Anomalía de Möebius y el concepto de secuencia malformativa: Importancia del conocimiento y uso adecuado de la terminología

Dismorfología, Citogenética y Clínica: Resultados sobre los datos del ECEMCA review of the literature shows that a large variety of terms is used to refer to the Möebius anomaly. These include diagnoses such as "Möebius syndrome", "Möebius sequence", "Möebius spectrum", "Möebius syndrome-limb abnormalities" "Möebius sequence-hypogeni- talism-cerebral, and skeletal malformations" and even three types of syndromes numbered "Möebius syndrome 1, 2 and 3", with different chromosomal loci. The Möebius anomaly is believed to comprise paralyses of some cranial nerves and their consequences. Thus, based in the concepts delineated by an International Working Group regarding errors of morphogenesis [Spranger y cols., 1982. J Pediatr 100:160-165], it constitutes a sequence: the "Möebius sequence." As such, it may be observed in different types of malformed infants, whether isolated (with only the Möebius sequence), with multiple congenital anomalies (MCA) patterns, or with different types of syndromes. That is, in multiple clinical presentations with different causes. It is important to keep these concepts in mind, because the term "syndrome" means that all affected infants will have similar characteristics, generally the same cause, and the same recurrence risk. If we do not use the current dysmorphological concepts, the information given to the family may be confuse or, what is worse, erroneous.N

Biología del desarrollo y genética molecular de los síndromes malformativos: Luces y Sombras de un Sistema Altamente Complejo

EditorialN

Deleción 14q proximal, presentación de dos casos y revisión de la literatura

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCHere we present two unrelated cases that came to our service for families that are looking for information on the diagnostic on malformation syndromes and infants with congenital defects. Both cases show as common signs psychomotor delay, microcephaly, corpus callosum agenesis and inespecific facial phenotype. We perform a high resolution G-bands karyotypes, and both of them showed a "de novo" deletion in the proximal region of a chromosome 14, with different break points but with a common region deleted. The karyotype of the first case was 46,XY, del(14)(q12;q21.1), and the karyotype of the second case 46,XX del(14)(q11.2;q13.1). We discussed the possible candidates genes that could be related with the phenotype and review the different reported cases.N

Other aspects of the epidemiological surveillance performed by ECEMC: Time distribution and distribution by Autonomous Regions of births from the immigrant population in Spain

Aspectos EpidemiológicosIt is well known that immigration has increased along the time in Spain, especially in the most recent years. We have analyzed data from ECEMC in order to quantify this phenomenon in the sample of 35,441 controls (newborn infants without congenital defects) registered by ECEMC in the period 1980-2009, since the group of immigrants usually has a set of characteristics which increase their offspring’s risk for being born with congenital anomalies. ECEMC gathers information on the birth place and ethnic group of parents and grandparents of both controls and cases registered with congenital anomalies. Most of immigrant parents (62.82%) come from non-european countries. Globally, the Autonomous Regions with the higher percentages of immigrant parents were the Balearic Islands (18%), Community of Madrid (15.84%), Comunidad Valenciana (15.16%) and Catalonia (13.08%). In the year 2009, however, the higher percentages were registered in Catalonia, followed by Community of Madrid, Balearic Islands and Comunidad Valenciana. There has been a statistically significant increase of births from immigrants along the time, from 1.89% of total control births in 1980-1985, up to 23.92% in the year 2009. This increase has been more pronounced for the group of immigrants from non-european countries. Since 1996, the proportion of births from non-European countries is higher than the counterpart of infants being born to European immigrants in Spain. Data from the different Autonomous regions mostly reflect this general tendency. In the groups of immigrants, the most frequent ethnic group was that of whites (96.84% among immigrants coming from European countries, and 41.73% among those coming from non-european countries). There is almost total concordance of data from ECEMC with the official data registered by INE (Spanish National Institute for Statististics). Knowing the magnitude of the different groups of immigrants in Spain is very important in order to properly design the different plans for prevention of congenital anomalies, according to the special risks of each population groupN

Clinical analysis of newborn infants with congenital defects registered in ECEMC: Distribution by etiology and ethnic groups

Dismorfología y Genética ClínicaIn 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.N

Present situation in Spain regarding the etiologic diagnosis in foetuses from termination of pregnancy (ToP) due to congenital defects. Guidelines for a minimum protocol

Dismorfología y Genética ClínicaSince 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.N

Monososomy 1p36: A clinically recognizable syndrome

Dismorfología, Citogenética y Clínica: Resultados sobre los datos del ECEMCPure 1p36 deletion is considered a new delineated syndrome that probably is a contiguous gene syndrome, presenting a pattern of clinical manifestation that may be recognizable. This includes moderate to severe psychomotor retardation, hypotonia, microcephaly, postnatal growth retardation, seizures and craniofacial dysmorphism (deep set eyes, low nasal bridge, large anterior fontanelle, midface hypoplasia) which should lead to perform a chromosomal study particularly focussed on this type of deletion. Terminal region 1p is difficult to visualize and its alterations will only be detected in a High Resolution G-band karyotype, followed by Fluorescence in situ Hybridization techniques (FISH). Here we present a case which was diagnosed as having a 1p36.22 deletion with High Resolution G-band karyotype confirmed by telomeric FISH.N

Security Guidelines for the Development of Accessible Web Applications through the implementation of intelligent systems

Due to the significant increase in threats, attacks and vulnerabilities that affect the Web in recent years has resulted the development and implementation of tools and methods to ensure security measures in the privacy, confidentiality and data integrity of users and businesses. Under certain circumstances, despite the implementation of these tools do not always get the flow of information which is passed in a secure manner. Many of these security tools and methods cannot be accessed by people who have disabilities or assistive technologies which enable people to access the Web efficiently. Among these security tools that are not accessible are the virtual keyboard, the CAPTCHA and other technologies that help to some extent to ensure safety on the Internet and are used in certain measures to combat malicious code and attacks that have been increased in recent times on the Web. Through the implementation of intelligent systems can detect, recover and receive information on the characteristics and properties of the different tools and hardware devices or software with which the user is accessing a web application and through analysis and interpretation of these intelligent systems can infer and automatically adjust the characteristics necessary to have these tools to be accessible by anyone regardless of disability or navigation context. This paper defines a set of guidelines and specific features that should have the security tools and methods to ensure the Web accessibility through the implementation of intelligent systems

Candida albicans Hyphal Extracellular Vesicles Are Different from Yeast Ones, Carrying an Active Proteasome Complex and Showing a Different Role in Host Immune Response.

Candida albicans is the principal causative agent of lethal fungal infections, predominantly in immunocompromised hosts. Extracellular vesicles (EVs) have been described as crucial in the interaction of microorganisms with their host. Since the yeast-to-hypha transition is an important virulence trait with great impact in invasive candidiasis (IC), we have addressed the characterization of EVs secreted by hyphal cells (HEVs) from C. albicans, comparing them to yeast EVs (YEVs). YEVs comprised a larger population of bigger EVs with mainly cell wall proteins, while HEVs were smaller, in general, and had a much higher protein diversity. YEVs were able to rescue the sensitivity of a cell wall mutant against calcofluor white, presumably due to the larger amount of cell wall proteins they contained. On the other hand, HEVs also contained many cytoplasmic proteins related to protein metabolism and intracellular protein transport and the endosomal sorting complexes required for transport (ESCRT) pathway related to exosome biogenesis, pointing to an intracellular origin of HEVs. Interestingly, an active 20S proteasome complex was secreted exclusively in HEVs. Moreover, HEVs contained a greater number of virulence-related proteins. As for their immunogenic role, both types of EV presented immune reactivity with human sera from patients suffering invasive candidiasis; however, under our conditions, only HEVs showed a cytotoxic effect on human macrophages and could elicit the release of tumor necrosis factor alpha (TNF-α) by these macrophages. IMPORTANCE This first analysis of HEVs of C. albicans has shown clear differences between them and the YEVs of C. albicans, showing their relevance and possible use in the discovery of new diagnostic markers and treatment targets against C. albicans infections. The data obtained point to different mechanisms of biogenesis of YEVs and HEVs, as well as different involvements in cell biology and host interaction. YEVs played a more relevant role in cell wall maintenance, while HEVs were more closely related to virulence, as they had greater effects on human immune cells. Importantly, an active 20S proteosome complex was described as a fungal-EV cargo. A deeper study of its role and those of many other proteins exclusively detected in HEVs and involved in different relevant biological processes of this fungus could open up interesting new areas of research in the battle against C. albicans

Johnson-McMillin syndrome (JMS): description of the first patient in Spain.

Dismorfología y Genética ClínicaThe JMS (OMIM: 147770) is a rare autosomal dominant neuroectodermal disorder characterized by alopecia, ear malformations, conductive hearing loss, anosmia/hyposmia, and hypogonadotropic hypogonadism. Morover, some additional features have been described so far (congenital heart defect, cleft palate, mild facial asymmetry, tendency to caries, and mental retardation). Herein we report on a patient with this condition who exhibits many of the features previously described, including alopecia, malformed auricles, conductive hearing loss, facial asymmetry, and developmental delay. Interestingly, she also has features that have not been reported yet, such as preauricular pits and tags, broad depressions at the external lateral areas close to the eyes, and an abnormal left lower eyelid. This phenotype supports the involvement of the ectoderm and neuroectoderm of the first two branchial arches in the embryologic basis of this condition. Indeed, alopecia, dental anomalies, defects of the choanae, part of the palatal valves, hypothalamic axis and hypogonadotropic hypogonadism, of epidermic origin, are derived from the ectoderm. Other defects as craniofacial alterations, including inner ear, preauricular tags, ear pits, and even microtia, and facial palsy, are derived from the neural crest, as also are the cardiac malformations. As far as we have known, the patient described here, represents the first case published from SpainN