus, hypertension, gestational diabetes, infectious diseases during pregnancy, tobacco and alcohol consumption while pregnant, multiple births, and caesarean section. Due to the number of analyses performed, the statistical significance was established in p<0.01. Results: We have observed that women undergoing ART are older, with higher educational levels, suffer more chronic diseases, higher frequency of gestational diabetes, and more infectious diseases than mothers with natural conceptions. Most of these results are observed either in cases´ mothers or controls´ mothers, but did no differ when we analyzed cases versus controls´ mothers, all of them using ART for conception. On the other hand, mothers following ART, are less smokers, do not have more frequency of both diabetes mellitus and hypertension. Regarding the BMI, the only statistically significant result is an increased frequency of women having a BMI of <25 among those following ART. Conclusions: Many of the studied characteristics can be confounder factors for epidemiological analyses to identify potential risks of ART to produce birth defects. In addition, although most of the results are similar to those observed in other studies, particularly in Sweden, some of the observed differences may be due to variations in social and educational aspects. Therefore, it is advisable to identify which maternal characteristics can be confounder factors in each population.
2009-10-01T00:00:00ZFármacos antipsicóticos y embarazo: resumen de la literatura y experiencia en el ECEMC
http://hdl.handle.net/20.500.12105/14052
The antipsychotic drugs are medications about which a considerable number of telephone calls are received in our teratology information services (SITTE and SITE). We present a review of the literature about the use of this group of drugs during pregnancy. On the other hand, in order to assess the experience in the CIAC, we have studied the intake of antipsychotics in the ECEMC and the queries made on these medications to both teratology information services. Our results show that the intake of antipsychotics during pregnancy is low. However, the number of queries about this type of drugs is increasing, both in the SITTE and in the SITE, probably because of the concern they generate due to the lack of clear information about their use during pregnancy.
2009-10-01T00:00:00ZActividad de los servicios de información sobre teratógenos (SITTE y SITE) durante el año 2008.
http://hdl.handle.net/20.500.12105/14051
We summarize the activity of the two Teratology Information Services: SITTE (for health professionals) and SITE (for the general population), during 2008. The total number of calls received in both services was 4,910 (943 from SITTE and 3,967 from SITE). This number has increased compared to previous year. The main users of the SITTE (gynecologists 54.96%) and the SITE (pregnant women 79.89%), have asked preponderantly about the use of drugs (70.22% of the SITTE and 37.49% of the SITE phone calls), during ongoing pregnancies at the moment they were calling (82.82% in the SITTE and 85.18% in the SITE). Additionally, we analyze the type of consulted factors and some characteristics of the users to orientate our work more effectively to the actual demand.
2009-10-01T00:00:00ZResúmenes de los Pósters presentados en la XXXII Reunión del ECEMC
http://hdl.handle.net/20.500.12105/14050
2009-10-01T00:00:00ZComentario editorial: el lado “perverso” del factor de impacto en la investigación biomédica en nuestro país
http://hdl.handle.net/20.500.12105/14049
2009-10-01T00:00:00ZEl análisis cienciométrico de las publicaciones biomédicas sobre genética y dismorfología clínica
http://hdl.handle.net/20.500.12105/14048
Genetic and dysmorphology sciences form a multidisciplinary field that produces a wide range of scientific journals. The aim of this study was to perform a scientometric analysis of genetic science journals in Journal Citation Reports-Science Citation Index. Methodology: we study the three areas dedicated to genetic sciences (Genetics & Heredity, Develpmental Biology and Toxicology) in the 2007 JCR-SCI edition. Bibliometric indicators used are: journals, articles, citations, impact factor (IF), immediacy index, half life and journals with the greatest IF in each speciality. We also perform a special analysis about publications of ECEMC working group in JCR-SCI. Results: in the area of Genetics & Heredity we found a total of 132 journals, 16,059 articles, 675,463 citations and an average IF of 2,595, the greatest IF belonging to Nat Genet (25,556) and Nat Rev Genet (22,399). The area of Develpmental Biology contains 37 journals, 3,749 articles, 199.213 citations and an average IF of 2,688, the greatest IF belonging to Annu Rev Cell Dev Bio (23,545) and Gene Dev (114,795). The area of Toxicology contains 73 journals, 7,874 articles, 193,395 citations and an average IF of 1,942, the greatest IF belonging to Annu Rev Pharmacol (21,696) and Crit Rev Toxicol (5,145). ECEMC working group has 111 articles in JCR published in the last 10 years, mainly in the area of Genetics & Heredity and in journals with IF 2 . Conclusions: we found out a broad representation of journals in the field of genetic and dysmorphology from the 6,426 journals included in the 2007 JCR-SCI edition. Bibliometric characteristics differ in accordance to nature of the three areas. The contribution of ECEMC working group is important in number and quality of publications in this database. Due to significant limitations observed in the IF, we suggest conducting its analysis from a multidimensional bibliometric perspective, and always within its contextual research area.
2009-10-01T00:00:00Z