ABSTRACT
INTRODUCCIÓN: El Síndrome de CHARGE (SCH), es un síndrome genético de amplia variabilidad fenotípica, de he rencia autosómica dominante, causado por variantes patogénicas en el gen CHD7. OBJETIVO: Descri bir el amplio espectro fenotípico de un SCH neonatal, heterocigoto para el gen CDH7 y la utilidad de la secuenciación en la confirmación diagnóstica, considerando los diagnósticos diferenciales. CASO CLÍNICO: recién nacida prematura de 34 semanas, con antecedentes prenatales de polihidroamnios severo, translucencia nucal aumentada y foco hiperecogénico cardiaco, con estudio de TORCH antenatal, que descartó infección congénita. Al nacer se pesquisó parálisis facial periférica, atresia de coanas, dismorfias múltiples, cardiopatía congénita y coloboma retinocoroideo bilateral. Las neuroimágenes mostraron hipoplasia de cóclea y de canales semicirculares bilaterales e hipoplasia pontocerebelosa. Los potenciales evocados auditivos mostraron hipoacusia sensorioneural profunda derecha y anacusia izquierda. Evolucionó con hipocalcemia y alteraciones en la inmunidad, confirmándose un hipoparatiroidismo e hipoplasia de timo. El cariograma fue normal y la amplificación de sondas dependiente de ligandos múltiples (MLPA) excluyó microdeleción 22q11.2. La sospecha clínica de SCH se confirmó con la detección de una variante patogénica en el gen CHD7. CONCLUSIONES: La su perposición de características clínicas del SCH con otros síndromes genéticos requiere confirmación genética molecular considerando diferencias en evolución, terapias y riesgos de recurrencia.
INTRODUCTION: CHARGE syndrome is a genetic disorder of wide phenotypic variability, of autosomal dominant in heritance, caused by pathogenic variants in the CHD7 gene. OBJECTIVE: To describe the broad pheno typic spectrum of neonatal CHARGE syndrome, heterozygous for the CHD7 gene, and the usefulness of genome sequencing in diagnostic confirmation, considering differential diagnoses. CLINICAL CASE: 34-week preterm newborn, with severe prenatal history of polyhydramnios, increased nuchal trans- lucency, and hyperechogenic cardiac focus, with a TORCH study that ruled out congenital infection. Peripheral facial paralysis, choanal atresia, multiple dysmorphisms, congenital heart disease, and bilateral retinochoroidal coloboma were observed at birth. The neuroimaging study showed hypo plasia of the cochlea and bilateral semicircular canals, and pontocerebellar hypoplasia. The auditory evoked potentials showed deep right-sided sensorineural hearing loss and left anacusis. The patient developed hypocalcemia and immunological alterations, confirming hypoparathyroidism and thy mus hypoplasia. The karyogram was normal and 22q11.2 microdeletion was excluded through mul tiplex ligation-dependent probe amplification (MPLA). A pathogenic variant in the CHD7 gene was detected that confirmed the clinical suspicion of CHARGE syndrome. CONCLUSIONS: The overlap of clinical characteristics of CHARGE syndrome requires molecular genetic confirmation, considering differences in evolution, therapies, and recurrence risks with other genetic syndromes.
Subject(s)
Humans , Female , Infant, Newborn , DNA Helicases/genetics , DNA-Binding Proteins/genetics , CHARGE Syndrome/physiopathology , Phenotype , CHARGE Syndrome/diagnosis , CHARGE Syndrome/genetics , MutationABSTRACT
Los defectos del desarrollo se pueden deber a malformaciones congénitas, deformaciones o disrupciones. El 10% de las malformaciones se atribuyen a causas ambientales el 25% a factores genéticos y el 65% a factores desconocidos probablemente de orden multifactorial. Existe un período de mayor susceptibilidad frente a los teratógenos que corresponde a la etapa donde se están formando la mayoría de los órganos y sistemas. La ingestión de plantas teratogénicas puede dar lugar a anomalías congénitas en los fetos de animales. Los pesticidas como DDT, la contaminación de las aguas por mercurio y los disruptores endocrinos afectan la embriogénesis de las distintas especies del reino animal. También se consideran como factores causantes de malformaciones a los agentes ambientales infecciosos y a algunos medicamentos. Los agentes físicos como los aumentos de temperatura, las condiciones de hipoxia y las radiaciones afectan a distintos organismos, desde los peces al ser humano. La genética de las malformaciones ha sido difícil de establecer, principalmente porque la mayor parte de ellas se caracteriza por presentar manifestaciones fenotípicas diversas, que en muchos casos aparentemente no están relacionadas y que son variables para los individuos afectados. Por otra parte, los estudios realizados indican que frecuentemente, en la determinación genética de las malformaciones participan varios genes y las interacciones de éstos con el ambiente, aunque determinaciones monogénicas se han podido establecer para unos pocos casos. Ilustramos aquí estos dos tipos contrastantes de determinación genética, a través de la descripción de los factores genéticos que estarían involucrados en los defectos del tubo neural y en el síndrome de CHARGE, respectivamente.
Developmental defects may be due to congenital malformations, deformations or disruptions; 10% of malformations are caused by environmental factors, 25% by genetics factors and 65% are due to unknown multifactorial problems. There is a developmental period of greater susceptibility to teratogens, which corresponds to the stages when most organs and systems are being formed. Ingestions of teratogenics plants may result in congenital anomalies in animal foetuses. Pesticide such as DDT, water contamination with the Hg and the endocrine disrupters affect embryogenesis of different animal species. As factors that provoke malformations there are environmental agents, infections and some drugs. Physical agents such as increased temperature, hypoxic conditions and radiation, affect different organisms from fishes to human. Genetic of malformations have been difficult to establish, mainly because most of them are characterized by diverse phenotypic aspects, apparently not related and variable for the different affected organisms. On the other hand, studies realized indicate that frequently in the genetic determination of malformations several genes and their interactions with the environment are involved, although it has been possible to establish monogenic determination for a few cases. Here we contrast these two types of genetic determination, describing the genetic factors involved in the neural tube defects and the CHARGE syndrome, respectively.
Subject(s)
Congenital Abnormalities/genetics , Environment , CHARGE Syndrome/genetics , Neural Tube Defects/geneticsABSTRACT
Objetivo: Describir la epidemiologia local y la experiencia en el manejo de casos de atresia de coanas con la técnica de cirugía endoscópica transnasal e instrumental de poder. Diseño: Estudio retrospectivo. Metodología: Se toman 16 casos con diagnóstico de atresia de coanas, en los que fueron consideradas variables clínicas, método diagnóstico, lateralidad, tipo de atresia, manejo inicial y técnica quirúrgica. Se realizó análisis estadístico en Stata, versión 11.1. Resultados: En esta serie de casos, diez eran mujeres y seis hombres, con una relación mujer-hombre de 1,7:1; 56% de ellos fueron bilaterales, 56% de presentaron anomalías congénitas y la edad al diagnóstico fue postneonatal en el 81%. No se encontró asociación estadística entre sexo, tipo de atresia y lateralidad. El principal método diagnóstico fue la tomografía axial computarizada, en el 87,6% de los estudios. El 94% de los pacientes presentaron buen resultado quirúrgico funcional con la técnica endoscópica
Objective: Describe the local epidemiology and the experience in the management of choanal atresia with endoscopic transnasal approach and power instruments. Methodology: Retrospective study of 16 cases with diagnosis of choanal atresia was considered variable clinics, diagnosis method, laterality, type of atresia, initial management and surgical technique. We performed statistical analysis in Stata, version 11.1. Results: In this series of cases, 10 was women and 6 was men, relation 1,7:1; 56% had associated congenital anomalies, the age of diagnosis was post neonatal 81%. There was no statistical association between sex, type of atresia and latelality. The main method diagnosis was the TAC in 87.6%. 94% of the patients showed a good surgical outcome with functional endoscopic technique. Conclusions: The experience observed in this series of cases with the use of technique endoscopic transnasal and power instrumentation (Shaver - Drill), represent a form of technique minimal invasive approach for this type of nasal congenital pathology with low degree of morbility, complications and excellent functional results
Subject(s)
Humans , Choanal Atresia , Nasopharynx , CHARGE SyndromeABSTRACT
A síndrome de CHARGE é um conjunto especifico de malformações congênitas que podem comprometer o crescimento e o desenvolvimento da criança. O objetivo deste trabalho e relatar o caso de uma criança portadora desta síndrome e comparar suas características com aquelas apontadas na literatura. Para a execução do estudo foi solicitada a autorização do responsável pela criança e foram coletados os dados referentes ao exame físico e neurológico, incluindo resultados dos exames laboratoriais e radiológicos. Ao comparar o quadro da criança com os dados da literatura verificou-se a presença de quatro características mais freqüentes e quatro características menos freqüentes, as quais fornecem critérios para o diagnostico clinico da síndrome.
CHARGE syndrome it is a specific group of congenital malformations that can commit the child's growth and development. The objective of this paper was the presentation of a child with this syndrome and to compare its characteristics with those pointed in the literature. For the execution of the study it was requested the authorization of the responsible by the child and the referring data from physical and neurological exam were collected, including the results of laboratorial and radiological tests. When comparing the child's features with the data of the literature it was verified the presence of four more frequent characteristics and four less frequent characteristics, which supply the criteria for the clinical diagnosis of the syndrome.