A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones / About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations

El síndrome de Fraser o síndrome criptoftalmos/sindactilia es una enfermedad genética rara, cuyo diagnóstico se basa en una serie de criterios clínicos mayores y menores, y que puede apoyarse en pruebas genéticas. En este artículo se presenta el caso de una autopsia fetal de 37 semanas de gestación con sospecha de síndrome de CHAOS (síndrome obstructivo congénito de las vías aéreas altas). (AU)

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways). (AU)

Electronic health records contain dispersed risk factor information that could be used to prevent breast and ovarian cancer.

OBJECTIVE: The genetic testing for hereditary breast cancer that is most helpful in high-risk women is underused. Our objective was to quantify the risk factors for heritable breast and ovarian cancer contained in the electronic health record (EHR), to determine how many women meet national guidelines for referral to a cancer genetics professional but have no record of a referral. METHODS AND MATERIALS: We reviewed EHR records of a random sample of women to determine the presence and location of risk-factor information meeting National Comprehensive Cancer Network (NCCN) guidelines for a further genetic risk evaluation for breast and/or ovarian cancer, and determine whether the women were referred for such an evaluation. RESULTS: A thorough review of the EHR records of 299 women revealed that 24 (8%) met the NCCN criteria for referral for a further genetic risk evaluation; of these, 12 (50%) had no referral to a medical genetics clinic. CONCLUSIONS: Half of the women whose EHR records contain risk-factor information meeting the criteria for further genetic risk evaluation for heritable forms of breast and ovarian cancer were not referred.

Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System.

Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems. Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. Exposures: Ultra-rapid exome sequencing. Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%). Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

Taquicardia ventricular polimórfica catecolaminérgica com necessidade de implante de cardiodesfibrilador implantável (CDI): Um relato de caso / Ventricular Catecolaminergic Polymorphic Tachycardia (VCPT) with ICD implantation requirement: A case report

Relato de caso de uma paciente do sexo feminino, com 16 anos de idade à ocasião de sua admissão no Instituto de Cardiologia. A mesma foi encaminhada por serviço de saúde externo devido a síncopes durante atividade física e foi submetida à investigação, com diagnóstico final de taquicardia ventricular catecolaminérgica. Após a definição diagnóstica, foi realizado tratamento medicamentoso com betabloqueador, sendo necessário o implante de marcapasso definitivo por conta da incompetência cronotrópica secundária ao tratamento farmacológico instituído. Posteriormente, por persistência das arritmias ventriculares mesmo com o uso de terapia otimizada, optou-se por realizar um implante de CDI

Case report of a 16-year-old female patient at the time of her admission to the Institute of Cardiology. She was referred by an external healthcare service due to syncope during physical activity and was submitted to the investigation with a final diagnosis of catecholaminergic ventricular tachycardia. Once the diagnosis was established, the patient was administered a beta-blocker and definitive pacemaker implant was required due to chronotropic incompetence secondary to drug therapy. Subsequently, due to the persistence of ventricular arrhythmias despite the use of optimized therapy, we decided to implant an ICD

Thirteen years' experience of 893 PGD cycles for monogenic disorders in a publicly funded, nationally regulated regional hospital service.

This study provides an overview of preimplantation genetic diagnosis (PGD) for single gene diseases and the management of expanding indications in the context of a fully financially covered service at Montpellier's regional hospital centre. Within the framework of a restrictive law ruling PGD in France, only the parental genetic risk can be studied in embryos (concurrent aneuploidy screening is not allowed). PCR-based techniques were developed combining mutation detection and closely linked short tandem repeat markers within or flanking the affected genes, and set up more than 100 different robust fluorescent multiplex assays for 61 monogenic disorders. This strategy was used to analyse blastomeres from cleavage-stage embryos. Overall, 893 cycles were initiated in 384 couples; 727 cycles proceeded to oocyte retrieval and 608 cycles to embryo transfer, resulting in 184 deliveries. Clinical pregnancy rate per transfer, implantation and miscarriage rates were 33.6%, 25.1% and 8.8%, respectively. Our PGD programme resulted in the birth of 214 healthy babies for 162 out of 358 couples (45.3%), constituting a relevant achievement within an organizational framework that does not allow aneuploidy screening but provides equal access to PGD, both geographically and socioeconomically. This is a rare example of a fully free-of-charge PGD service.

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

Familial myelodysplastic syndrome/acute myeloid leukemia.

A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults are rapidly being identified. In recognition of the clinical impact of this emerging field, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have all added consideration of inherited predisposition to MDS/AML classification and management. Study of these disorders is providing unique insight into the biology of both sporadic and familial MDS/AML. International collaborative efforts to store germline tissue, document family histories, and pool data are essential to progress in diagnosing and treating both hereditary and sporadic forms of MDS/AML.

Actualisation sur l'hypoparathyroïdie : un peu de théorie, beaucoup de pratique: Update on hypoparathyroidism: a little theory, a lot of practice.

Parathormone (PTH), produced by parathyroid glands, is the main regulator of calcium homeostasis. Hypoparathyroidism (hypoPT), due to decrease of PTH production, is a rare disease. Symptoms are multiple, altering function of several organs and leading to a decrease of quality of life. Acquired etiologies, including thyroïdectomy, the main cause of hypoPT, can be distinguished from congenital etiologies, including genetic defects. HypoPT, which is classically treated by supplementation by calcium and active vitamin D, can now be treated by recombinant injection in certain indications as a poor control under classical therapy. Here are summarized current knowledge on etiologies, epidemiology, clinical manifestations and management of hypoPT.

Preimplantation genetic diagnosis after 20 years.

Preimplantation genetic diagnosis (PGD) should not be an option only for the few couples at risk of serious genetic conditions who can afford it. We appear to have lost sight of the original driving force behind the development of PGD, which is that most couples who carry a serious genetic disorder find it more acceptable to choose to conceive with healthy embryos tested in-vitro at preimplantation stages of development within the first week following fertilization, even if that means discarding those diagnosed as affected. It has been shown using cystic fibrosis as an example, that the cost savings to the US healthcare system of providing free IVF-PGD to all carrier couples compared to the lifetime costs of medical treatment for patients affected by this disease, run to dozens of billions of dollars. With the increasing emphasis in medicine on early diagnosis and prevention of disease together with the availability of new molecular genetic diagnostic tools, a national IVF-PGD programme seems to be the next step in modern health care.

Sanjad-Sakati syndrome in a neonate.

Congenital hypoparathyroidism, growth retardation and dysmorphism is a rare autosomal recessive syndrome among Arab population commonly known as Sanjad-Sakati syndrome(SSS).Several metabolic and septic complications are known to manifest in the neonatal age. We describe the first report of morbid pathological fractures affecting a neonate with SSS.

[Prenatal diagnostics and information to parents]. / Diagnósticos prenatales: información a los padres.

New screening and prenatal diagnostic techniques, require the Medicine professionals have a clear purpose for its realization, since the intention determined the act is determined in accordance with the values of the Medicine or becoming an event eugenics act by means of "therapeutic abortion". The Family Physician information about these techniques to pregnant women must be based on the status of science, facilitating the risk of loss fetal and false data positive informing of therapeutic possibilities and facilitating respect for the pregnant woman's decision of non-fulfillment of the screening. The information update according to the state of science, should be provided in writing and the informed consent of the patient should be obtained by all professionals involved in testing, with respect shows for the autonomy of the patient.

Monogenic diabetes in children and young adults: Challenges for researcher, clinician and patient.

Monogenic diabetes results from one or more mutations in a single gene which might hence be rare but has great impact leading to diabetes at a very young age. It has resulted in great challenges for researchers elucidating the aetiology of diabetes and related features in other organ systems, for clinicians specifying a diagnosis that leads to improved genetic counselling, predicting of clinical course and changes in treatment, and for patients to altered treatment that has lead to coming off insulin and injections with no alternative (Glucokinase mutations), insulin injections being replaced by tablets (e.g. low dose in HNFalpha or high dose in potassium channel defects -Kir6.2 and SUR1) or with tablets in addition to insulin (e.g. metformin in insulin resistant syndromes). Genetic testing requires guidance to test for what gene especially given limited resources. Monogenic diabetes should be considered in any diabetic patient who has features inconsistent with their current diagnosis (unspecified neonatal diabetes, type 1 or type 2 diabetes) and clinical features of a specific subtype of monogenic diabetes (neonatal diabetes, familial diabetes, mild hyperglycaemia, syndromes). Guidance is given by clinical and physiological features in patient and family and the likelihood of the proposed mutation altering clinical care. In this article, I aimed to provide insight in the genes and mutations involved in insulin synthesis, secretion, and resistance, and to provide guidance for genetic testing by showing the clinical and physiological features and tests for each specified diagnosis as well as the opportunities for treatment.

¿Colitis isquémica de base genética? / Genetic ischemic colitis?

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Transfusión en la cirugía intracraneal / Transfusion in intracraneal surgery

Fundamentos: Analizar la transfusión en los pacientes de cirugía intracraneal a partir de los datos del Conjunto Mínimo Básico de Datos del paciente. Métodos: Informes de alta de los pacientes intervenidos durante 1996, codificados según la Clasificación Internacional de Enfermedades (CIE-9-MC), evaluando: edad, sexo, los códigos de diagnósticos, de procedimientos, incluidas las transfusiones, y los códigos de las intervenciones quirúrgicas. Resultados: Fueron operados 203 pacientes, de los que se transfundieron 19 (9.4 por ciento). El mayor riesgo de transfusión ocurre en los pacientes con fractura de cráneo (18.5 por ciento), hemorragias intracraneales (12.1 por ciento) y tumoraciones benignas (10.3 por ciento). Mediante análisis univariante, se detecta una asociación estadísticamente significativa de la transfusión con el diagnóstico (p: 0.049), número de diagnósticos codificados (p: 0.049) y de técnicas quirúrgicas codificadas (p: 0.018), posibles indicadores indirectos de la severidad clínica y quirúrgica. Sin embargo mediante el análisis multivariante de regresión logística no se detectó ninguna asociación ajustada de las variables estudiadas con el riesgo de transfusión. Conclusiones: 1º Aunque no hemos podido encontrar un modelo predictor del riesgo de transfusión, este es mayor en los pacientes con fractura de cráneo, hemorragias intracraneales y tumores benignos. 2º Es coste-efectivo el poder monitorizar las transfusiones a partir de los datos administrativos del hospital, dada su fácil disponibilidad y los beneficios del análisis de los mismos. 3º Son necesarios ulteriores estudios para intentar definir con exactitud el subgrupo de los pacientes con mayor riesgo a priori de ser transfundido en la cirugía intracraneal (AU)