What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Síndromes muy poco frecuentes

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCSince the year 2002, this Section of the Boletín del ECEMC: Revista de Dismorfología y Epidemiología, is dedicated to dysmorphology, cytogenetics and clinical analysis of congenital anomalies, and includes a chapter on syndromes with very low frequency. The aim of this chapter is to summarize the most important characteristics, the etiology, and the mechanisms involved in the selected syndromes. The low frequency of these syndromes, together with their probable decreasing birth prevalence due to the impact of prenatal diagnosis, imply that pediatricians and other health professionals would have less opportunity to know their clinical characteristics. This circumstance together with the overlapping of the clinical features among some of the syndromes, make difficult to perform an early diagnosis, which is important for genetic counselling, and to provide the most suitable treatment to each pacient. The syndromes included are: Aarskog, Freeman-Sheldon, Cleidocranial dysplasia, Noonan, Cardio-Facio-Cutaneous and Costello. In addition, a short summary about the differential diagnosis among Noonan, Cardio-Facio-Cutaneous and Costello syndromes is also included.N

Very low frequency Syndromes

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCThe aim of this chapter is to summarize updated knowledge about the clinical characteristics, etiology, genetic and molecular aspects, as well as mechanisms involved in syndromes having very low frequency, in order to promote their better recognition. During the last five years, a total of 30 syndromes have been published in this chapter of the Boletín del ECEMC. This issue includes the following selected syndromes: Crouzon, Pfeiffer, Apert, Saethre-Chotzen, Carpenter and Muenke. All share craniosynostosis as the main clinical feature but also present with other birth defects, the most important being limb malformations, specially syndactyly and polydactyly. Over 100 syndromes with craniosynostosis have been described, usually involving multiple sutures, and several of them are associated with limb malformations. The clinical overlapping between those syndromes makes difficult to perform a neonatal diagnosis, based on their clinical findings. However, molecular genetic testing, specifically of the FRGR1-3 and TWIST1 genes, could help to establish the diagnosis of some of them. Early diagnosis is important for establishing the most suitable treatment for each patient, as well as to offer an accurate genetic counselling and the possibility of preimplantational and/or prenatal diagnosis.N

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Corneal Thickness Response after Anesthetic Eye Drops: Our Own Results and Meta-Analysis

We aimed to test if there are different patterns in the central corneal thickness (CCT) response after instilling oxybuprocaine anesthetic eye drops and also to determine whether there is a significant change in the CCT. CCT was measured in 60 eyes of 60 healthy subjects before and during the hour after oxybuprocaine 0.4% eye drops were instilled. In addition, a systematic review and meta-analysis were carried out in order to answer the following PICO (patient, intervention, comparison, and outcome) question: What effect do anesthetic eye drops have on CCT values? We found no significant changes in the mean CCT values during the hour’s observation (ANOVA, p=0.209), and the meta-analysis revealed no statistically significant changes in the CCT after anesthesia (Q-Value = 1.111; p value = 1.000; I2 = 0.000; Tau2 = 0.000; Stderr = 0.020). However, we found three CCT response patterns 5 minutes after anesthesia: Pattern 1, subjects with no significant changes in their CCT values (n=14, 46.7%); Pattern 2, subjects with significant CCT increases (n=11, 36.7%); and Pattern 3, subjects with significant CCT decreases (n=5, 16.7%). In sum, there are no significant changes in the CCT after anesthesia, but there are three different CCT response patterns 5 minutes after anesthesia

Cross-language transfer of semantic annotation via targeted crowdsourcing: task design and evaluation

[EN] Modern data-driven spoken language systems (SLS) require manual semantic annotation for training spoken language understanding parsers. Multilingual porting of SLS demands significant manual effort and language resources, as this manual annotation has to be replicated. Crowdsourcing is an accessible and cost-effective alternative to traditional methods of collecting and annotating data. The application of crowdsourcing to simple tasks has been well investigated. However, complex tasks, like cross-language semantic annotation transfer, may generate low judgment agreement and/or poor performance. The most serious issue in cross-language porting is the absence of reference annotations in the target language; thus, crowd quality control and the evaluation of the collected annotations is difficult. In this paper we investigate targeted crowdsourcing for semantic annotation transfer that delegates to crowds a complex task such as segmenting and labeling of concepts taken from a domain ontology; and evaluation using source language annotation. To test the applicability and effectiveness of the crowdsourced annotation transfer we have considered the case of close and distant language pairs: Italian-Spanish and Italian-Greek. The corpora annotated via crowdsourcing are evaluated against source and target language expert annotations. We demonstrate that the two evaluation references (source and target) highly correlate with each other; thus, drastically reduce the need for the target language reference annotations.This research is partially funded by the EU FP7 PortDial Project No. 296170, FP7 SpeDial Project No. 611396, and Spanish contract TIN2014-54288-C4-3-R. The work presented in this paper was carried out while the author was affiliated with Universitat Politecnica de Valencia.Stepanov, EA.; Chowdhury, SA.; Bayer, AO.; Ghosh, A.; Klasinas, I.; Calvo Lance, M.; Sanchís Arnal, E.... (2018). Cross-language transfer of semantic annotation via targeted crowdsourcing: task design and evaluation. Language Resources and Evaluation. 52(1):341-364. https://doi.org/10.1007/s10579-017-9396-534136452