Diagnóstico genético preimplantacional / Preimplantation genetic diagnosis

El diagnóstico genético preimplantacional (DGP) es un procedimiento que analiza el material genético de embriones formados por fertilización in vitro (FIV) para su selección y trasferencia al útero, con el fin de obtener un embarazo con feto genéticamente sano. El DGP se ha utilizado para el estudio de anomalías cromosómicas, enfermedades monogénicas, algunos tipos de cáncer y últimamente, para el genotipado del embrión como donante potencial de células madre hematopoyéticas para tratar a hermanos con enfermedades genéticas graves que precisan trasplante de dichas células. El DGP es un método complementario al diagnóstico prenatal tradicional que, al tratarse de un feto no afectado, evita la difícil decisión de interrumpir o no una gestación. Es este artículo revisaremos las principales técnicas de DGP, sus indicaciones, sus ventajas e inconvenientes y algunos aspectos éticos, sociales y legales del procedimiento (AU)

Preimplantation genetic diagnosis (PGD) is a method to analyse the genetic make-up of embryos formed by in vitro fertilization (IVF) for their selection to be transferred to the uterus and stablish a pregnancy with a genetically healthy fetus. PGD has been used to look for chromosomal abnormalities, monogenic diseases, some types of cancer, and lately, to genotype the embryo, who will be used as a potential donor of hematopoietic stem cells which can subsequently be used to treat sibs with severe genetic disease that need transplant of those cells. PGD is a complementary method to traditional prenatal diagnosis that avoids the difficult choice of termination of a pregnancy by starting pregnancies with unaffected embryos. In this review we include the main techniques used in PGD, its indications, advantages and disadvantages and some ethical, social and legal aspects of the procedure (AU)

[Clinical guide to the management of patients with Beckwith-Wiedemann syndrome]. / Guía clínica para el seguimiento de pacientes con síndrome de Beckwith-Wiedemann.

Beckwith-Wiedemann syndrome (BWS) is characterized by congenital overgrowth, macroglossia and omphalocele or umbilical hernia. Children with BWS may also have all or some of the following features: asymmetry (hemihypertrophy) of the limbs, torso or face, hypoglycemia, organomegaly, ear pits or creases, and embryonal tumors. The frequency of BWS is approximately 1:14,000 births. We present a guide for the management of children with BWS aimed at helping pediatricians and general practitioners or specialists in the clinical follow-up of these patients. This guide has been structured according to different age groups and is based on published evidence.

[Evaluation and diagnosis of patients with genetic mental retardation: standardised clinical evaluation protocols]. / Evaluación y diagnóstico del paciente con retraso mental de origen genético: protocolos estandarizados de evaluación clínica.

INTRODUCTION AND AIMS: Mental retardation (MR) affects approximately 2-3% of the general population and around 75% of the known causes of MR are thought to have a genetic origin. The aim of this work is to describe a standardised model of diagnostic approach to patients with mental retardation of a genetic origin (MRGO). DEVELOPMENT: The clinician has to draw up a detailed case history and carry out a thorough dysmorphological physical examination that enables a reasonable differential diagnosis to be reached. The next step will be to request the complementary studies needed to confirm or reject the initial suspected diagnosis. Accurate information about the personal, prenatal (pregnancy) and perinatal (childbirth) history must also be collected. The postnatal history will also provide relevant clinical information. The familial history is a fundamental element of any genetic disease and must be gathered by drawing up the family tree or lineage. The physical and dysmorphological examination must be ordered, completed and detailed, and measurements of the somatometric parameters required to demonstrate and quantify the existence of an anomaly in any anatomical structure will also have to be made. Photos of the patient are a great aid because they allow comparison with recognisable dysmorphic syndromes. The last phase involves requesting complementary studies, including consultations with other specialists. The confirmation or exclusion of MR usually results from biochemical-metabolic, cytogenetic or molecular studies. CONCLUSIONS: In cases of MRGO a good patient record accompanied by a thorough physical and dysmorphological study allow the clinical geneticist to orientate the diagnosis in the right direction and to request the specific genetic laboratory tests to confirm (or reject) its causation.

Evaluación y diagnóstico del paciente con retraso mental de origen genético: protocolos estandarizados de evaluación clínica / Evaluation and diagnosis of patients with genetic mental retardation: standardised clinical evaluation protocols

Introducción y objetivo. El retraso mental (RM) afectaaproximadamente al 2-3% de la población general. De las causasde RM conocidas, alrededor del 75% se consideran de base genética.El objetivo de este trabajo es exponer un modelo estandarizadode aproximación diagnóstica al paciente con retraso mental de origengenético (RMOG). Desarrollo. El especialista clínico deberárealizar una anamnesis detallada y una exploración física dismorfológicacompleta que le permitan obtener un diagnóstico diferencialrazonable. El siguiente paso será solicitar los estudios complementariosnecesarios para confirmar o descartar la sospecha diagnósticacorrespondiente. Deberá obtenerse información precisa sobrelos antecedentes personales, prenatales (embarazo), perinatales(parto). La historia posnatal también proporcionará informaciónclínica relevante. La historia familiar es un apartado fundamentalen cualquier enfermedad genética y debe recogerse en elcorrespondiente árbol familiar o pedigrí. La exploración física ydismorfológica debe también ordenarse, completarse y detallarse,y obtener las mediciones de parámetros somatométricos necesariaspara demostrar y cuantificar la existencia de una anomalía en cualquierestructura anatómica. La toma de fotografías del paciente esde gran ayuda para la comparación con síndromes dismórficos reconocibles.En la última fase se solicitarán los estudios complementarios,con inclusión de las interconsultas con otros especialistas.La confirmación o exclusión de RM suele proceder de estudiosbioquimicometabólicos, citogenéticos o moleculares. Conclusión.En los casos de RMOG, una buena historia clínica acompañada deuna exploración física y dismorfológica completa permiten al genetistaclínico orientar adecuadamente el diagnóstico y solicitarlos estudios genéticos de laboratorio específicos para confirmar (odescartar) su etiología

Introduction and aims. Mental retardation (MR) affects approximately 2-3% of the general population and around75% of the known causes of MR are thought to have a genetic origin. The aim of this work is to describe a standardised model ofdiagnostic approach to patients with mental retardation of a genetic origin (MRGO). Development. The clinician has to draw upa detailed case history and carry out a thorough dysmorphological physical examination that enables a reasonable differentialdiagnosis to be reached. The next step will be to request the complementary studies needed to confirm or reject the initialsuspected diagnosis. Accurate information about the personal, prenatal (pregnancy) and perinatal (childbirth) history must alsobe collected. The postnatal history will also provide relevant clinical information. The familial history is a fundamental elementof any genetic disease and must be gathered by drawing up the family tree or lineage. The physical and dysmorphologicalexamination must be ordered, completed and detailed, and measurements of the somatometric parameters required to demonstrateand quantify the existence of an anomaly in any anatomical structure will also have to be made. Photos of the patient are a greataid because they allow comparison with recognisable dysmorphic syndromes. The last phase involves requesting complementarystudies, including consultations with other specialists. The confirmation or exclusion of MR usually results from biochemicalmetabolic,cytogenetic or molecular studies. Conclusions. In cases of MRGO a good patient record accompanied by a thoroughphysical and dysmorphological study allow the clinical geneticist to orientate the diagnosis in the right direction and to requestthe specific genetic laboratory tests to confirm (or reject) its causation

Nuevos métodos de diagnóstico del síndrome X frágil:estudio de la FMRP en sangre y pelo / New methods for the diagnosis of fragile X syndrome: a study of the FMRP in blood and hair

Introducción. El síndrome X frágil (SXF) es la causa más frecuente de retraso mental hereditario. Aunque la mayoría de los pacientes afectados, especialmente los varones, presentan un fenotipo característico, es preciso el estudio molecular del gen FMR1 para confirmar el diagnóstico, en dependencia del número de expansiones del triplete CGG en dicho gen. Desarrollo. En los últimos años se ha desarrollado una técnica inmunohistoquímica que permite el estudio de la expresión de la proteína codificada por el gen FMR1, denominada FMRP (Fragile-X Mental Retardation Protein), inicialmente en linfocitos de sangre periférica y más recientemente en raíces de cabello, que permite identificar sin ambigüedades a varones afectados de SXF. Las ventajas de esta técnica con respecto al estudio molecular convencional es su rapidez (resultados en pocas horas), bajo coste y facilidad de obtención de las muestras, en el caso de los cabellos con un método incruento. Los varones afectados muestran niveles sensiblemente inferiores a los varones normales, sin solapamiento en los niveles de expresión respectivos. Estas afirmaciones son válidas tanto para el test en sangre como en raíces de cabello. En mujeres, la interpretación es más complicada debido a la inactivación al azar de uno de los cromosomas X, aunque los estudios iniciales han permitido diferenciar claramente el nivel de expresión de la FMRP en cabellos de mujeres con mutación completa y con cierto grado de retraso intelectual y el de mujeres normales con o sin premutación. Conclusión. Basándonos en los estudios realizados hasta la fecha, podemos concluir que el test FMRP es un eficaz y barato método de despistaje inicial del SXF (AU)

[New methods for the diagnosis of fragile X syndrome: a study of the FMRP in blood and hair]. / Nuevos métodos de diagnóstico del síndrome X frágil: estudio de la FMRP en sangre y pelo.

INTRODUCTION: Fragile X syndrome (FXS) is the commonest cause of hereditary mental retardation. Although most affected patients, especially males, have a typical phenotype, molecular studies of the FMR1 gene are necessary to confirm the diagnosis, depending on the number of repeats of the CGG triplet of the gene. DEVELOPMENT: In recent years an immunohistochemical technique has been developed which permits the study of the expression of the protein codified by the FMR1 gene, known as FMRP (Fragile X Mental Retardation Protein). This was done initially in peripheral blood lymphocytes and more recently in hair roots, thus permitting definite identification of males affected by FXS. The advantages of this technique compared with conventional molecular studies are speed (results available in a few hours), lower cost and ease of sample obtention, that in the case of hair roots is non-invasive. The affected males had significant lower levels of FMRP expression than normal or non fragile X males, without overlapping. This finding was observed in blood and hair roots. In females, interpretation is more difficult due to random inactivation of one of the X chromosomes. However, preliminary studies have shown that the level of FMRP expression in hair roots of females with the full mutation (usually with some degree of mental retardation) is significantly lower when compared to premutation carriers or normal females. CONCLUSION: The FMRP test, either in blood or hair, is an easy, cost-effective method for screening FXS in males with idiopathic mental retardation.

Phenotypic variability in the Baller-Gerold syndrome: report of a mildly affected patient and review of the literature.

We report a patient with a mild form of the Baller-Gerold syndrome (craniosynostosis-radial aplasia syndrome). The patient, a 3-year 3 month-old boy, has trigonocephaly with bilateral absent radii and thumbs. His growth parameters and psychomotor development have been normal. No visceral anomalies were found. This patient represents a new case of the rare mild form of the syndrome.

[Cortical evoked auditory evoked potentials in a series of patients who had bacterial meningitis during childhood]. / Potenciales evocados auditivos corticales (PEAC) en una serie de pacientes que han padecido meningitis bacteriana en la edad pediátrica.

Cortical auditory evoked potentials (CAEP) were recorded from scalp electrodes in 47 patients, who survived to bacterial meningitis in their childhood. CAEP were obtained from 1 month to 8 years after recovering from acute disease. Neisseria meningitidis was the microorganism more frequently isolated from CSF (43.5%). Exclusively abnormal values in amplitude of CAEP were registered in 15 cases (32%), mainly at the lower tones explored; 14 of them were subjected to conventional audiometric test, which demonstrated unilateral hearing loss only in 2. No alterations in the latency of P2 wave were seen. We recommend to include CAEP in search of hearing disorders in younger children after recovering from meningitis, since they can detect lesions in cortical-subcortical auditory tracts, which otherwise could go unnoticed.