Relevancia del estudio genético de la amiloidosis cardíaca por transtiretina en el anciano / Importance of genetic study in elderly patients with transthyretin cardiac amyloidosis

Antecedentes y objetivo La amiloidosis cardiaca por transtiretina (AC-ATTR) es una enfermedad prevalente con la edad. Se recomienda realizar sistemáticamente un estudio genético incluso en los pacientes más añosos. Nuestro objetivo ha sido realizar un análisis de la prevalencia de amiloidosis por transtiretina hereditaria (ATTRv) en ancianos (≥75años) con AC-ATTR y sus implicaciones. Pacientes y método Estudio observacional retrospectivo de la cohorte de pacientes ancianos con AC-ATTR diagnosticados de acuerdo con el protocolo internacional. Analizamos los resultados de la secuenciación del gen TTR, las características diferenciales y sus implicaciones clínicas. Resultados Entre 2016 y 2022 se diagnosticaron 130 pacientes ancianos (89% cohorte) con AC-ATTR (85% varones). En 8 pacientes de los 123 con estudio genético se identificó una variante patogénica en TTR (6,5%), iniciándose tratamiento específico en 4 sujetos (50%). El estudio familiar identificó otro caso y 6 portadores asintomáticos. No hubo diferencias significativas entre características basales ni en los eventos clínicos. Conclusiones La prevalencia de ATTRv en ancianos con AC-ATTR fue del 6,5%, sin observarse características diferenciales que permitan guiar una indicación selectiva del análisis genético (AU)

Background and objective Cardiac transthyretin amyloidosis (CA-ATTR) is a prevalent disease with age. Genetic study is recommended, even in eldest patients. We aim to analyze the prevalence of hereditary transthyretin amyloidosis (ATTRv) in elderly patients (≥75years) with CA-ATTR and its implications. Patients and methodology Retrospective observational study of the cohort of elderly patients with CA-ATTR diagnosed according to the international recommended protocol. We analyze the results of sequencing TTR gene, the differential characteristics and their clinical implications. Results Between 2016 and 2022, 130 elderly patients (89% cohort) were diagnosed with CA-ATTR (85% male). In 8 of the 123 patients with a genetic study, a pathogenic variant in TTR was identified (6.5%), initiating specific treatment in 4 subjects (50%). The family study identified another case and 6 asymptomatic carriers. There were no significant differences between baseline characteristics or in clinical events. Conclusions The prevalence of ATTRv in elderly patients with CA-ATTR was 6.5% without observing differential characteristics that allow guiding a selective indication of genetic analysis (AU)

Importance of genetic study in elderly patients with transthyretin cardiac amyloidosis. / Relevancia del estudio genético de la amiloidosis cardíaca por transtiretina en el anciano.

BACKGROUND AND OBJECTIVE: Cardiac transthyretin amyloidosis (CA-ATTR) is a prevalent disease with age. Genetic study is recommended, even in eldest patients. We aim to analyze the prevalence of hereditary transthyretin amyloidosis (ATTRv) in elderly patients (≥75years) with CA-ATTR and its implications. PATIENTS AND METHODOLOGY: Retrospective observational study of the cohort of elderly patients with CA-ATTR diagnosed according to the international recommended protocol. We analyze the results of sequencing TTR gene, the differential characteristics and their clinical implications. RESULTS: Between 2016 and 2022, 130 elderly patients (89% cohort) were diagnosed with CA-ATTR (85% male). In 8 of the 123 patients with a genetic study, a pathogenic variant in TTR was identified (6.5%), initiating specific treatment in 4 subjects (50%). The family study identified another case and 6 asymptomatic carriers. There were no significant differences between baseline characteristics or in clinical events. CONCLUSIONS: The prevalence of ATTRv in elderly patients with CA-ATTR was 6.5% without observing differential characteristics that allow guiding a selective indication of genetic analysis.

Miopatía miotubular ligada al cromosoma X: informe clínico y revisión del fenotipo leve / X-linked myotubular myopathy: a clinical report and a review of the mild phenotype

Introducción: La miopatía miotubular ligada al X es una miopatía centronuclear rara que afecta aproximadamente a 1 de cada 50.000 recién nacidos varones causada por variantes patógenas en el gen de la miotubularina 1 (MTM1). La gravedad clínica varía; sin embargo, la necesidad de soporte ventilatorio ocurre casi invariablemente. Caso clínico: Presentamos el caso de un niño de 4 años que presentaba hipotonía muscular leve a los 12 meses, trastorno del lenguaje expresivo, retraso global del desarrollo y trastorno del procesamiento sensorial. La secuenciación clínica del exoma identificó la variante hemicigótica c.722G>A p.(Arg241His) en el exón 9 del gen de la miotubularina 1 (NM_000252.2). La madre es portadora heterocigota de la misma variante. Se estableció el diagnóstico de una forma leve de miopatía miotubular ligada al cromosoma X de herencia materna. El niño presentó una mejoría significativa con terapias del habla, ocupacional y física, sin intercurrencias respiratorias ni dependencia de ventilador. Conclusión: La presentación de una forma leve de esta miopatía miotubular, al notificarse más raramente, añadió desafío al diagnóstico. La combinación de hipotonía leve, dificultades de alimentación y trastorno del lenguaje expresivo debe hacer sospechar una enfermedad neuromuscular. Se carece de puntuaciones motoras o de desarrollo verificadas específicas de esta miopatía para determinar el pronóstico y la necesidad de otras terapias. Aunque actualmente la gravedad de la miopatía miotubular se clasifica según la dependencia del ventilador, esto puede ser insuficiente e inaplicable a los casos más leves. Es evidente la necesidad de un sistema de clasificación para los casos leves y moderados que evalúe la debilidad muscular y la fatiga, las limitaciones de la vida diaria, el retraso del desarrollo motor, las puntuaciones fenotípicas tempranas o las infecciones respiratorias recurrentes.(AU)

Introduction: X-linked myotubular myopathy is a rare centronuclear myopathy that affects approximately 1 in 50,000 male newborns caused by pathogenic variants in the myotubularin 1 gene (MTM1). The clinical severity varies, however the need for ventilatory support occurs almost invariably. Case report: We report the case of a 4-year-old boy presenting mild muscle hypotonia at 12 months-old, expressive language disorder, global developmental delay, and a sensory processing disorder. Clinical exome sequencing identified the hemizygous variant c.722G>A p.(Arg241His) in exon 9 of the myotubularin 1 gene (NM_000252.2). The mother is a heterozygous carrier of the same variant. A diagnosis of a mild form of maternal inherited X-linked myotubular myopathy was established. The child presented significant improvement with speech, occupational, and physical therapies, with no respiratory intercurrences or ventilator dependency. Conclusion: The presentation of a mild form of this myotubular myopathy, being less commonly reported, added challenge to the diagnosis. The combination of mild hypotonia, feeding difficulties and expressive language disorder should raise suspicion of a neuromuscular disease. There is a lack of verified motor or developmental scores specific to this myopathy to further determine prognosis and need of other therapies. While currently the severity myotubular myopathy is classified according to ventilator dependency, this may be insufficient and unapplicable to milder cases. There is an evident need for a grading system for mild and moderate cases assessing muscle weakness and fatigue, daily life limitations, motor developmental delay, early phenotypical scores, or recurrent respiratory infections.(AU)

Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).

Impacto de la percepción de riesgo de padecer cáncer en Consejo Genético Oncológico / Impact of cancer risk perception on Oncology Genetic Counseling

El Consejo Genético Oncológico (CGO) es una herramienta útil para la detección de familias con alto riesgo cáncer de mama/ ovario hereditario, con la detección de mutaciones patogénicas en los genes BRCA1 y 2. Objetivo: valorar la percepción de riesgo de cáncer en mujeres con historia personal y/o familiar de cáncer de mama/ ovario hereditario, valorar la percepción de riesgo en función de la detección de la presencia/ ausencia de una mutación patogénica en el estudio genético, y de la medida preventiva elegida tras la realización del estudio genético (seguimiento periódico o cirugía reductora de riesgo). Método: se realizó una valoración de variables sociodemográficas, clínicas y percepción de riesgo de cáncer retrospectivamente en un grupo de mujeres portadoras de mutación sometidas a estudio genético desde 1998, y prospectivamente en un grupo de mujeres sometidas a estudio genético a partir de 2015. La muestra global estaba compuesta por 262 mujeres (173 mujeres recién estudiadas y 89 mujeres portadoras de mutación estudiadas previamente). Resultados: se encontraron diferencias significativas en las mujeres que decidieron optar por una cirugía reductora de riesgo, que presentaban una percepción de riesgo mayor que las que eligieron seguimiento y se observó una disminución significativa de esa percepción tras llevar a cabo la cirugía. Conclusiones: se resalta la necesidad de evaluar la percepción de riesgo de las participantes en CGO. (AU)

The cancer genetic counseling oncology helps for detecting families at high risk for hereditary breast/ovarian cancer, due to BRCA1/2 pathogenic mutations. Objective: To assess the perception of cancer risk in women with a personal and/or family history of hereditary breast/ovarian cancer, assess the perception of risk based on the detection of the presence/absence of a pathogenic mutation, and the preventive measure chosen after completion of the study genetic (periodic follow-up or risk-reducing surgery). Method: an assessment of sociodemographic and clinical variables and perception of cancer risk was carried out retrospectively in a group of women carriers of the mutation who underwent genetic testing since 1998, and prospectively in a group of women who underwent genetic testing since 2015. The global sample was made up of 262 women (173 newly studied women and 89 previously studied mutation carrier women). Result: Significant differences were found in women who decided to opt for risk-reducing surgery, who presented a higher risk perception than those who chose follow-up, and a significant decrease in this perception was observed after carrying out the surgery. Conclusions: It is necessary to evaluate the perception of risk of the participants in CGO. (AU)

Protocolo genético en Atención Primaria para enfermedades raras: el síndrome de Wolfram como prototipo / Genetic protocol in primary care for rare diseases: Wolfram syndrome as a prototype

Las enfermedades raras, pese a su baja frecuencia individual, afectan globalmente al 7% de la población, por lo que el profesional de Atención Primaria (AP) tendrá varios de estos pacientes bajo seguimiento. El 80% de estas enfermedades tienen base genética, lo que hace fundamental un asesoramiento genético adecuado. El seguimiento de pacientes con síndrome de Wolfram (SW) puede servir para diseñar un protocolo susceptible de ser utilizado en el diagnóstico y manejo de otras entidades y ser utilizado por profesionales sanitarios para dar soporte a los pacientes, contando con la participación de profesionales sanitarios e investigadores especializados en el SW, los propios pacientes y su entorno. Se desarrollan los pasos fundamentales de todo procedimiento clínico genético, en el que la AP es clave para dar soporte a estas familias y transmitir de forma comprensible la información sobre los aspectos genéticos.(AU)

Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.(AU)

[Genetic protocol in primary care for rare diseases: Wolfram syndrome as a prototype]. / Protocolo genético en Atención Primaria para enfermedades raras: el síndrome de Wolfram como prototipo.

Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.

Genetics in congenital heart disease. Are we ready for it?

Genetics has rightly acquired an important place in almost all medical disciplines in recent years and this is certainly the case in the field of congenital cardiology. Not only has this led to greater insight into the pathophysiology of congenital heart defects but it also has a beneficial impact on patient management. Integration of clinical genetics in multidisciplinary centers of expertise for CHD is therefore a clear recommendation. Adult and pediatric cardiologists play a crucial role in the process of genetic evaluation of patients and families and should have be familiar with red flags for referral for further clinical genetic elaboration, counseling, and eventual testing. Some basic knowledge is also important for the correct interpretation of genetic testing results. In this review article, we provide a practical overview of what genetic evaluation entails, which type of genetic tests are possible today, and how this can be used in practice for the individual patient.

Consejo genético y detección de vías moleculares en pacientes con cáncer hereditario / Genetic advice and molecular pathways detection in patients with hereditary cancer

INTRODUCCIÓN: El cáncer de mama es la primera causa de muerte de la mujer en la Argentina, con una incidencia estimada de más de 19.000 casos nuevos por año. Dentro de estos, el tipo de cáncer hereditario más común es el de mama/ovario hereditario, provocado por mutaciones en los genes BRCA 1(Breast cáncer) y BRCA 2. A su vez el cáncer colorrectal es la segunda causa de muerte en Argentina, con una incidencia estimada de más de 11.000 casos nuevos por año. OBJETIVO: de la presente investigación es evaluar la utilidad de la realización de los estudios genéticos en personas con cáncer hereditario en el contexto del consejo genético, con un asesoramiento antes y después de realizarse la prueba genética POBLACIÓN Y MÉTODOS: Se estudiaron 34 mujeres con diagnóstico de cáncer de mama/ovario y 31 pacientes de ambos sexos con diagnóstico de cáncer colorrectal (CCR). En las mujeres se analizaron los genes BRCA 1 y 2 por secuenciación de próxima generación (NSG) y grandes rearreglos de los genes BRCA 1 y 2 por amplificación de sonda dependiente de la ligadura multiplex (MLPA). En las personas de ambos sexos se determinó la Inestabilidad de Microsatelites(IMS), el análisis de mismatch repair (MMR) por MLPA y la mutación del gen BRAF (Protooncogen B-Raf) RESULTADOS: Los resultados mostraron que las pacientes con cáncer de mama / ovario con antecedentes familiares tienen un alto porcentaje de BRCA negativo. En cuanto a los cambios fenotípicos, el más predominante en este estudio, fue el subtipo triple negativo y la paciente con BRCA 2 positivo presentó este fenotipo. Con respecto al estudio del cáncer de colon detectamos cuatro pacientes con IMS-alta y mutación del V600E del gen BRAF. Cuando se les realizó el análisis de MLPA en los genes MSH6, MLH1, MSH2 y PMS2 a los efectos de establecer la diferencia entre CCR y síndrome de Lynch, los resultados fueron negativos, por lo tanto, estos pacientes fueron diagnosticados como CCR esporádico. CONCLUSIONES: Como lo demuestra este trabajo, para el consejo genético, el estudio de vías moleculares en pacientes con cáncer hereditario es un instrumento de ayuda para la valoración del riesgo génico. (AU)

INTRODUCTION: Breast cancer is the leading cause of death of women in Argentina, with a estimated incidence of more than 19,000 new cases per year. Among these, the most common type of inherited cancer is the breast /ovarian caused by mutations in the BRCA1 and BRCA 2 genes. At the same time, the cancer colorrectal is the second cause of death in Argentina, with an estimated incidence of more than 11,000 new cases per year. OBJECTIVE: of the present investigation is to evaluate the usefulness of the realization of the genetic studies in people with hereditary cancer in the context of genetic counseling, with a advice before and after the genetic test. POPULATIONS AND METHODS: We studied 34 women diagnosed with breast / ovarian cancer and 31 patients of both sexes with diagnosis of colorectal cancer (CRC). In women, the BRCA 1 and 2 genes by next generation sequencing (NSG) and large rearrangements of BRCA 1 and 2 genes by probe amplification dependent on multiplex ligation(MLPA). The instability of microsatellites (IMS) was determined in people of both sexes, the analysis of mismatchrepair (MMR) by MLPA and the mutation of the BRAF gene. RESULTS: There results showed that patients with breast / ovarian cancer with a history family members have a high percentage of negative BRCA. As for the changes phenotypic, the most predominant in this study, was the triple negative subtype and the patient with positive BRCA 2 presented this phenotype. With respect to the study of colon cancer detected four patients with IMS-high and mutation of the V600E of the BRAF gene. When the MLPA analysis was performed on the MSH6, MLH1, MSH2 genes and PMS2, in order to established difference between CRC and Lynch syndrome, the results were negative and therefore these patients were diagnosed as sporadic CRC. CONCLUSIONS: As this work demonstrates, for him genetic counseling, the study of pathways molecules in patients with hereditary cancer is a helpful instrument for risk assessment. (AU)

Communication of Information about Genetic Risks: Putting Families at the Center.

Genetic information is a family affair. With the expansion of genomic technologies, many new causal genes and variants have been established and the potential for molecular diagnoses increased, with implications not only for patients but also their relatives. The need for genetic counseling and intrafamilial circulation of information on genetic risks grew accordingly. Also, the amount and, particularly, the complexity of the information to convey multiplied. Sharing information about genetic risks with family members, however, has never been an easy matter and often becomes a source of personal and familial conflicts and distress. Ethical requisites generally prevent healthcare professionals from directly contacting their consultands' relatives (affected or still at risk), who often feel unsupported throughout that process. We discuss here the communication of genetic risks to family members. We first consider genomic testing as a basis for family-centered health care, as opposed to a predominant focus on the individual. We reviewed the literature on sharing genetic risk information with family members, and the associated ethical issues for professionals. Some clinical cases are presented and discussed, and key issues for meeting the needs of individuals and families are addressed. We argue that genetic information is inextricably linked to the family and that communicating about genetic risks is a process grounded within the broader milieu of family relationships and functioning. We conclude for the need for a more family-centered approach and interventions that can promote sensitive attitudes to the provision of genetic information to and within the family, as well as its inclusion in educational and training programmes for genetic healthcare professionals.

Asociación vacterl: reporte neonatal / Vacterl Association: neonatal report

VACTERL es el acrónimo que asocia varias malformaciones congénitas, incluye mínimo tres: malformaciones vertebrales, atresia anal, anomalías cardiovasculares, fístula traqueo esofágica, atresia esofágica, malformaciones renales y displasia de extremidades; es un síndrome de etiología incierta, el diagnóstico prenatal se realiza entre la semana 18 a 20. Este caso es de un neonato con pabellones auriculares de implantación baja, cuello corto, tórax estrecho, ano imperforado, genitales ambiguos, malformaciones vertebrales sacro coccígeas y acortamiento de miembro inferior izquierdo, que requirió cirugía, con un pronóstico reservado, que nos hace considerar la extensa pluralidad clínica de casos VACTERL reportados sin un patrón de presentación estricto; ésta es una patología de baja prevalencia pero con elevada morbi-mortalidad, que requiere consejo genético.

VACTERL is the acronym that associates several congenital malformations, including at least three: vertebral malformations, anal atresia, cardiovascular anomalies, esophageal tracheal fistula, esophageal atresia, renal malformations and limb dysplasia; syndrome of uncertain etiology, prenatal diagnosis is performed between week 18 to 20. This case is a neonate with low-set ear pavilions, short neck, narrow thorax, imperforate anus, ambiguous genitalia, sacrococcygeal vertebral malformations and shortening of left lower limb, which required surgery, with a reserved prognosis, which not so long ago that most of the clinical history of VACTERL cases reported without a strict presentation pattern; this is a pathology of low prevalence but with high morbi-mortality, which requires genetic counseling.

An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots and Freckling. Part II. Other Skin Manifestations Characteristic of NF1. NF1 and Cancer. / Neurofibromatosis tipo 1: más que manchas café con leche, efélides y neurofibromas. Parte II. Actualización sobre otras manifestaciones cutáneas características de la enfermedad. NF1 y cáncer.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still based primarily on clinical observations. The 7 diagnostic criteria of the National Institutes of Health, which were established in 1988, include 3 skin manifestations (café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas). The age at which these diagnostic lesions appear is variable: onset can be late in some patients while others never develop certain symptoms. Definitive diagnosis may therefore be delayed by years. Although the appearance of the characteristic café-au-lait spots and freckling in the early years of childhood are very suggestive of the disease, these signs are not pathognomonic and, in isolation, do not constitute sufficient evidence to establish a definitive diagnosis. Thus, other diagnoses should be considered in patients whose only symptoms are café-au-lait spots and freckling. By contrast, the presence of multiple cutaneous neurofibromas or at least 1 plexiform neurofibroma is a very specific indication of NF1. Identification of the different types of neurofibroma allows us to confirm the diagnosis and initiate appropriate management.

Fenotipos neurológicos en pacientes estudiados con citogenética en el Hospital de Puerto Montt / Neurological phenotypes in cytogenic study from Puerto Montt Hospital patients

El examen citogenético, es una herramienta importante para confirmar el diagnóstico, manejo y consejo genético. El objetivo es analizar las características del fenotipo neuroconductual, protocolizar y orientar en la eficaz solicitud del estudio citogenético. Se revisaron las fichas clínicas de los pacientes controlados del policlínico de Neuropediatría del Hospital de Puerto Montt, con cariograma anormal entre los años 2007 y 2012. De 248 pacientes, 12% se identificó una alteración; 58% aberraciones estructurales, 20% aneuploidías, y 20% alteraciones genético - moleculares. Los elementos clínicos que se encontraron fueron microcefalia 48%, retraso mental 67%, historia familiar 67%, hipotonía 70%, convulsiones 41%, alteraciones del SNC 37%.

Cytogenetic examination is an important tool for confirming diagnosis, case management and genetic counseling. The aim is to analyze the characteristics of neurobehavioral phenotypes, formalize and guide the effective application of cytogenetics. The medical records of patients with abnormal karyotype seen between 2007 and 2012 at the Hospital of Puerto Montt's neuropaediatric outpatient clinic were reviewed. Of 248 patients, in 12% an alteration was identified; 58% structural aberrations, 20% aneuploidy, and 20% genetic-molecular alterations. The clinical elements found were 48% microcephaly, 67% mental retardation, 67% family history, 70% hypotonia, 41% seizures, 37% CNS disorders.

Importancia de alteración cromosómica en parejas, como causa de aborto recurrente: revisión sistemática de la literatura / Chromosomal alterations in couples with recurrent miscarriage: systematic review of the literature

Objetivo: Determinar la frecuencia de alteraciones genéticas en uno o ambos progenitores de parejas con aborto recurrente. Método: Se buscaron artículos en inglés en las bases de datos MEDLINE y PUBMED entre los años 1990 y 2013 que reportaran estudio de cariograma en parejas con aborto recurrente y que no se hubieran sometido a técnicas de reproducción asistida. Resultados: La frecuencia de alteraciones cromosómicas fue variable en los distintos trabajos analizados con variaciones importantes en el número de pacientes incluidos. Aunque los trabajos analizados usaron diferentes números para definir el aborto recurrente, no hubo diferencias en la frecuencia de alteraciones genéticas al considerar 2 o más abortos versus 3 o más. La translocación recíproca fue la alteración más frecuentemente encontrada. Las alteraciones cromosómicas fueron más frecuentes en mujeres que en hombres. Conclusión: El análisis cromosómico es fundamental en el estudio de las parejas con aborto recurrente. En aquellas parejas portadoras de alguna alteración, es esencial que se realice un consejo genético adecuado y se debe sugerir la realización de diagnóstico prenatal en embarazos futuros.

Objective: To determine the frequency of genetic alterations in couples with recurrent miscarriage. Methods: We searched articles in English in MEDLINE and PUBMED databases between 1990 and 2013, which reported karyotype analysis in couples with recurrent miscarriage and that had not been subjected to assisted reproduction techniques. Results: The frequency of chromosomal alterations differ among different studies, furthermore we found a significant variation in the number of patients included. Although articles studied used different numbers to define recurrent miscarriage, there were no significant differences in the frequency of genetic alterations among couples with at least 2 or at least 3 miscarriages. The reciprocal translocation alteration was the most frequently found genetic alteration. Chromosomal alterations were more frequent in women. Conclusion: Chromosomal analysis is essential in the study of couples with recurrent miscarriage. In those couples carriers of some alteration, is essential to perform a genetic counseling and should be offered prenatal diagnosis in future pregnancies.

The cytogenetic examination as a tool for the diagnosis of chromosomal disorders / Examinación citogenética como herramienta para el diagnóstico de los desórdenes cromosómicos

Clinically significant chromosomal abnormalities occur in about 1 percent of children born alive. The objective of this work was to offer the patients and the families in the community for the service of the Integrated Clinic of Uniara Health (Araraquara and region), the examination of cariotype (cytogenetic study) for confirmation or exclusion of the diagnostic suspicion of chromosomal abnormalities as well as information (genetic counseling) for the prevention of occurrence and/or recurrence of these anomalies. In the period of one year and four months these were carried out in the Integrated Clinic of Uniara Health and directed for the Laboratory of Cytogenetic Human of the same institution in 66 cytogenetic studies. In 44 patients (66.6 percent) the results were normal. In 22 (33.3 percent) examinations, alterations were found, meaning that the respective clinical pictures are decurrent of chromosomic alterations. The first cause within alterations noted was Down syndrome with a total of 15 examinations or 68.1 percent, the second cause of chromosomal anomaly was the Turner syndrome where the most important factor is 45, X, where 2 karyotypes of this type or 9.1 percent were found, syndromes as (Eduards syndrome, Patau syndrome, 3p- syndrome, 4p- syndrome and 6p-syndrome) diagnosed in our laboratory appeared less frequently corresponding to 22.7 percent of the studied anomalies. The work carried out constitutes a necessary diagnosis of the main chromosomal abnormalities through a low cost technique; it can be carried out easily and is reliable, making the cytogenetic examination available to the community and contributing significantly to the quality of life of patients.

Las anormalidades cromosómicas, clínicamente significativas, se presentan en aproximadamente 1 por ciento de los niños nacidos vivos. Este trabajo tiene el objetivo de ofrecer a los pacientes y /o a sus familiares el servicio de la Clínica Integrada de la Salud de Uniara (Araraquara y Región), el examen de cariotipo (estudio citogenético) para la confirmación o la exclusión de sospecha de anomalías cromosomales diagnosticadas, así como otorgar información (consejo genético) para la prevención de las posibles anomalías y /o la repetición de éstas. En un año y cuatro meses fueron realizados 66 estudios de citogenética en la Clínica Integrada de Uniara, dirigida por el Laboratorio de Citogenética Humana de la misma institución. En 44 pacientes (66,6 por ciento) los resultados fueron normales. En 22 (33,3 por ciento) de los exámenes, se encontraron alteraciones, compatibles con alteraciones cromosómicas. La primera causa de anomalías cromosómica fue el síndrome de Down, totalizando 15 exámenes (68,1 por ciento), la segunda causa fue el síndrome de Turner, con dos cariotipos (9,1 por ciento) en la forma más importante 45, X. Por otra parte, se encontró que los síndromes de Eduards, de Patau, 3p-síndrome de Down, síndrome 4p-6p, diagnosticados en nuestro laboratorio, presentaban baja frecuencia de aparición, representando el 22,7 por ciento de las anomalías estudiadas. Este trabajo permitió realizar un diagnóstico preciso de las anomalías cromosomales, principalmente a través de una técnica de bajo costo, fácil ejecución y buena confiabilidad, técnicas que están disponibles para el examen citogenético para la comunidad y así contribuir de manera significativa en la calidad de vida de los pacientes.

Estrategias y estudios para desarrollar el asesoramiento genético: municipio Pinar del Río, 2000-2006 / Strategies and Studies for the Development of the Genetic Assessment: Pinar del Rio Municipality, 2000-2006

Aquellos padres que han tenido un hijo con algún defecto congénito deben reflexionar acerca de los factores que han podido originar tal condición, en especial si existe riesgo que los niños que tengan en un futuro pueden verse igualmente afectados. Se propone una estrategia para lograr la excelencia en los servicios de Asesoramiento Genético, partiendo del estudio de los indicadores del programa de genética del (2000_2006) y evaluando el comportamiento de su efectividad, involucrando además los aspectos éticos y bioéticos. Se realizó un estudio descriptivo, retrospectivo y de corte transversal en el Municipio Pinar del Río en los periodos comprendidos entre (2000-2003) y (2004-2006), se seleccionaron mediante muestreo no probabilístico, 50 familias de este municipio, atendidos en los Servicios de Genética por diversos motivos, se les aplicó mediante la entrevista una encuesta que evaluó variables relacionadas con la efectividad de Asesoramiento Genético, satisfacción con el servicio y otras. Como resultados del trabajo realizado se recoge una mejoría en los indicadores de cobertura del Programa de Genética, pero aún está por debajo del 100%, hay un alto por ciento en la clasificación de Buena en todos los aspectos que miden la efectividad, el 94% de los encuestados están satisfechos con el Asesoramiento Genético.Las estrategias propuestas están encaminadas a lograr la excelencia en el Asesoramiento Genético en el municipio Pinar del Río.

Those parents with a child with some congenital defect should be aware of the factors responsible of such condition, and if it is possible that future children could be affected similarly. A strategy for attaining the excellence in the genetic training is proposed according to the indicators of the 2000-2006 Genetic Program and it was also evaluated the effectivity of this program including the ethical and bioethical aspects. A descriptive retrospective and cross sectional study was carried out in Pinar del Rio municipality during 2000-2003 and 2004-2006. Fifty families from this municipality were chosen by means of a non-probabilistic sample and they were assisted in the Department of Genetics due to many reasons, they were surveyed evaluating those variables related to the effectivity of the Genetic Assessment, agreement with the service and so on. It is observed an improvement in the indicators of the Genetic Program, but it is yet fewer than 100% existing a high percentage in the classification of "Good", 94% of those surveyed parents agree with the Genetic Assessment. The proposed strategies are aimed at attaining the excellence condition in the Genetic assessment of Pinar del Rio municipality.

Registro genético preventivo automatizado de la enfermedad poliquística renal autosómica dominante

Se decidió crear un registro genético automatizado de la enfermedad poliquística renal autosómica dominante ya que es un fenómeno común y existe un programa nacional para su atención. Se empleó una metodología desarrollada por los autores para facilitar el estudio y seguimiento sistemático de muchas familias y su atención genética. Se logró en los primeros 3 años de funcionamiento, la caracterización clínica, genética y epidemiológica de 111 familias y se comprobó la factibilidad de la metodología desarrollada. Se les ofreció asesoramiento genético y seguimiento a 2 870 personas afectadas o con riesgo y se diseñaron varias investigaciones que contribuyeron a mejorar su atención y seguimiento.

It was decided to created an automated genetic registry of the autosomal dominant polycystio kidney disease, taking into account that it is a common phenomenon and that there is a national program for its attention. A methodology developed by the authors was used to enable the study and systematic follow-up of many families and their genetic attention. The clinical, genetic and epidemiological characterization of 111 families was attained during the first three years and the feasibility of the methodology was proved. 2 870 affected patients or at risk received genetic counseling and follow-up. Several investigations were designed to improve their attention and follow-up.

Malformaciones del sistema nervioso central en una familia

Se reporta la aparición de 3 malformaciones del sistema nervioso central (2 defectos del tubo neural y una hidrocefalia) en la progenie de un matrimonio entre primos y se establece una posible relación entre la aparición de estos defectos y las herencias multifactorial y autosómica recesiva. Se recomienda evitar el matrimonio entre parientes, así como ofrecer asesoramiento genético y diagnóstico prenatal a todas las personas que han procreado un hijo con malformaciones del sistema nervioso central.

It is reported the appearance of 3 malformations of the central nervous system (2 defects of the neural tube and 1 hydrocephaly) in the offspring of a marriage between cousins. A possible relationship between appearance of these defects and the multifactorial and recessive autosomal inheritances is established. It is recommended to avoid marriage between relatives, as well as to offer genetic counseling and prenatal diagnosis to all those persons who had procreated a child with malformations of the CNS.