Congenital hearing loss: a literature review of the genetic etiology in a Mexican population.

Hearing loss is the most frequent sensory disorder, with an incidence of 1:1500 live newborns. In more than 50% of patients, it is associated with a genetic cause, while in up to 30% of cases, it is related to syndromic entities. We performed a literature review of studies on congenital hearing loss of genetic origin in the Mexican population. We identified eight reports that showed that the pathogenic variants most frequently associated with hearing loss are related to the GJB2 gene, although in a low percentage (3%). Other mutations were identified in the GJB6, SLC26A4, or CHD23 genes. On this basis, a possible diagnostic strategy in Mexican patients with hearing loss is to consider an initial screening of these three genes. If these genes were negative for pathogenic variants, the following steps would be to consider second-generation sequencing analysis focused on panels of genes associated with hearing loss, isolated or syndromic, and if necessary, to perform exome or whole-genome analysis. Establishing an etiologic cause is critical in clinically evaluating patients with congenital hearing loss and their families. It can help determine rehabilitation strategies, such as hearing aids or cochlear implants and provide information on disease progression and genetic counseling in this population.

La pérdida auditiva es la alteración sensorial más frecuente, con una incidencia de 1:1500 recién nacidos vivos. En más del 50% de los pacientes se asocia con una causa genética, mientras que en más del 30% de los casos se asocia con entidades sindrómicas. Se llevó a cabo una revisión de la literatura de las investigaciones sobre la pérdida auditiva congénita de origen genético en la población mexicana. Se identificaron ocho reportes en los que se demostró que las variantes patogénicas más frecuentemente asociadas con pérdida auditiva se encuentran en el gen GJB2, aunque en un porcentaje bajo (3%). Se identificaron otras mutaciones en los genes GJB6, SLC26A4 o CHD23. Con base en esta información, una posible estrategia diagnóstica en pacientes mexicanos con pérdida auditiva es considerar un primer paso en el tamiz diagnóstico con los tres genes mencionados. Si estos genes fueran negativos para variantes patogénicas, el siguiente paso sería considerar el análisis por secuenciación de segunda generación enfocado en paneles de genes asociados con pérdida auditiva, tanto aislada como sindrómica, y en caso necesario, realizar el análisis del exoma o del genoma completo. Establecer una causa etiológica es un componente crítico en la evaluación clínica de los pacientes con pérdida auditiva congénita, ya que puede ayudar a determinar las estrategias de manejo y rehabilitación, como el uso de auxiliares auditivos o implantes cocleares, proporcionar información sobre la progresión de la enfermedad y dar asesoramiento genético en esta población.

Congenital hearing loss: a literature review of the genetic etiology in a Mexican population / Pérdida auditiva congénita: revisión de la etiología genética en la población mexicana

Abstract Hearing loss is the most frequent sensory disorder, with an incidence of 1:1500 live newborns. In more than 50% of patients, it is associated with a genetic cause, while in up to 30% of cases, it is related to syndromic entities. We performed a literature review of studies on congenital hearing loss of genetic origin in the Mexican population. We identified eight reports that showed that the pathogenic variants most frequently associated with hearing loss are related to the GJB2 gene, although in a low percentage (3%). Other mutations were identified in the GJB6, SLC26A4, or CHD23 genes. On this basis, a possible diagnostic strategy in Mexican patients with hearing loss is to consider an initial screening of these three genes. If these genes were negative for pathogenic variants, the following steps would be to consider second-generation sequencing analysis focused on panels of genes associated with hearing loss, isolated or syndromic, and if necessary, to perform exome or whole-genome analysis. Establishing an etiologic cause is critical in clinically evaluating patients with congenital hearing loss and their families. It can help determine rehabilitation strategies, such as hearing aids or cochlear implants and provide information on disease progression and genetic counseling in this population.

Resumen La pérdida auditiva es la alteración sensorial más frecuente, con una incidencia de 1:1500 recién nacidos vivos. En más del 50% de los pacientes se asocia con una causa genética, mientras que en más del 30% de los casos se asocia con entidades sindrómicas. Se llevó a cabo una revisión de la literatura de las investigaciones sobre la pérdida auditiva congénita de origen genético en la población mexicana. Se identificaron ocho reportes en los que se demostró que las variantes patogénicas más frecuentemente asociadas con pérdida auditiva se encuentran en el gen GJB2, aunque en un porcentaje bajo (3%). Se identificaron otras mutaciones en los genes GJB6, SLC26A4 o CHD23. Con base en esta información, una posible estrategia diagnóstica en pacientes mexicanos con pérdida auditiva es considerar un primer paso en el tamiz diagnóstico con los tres genes mencionados. Si estos genes fueran negativos para variantes patogénicas, el siguiente paso sería considerar el análisis por secuenciación de segunda generación enfocado en paneles de genes asociados con pérdida auditiva, tanto aislada como sindrómica, y en caso necesario, realizar el análisis del exoma o del genoma completo. Establecer una causa etiológica es un componente crítico en la evaluación clínica de los pacientes con pérdida auditiva congénita, ya que puede ayudar a determinar las estrategias de manejo y rehabilitación, como el uso de auxiliares auditivos o implantes cocleares, proporcionar información sobre la progresión de la enfermedad y dar asesoramiento genético en esta población.

Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.

Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc.

Síndrome de pendred: A propósito de un caso

Objetivo: Presentar caso clínico de Síndrome de Pendred, patología poco frecuente en la edad pediátrica que engloba sordera congénita y bocio. Caso clínico: Preescolar femenina de 5 años y 4 meses, cuya madre refiere enfermedad actual de 3 meses de evolución caracterizada por presentar aumento progresivo de volumen en cara anterior de cuello, sin cambios de coloración, ni temperatura, no doloroso, concomitantemente somnolencia, estreñimiento e hipoactividad. Examen Físico: Peso 14,700 Kg (

Objective: To present a clinical case of Pendred syndrome, a rare pathology in children that includes congenital deafness and goiter. Clinical case: Preschool female 5 years and 4 months of age, whose mother refers disease of 3 months of evolution characterized by progressive increase in volume of the anterior neck, without redness, heat, or pain; concomitantly drowsiness, constipation and hypoactivity. Physical Examination: Weight 14.700 Kg (

Importancia del diagnóstico de mutaciones en el gen de la conexina 26 en el manejo integral de la sordera congénita no sindrómica / Importance of the diagnosis of connexin 26 gene mutations in the integral management of non-syndromic congenital deafness

Introducción. La sordera congénita es un problema de salud pública. Su incidencia en México es de 2-3 por cada 1000 recién nacidos. El diagnóstico oportuno con el tamiz auditivo neonatal es fundamental para un mejor pronóstico funcional. Aproximadamente 70% de las sorderas congénitas son de origen genético, con herencia autosómica recesiva. La mayoría de estos casos se asocia con mutaciones en el gen GJB2 , que codifica para la proteína conexina 26. Hay tres mutaciones reportadas como las más frecuentes en este gen: c.35delG, c.167delT y c.235delC. Métodos. Previo consentimiento informado de los pacientes, se obtuvo 1 ml de sangre periférica para la extracción de ADN. Mediante las técnicas de PCR-RFLP o PCR seguida de secuenciación, se buscaron las tres mutaciones más frecuentes del gen GJB2 . Resultados. Se realizó el estudio molecular en 11 pacientes: Se encontró un cambio en la secuencia codificante en cinco de ellos. Un paciente fue homocigoto para c.35delG; otro resultó heterocigoto para c.35insG, mutación no reportada previamente; un tercero fue heterocigoto para c.34G>T y dos más fueron heterocigotos para el polimorfismo c.79G>A (p.V27I). En ningún caso se hallaron las mutaciones c.167delT y c.235delC. Conclusiones. Se encontraron cambios de secuencias que correspondieron a dos polimorfismos y a tres mutaciones. La frecuencia de las tres mutaciones investigadas fue menor a lo reportado en la literatura y se encontró una mutación no reportada previamente. Este estudio evidencia la importancia del diagnóstico oportuno con manejo integral, incluyendo el asesoramiento genético con base en estudios moleculares, y resalta la importancia de conocer el perfil genotípico de este grupo de pacientes.

Background. Congenital deafness is a public health problem affecting 2-3:1000 newborns in Mexico. Neonatal audiologic screening allows early detection with important implications for the functional prognosis. About 70% of cases of congenital deafness are associated with a genetic etiology with an autosomal recessive pattern of inheritance. Most cases are caused by mutations in the GJB2 gene, which codifies conexin 26. The three most commonly reported mutations in this gene are c.35delG, c.167delT and c.235delC. Methods. After obtaining informed consent, DNA was extracted from a blood sample, and the three previously mentioned mutations were searched for using PCR-RFLP or PCR followed by sequencing. Results. Molecular analysis was carried out in 11 patients. In five of these patients, a change in sequence was observed. In none of the patients were c.167delT and c.235delC mutations found. One patient was homozygous for c.35delG and another patient was heterozygous for c.35insG, which is a mutation not previously reported. A third patient was heterozygous for c.34G>T. Two additional patients had the c.79G>A (p.V27I) polymorphism. Conclusions. Frequency of the three mutations analyzed was lower compared to other populations. Five sequence changes were observed, two polymorphisms and three mutations, one of them novel. This study also demonstrates the relevance of early diagnosis and multidisciplinary management and the importance of determining the genetic basis of this disease in pediatric patients with congenital deafness.

Síndrome de Waardenburg: relato de casos / Waardenburg syndrome: case reports

JUSTIFICATIVA E OBJETIVOS: A síndrome de Waardenburg é uma doença genética que na forma clássica, os pacientes apresentam várias características físicas marcantes e também surdez neurossensorial. Assim, a partir da exposição dos casos espera-se que os profissionais de saúde tomem conhecimento da doença e possam levantar a hipótese diagnóstica diante de um pacientecom fenótipo sugestivo, tendo em vista que possui baixa frequência na população e seu diagnóstico precoce melhora muito a qualidade de vida dos pacientes.RELATO DOS CASOS: Trata-se de três casos dentro de uma mesma família com características diferentes, inclusive, em relação à surdez genética. Características marcantes estão presentes nos casos, como: dystopia canthorum, epicanto, base nasal proeminente e alargada, maxila encurtada, poliose, encanecimento precoce e surdez congênita neurossensorial. CONCLUSÃO: A grande maioria dos casos desta síndrome é acompanhada de surdez congênita. As características físicas que acompanham a doença permitem o seu diagnóstico clínico, e o ideal seria que esses pacientes fossem diagnosticados ainda na infância para que possam ter acesso precocemente à reabilitação auditiva, contribuindo para melhor desenvolvimento neuropsíquico, levando-se em conta que eles também deverão receber aconselhamento genético.

BACKGROUND AND OBJECTIVES: Waardenburg syndrome is a rare genetic disease that shows variable penetrance and expressivity. In its classic form, patients have several outstanding characteristics, such as deafness. Thus, from the exposure of cases, it is important to be aware of this clinical disease, to health professionals, for early diagnosis, avoiding unnecessary examinations, and achieving effective therapeutic approach.CASE REPORTS: These are three cases in one family with different characteristics, including in relation to genetic deafness. Striking features are present in cases like: dystopia canthorum, epicanthus, prominent and broad nasal base, shortened jaw, poliosis, premature graying and congenital sensorineural deafness. CONCLUSION: Most cases of this syndrome is accompanied by congenital deafness. Therefore, early diagnosis will certainly help in hearing rehabilitation, improving the capacity of developing hearing and communication skills of these individuals.