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.

The Study Of Hrct And Mri Temporal Bone Findings In Pediatric Patients With Congenital Sensorineural Hearing Loss

Introduction -The incidence of Congenital Sensorineural hearing loss (SNHL) is approximately 1: 1000 live births. SNHLis either due to disorders of the inner ear or cochleovestibular cranial nerve. Radiological evaluation is necessary to detect or rule out causes of SNHL. Also, the treatment of SNHLis predominantly determined by the etiology of hearing loss. Aim & objective-Radiological assessment of various congenital inner ear malformations in pediatric age group patients with sensorineural hearing loss in a tertiary care centre.Material & Methods-This is a prospective study conducted between 1 January 2018 and 1 June 2019 in Department of Radiodiagnosis, SAIMS, Indore & included all paediatric patients (93 children), who came for HRCTand MRI temporal bone imaging with the clinical diagnosis of congenital sensorineural hearing loss (SNHL) / for evaluating congenital sensorineural hearing loss (SNHL).Results-In our study out of 93 paediatric patients , no significant radiological abnormality were detected in 68 patients (73.11%), however, 25 patients (26.88%) had various congenital anomalies of the inner ear and vestibulocochlear nerve. Most commonly affected organ was cochlea. Among these 25 patients only cochlea was involved in 7(28%), both Cochlea and semicircular canal in 4(16%), and Cochlea and vestibular aqueduct in 1 patient(4%). Isolated vestibular aqueduct dilatation was found in 8 (32%) patients. Isolated semicircular canal involvement and cochleovestibular nerve abnormality were seen in 3 (12%) and 2 (8%) patients respectively.Conclusion-In this study, imaging has helped us to detect various inner ear malformations in children with congenital sensorineural hearing loss. It is helpful for preoperative planning and preparation for cochlear implant in a tertiary care centre

ANALYSIS ON CURRENT SITUATION OF PATIENTS WITH HEARING LOSS AND DEAFNESS / Шинэ санаа Шинэ нээлт

@#BACKGROUND Congenital and acquired hearing loss considered as the most common disability. According to the WHO report, 360 million people worldwide have disabling hearing loss, and 32 million of these are children. Severe to profound sensorineural hearing loss can be treated successfully with cochlear implants. Post implant Auditory Verbal Therapy/ Hearing Implant Rehabilitation is essential for the progress and better outcome. Multidisciplinary team approach, including ENT, audiologist, speech therapy, social worker, coordinator, caregiver /parent is required. The first clinical speech therapy department in Mongolia was established by the School of Dentistry, MNUMS based at the Maxillofacial Surgery Department of the MCNHC in 2006 (G. Ariuntuul, B. Bulgan, U. Azzaya). Where as the very first Cochlear Implanted child in Mongolia was received the surgery and audiology support by A. Ulziibayar, L. Byambasuren, B. Misheel, B. Narantya and the hearing implant rehabilitation treatment successfully conducted by the abovementioned speech team in 2009. Aim: To analyze current situation on speech therapy intervention for patients with hearing loss and deafness. METHODS Retrospective hospital data were collected based on the School of Dentistry, Speech therapy department between January, 2009- February, 2017. In total 70 patients’ information were retrieved for the study. Descriptive method is used for statistical analysis. RESULTS Out of 70 patients, attended speech therapy sessions 38 (54%) were males, 32 (46%) were females; where as 21 (30%) had congenital deafness and 28 (40%) acquired; 21 (30%) patients with hearing loss not known their causes of deafness. From the total of 28 (100%) cases with acquired hearing loss/deafness 11 (39%) patients cause of deafness is due to complication from infectios disease: meningitis.

Perioperative challenges in management of a deaf and dumb patient posted for high‑risk cardiac surgery.

Perioperative management of deaf and dumb patients can be a challenging task. For smooth postoperative recovery, proper care should begin in the preoperative period. Understanding the patients’ needs and training him to follow the instructions requires to involve a communication specialist. Judicious use of sedatives and analgesics is essential to keep the patient pain‑free and comfortable. Postoperatively, the patient should be kept awake, enough to understand the internal need of the body and to make a meaningful response to external stimuli. Adequate preoperative planning and coordinated team efforts with involvement of specialists can help in delivering better postoperative care.

Reduced Gray Matter Volume of Auditory Cortical and Subcortical Areas in Congenitally Deaf Adolescents: A Voxel-Based Morphometric Study

PURPOSE: Several morphometric studies have been performed to investigate brain abnormalities in congenitally deaf people. But no report exists concerning structural brain abnormalities in congenitally deaf adolescents. We evaluated the regional volume changes in gray matter (GM) using voxel-based morphometry (VBM) in congenitally deaf adolescents. MATERIALS AND METHODS: A VBM8 methodology was applied to the T1-weighted magnetic resonance imaging (MRI) scans of eight congenitally deaf adolescents (mean age, 15.6 years) and nine adolescents with normal hearing. All MRI scans were normalized to a template and then segmented, modulated, and smoothed. Smoothed GM data were tested statistically using analysis of covariance (controlled for age, gender, and intracranial cavity volume). RESULTS: The mean values of age, gender, total volumes of GM, and total intracranial volume did not differ between the two groups. In the auditory centers, the left anterior Heschl's gyrus and both inferior colliculi showed decreased regional GM volume in the congenitally deaf adolescents. The GM volumes of the lingual gyri, nuclei accumbens, and left posterior thalamic reticular nucleus in the midbrain were also decreased. CONCLUSIONS: The results of the present study suggest that early deprivation of auditory stimulation in congenitally deaf adolescents might have caused significant underdevelopment of the auditory cortex (left Heschl's gyrus), subcortical auditory structures (inferior colliculi), auditory gain controllers (nucleus accumbens and thalamic reticular nucleus), and multisensory integration areas (inferior colliculi and lingual gyri). These defects might be related to the absence of general auditory perception, the auditory gating system of thalamocortical transmission, and failure in the maturation of the auditory-to-limbic connection and the auditorysomatosensory-visual interconnection.

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.

Long QT syndrome in children with congenital deafness.

The Jervell and Lange-Nielson syndrome(JLN) is an infrequent form of long QT syndrome (LQTS) in which prolonged QT interval and congenital deafness exist together. We attempted to identify patients with LQTS among 127 children (age 1.2-10 years) with congenital hearing loss. The corrected QT interval was measured from 12 lead electrocardiogram(ECG) , using Bazette’s and Friedricia formulae.The QT interval was considered prolonged when it exceeded the upper limit of 440ms and 450ms, respectively. Ten children with congenital deafness had a corrected QT interval longer than 440ms. Although these children did not meet the definite criteria according to Schwartz parameters, all the 10 children could be defined as having intermediate probability of LQTS according to revised criteria. We advise that children with congenital deafness be screened for long QT syndrome .

Investigation of Developmental Changes of Convergence Ratios of MNTB-LSO Synapses in Circling Mice / 대한해부학회지

The developmental changes of convergence ratios of medial nucleus of trapezoid body (MNTB) axons to single lateral superior olive (LSO) neuron were investigated using voltage clamp technique in homologous (cir/cir) circling mice, animal model for the congenital deafness with autosomal recessive inheritance. As the developmental reduction of convergence ratio reported in rats indicates the presence of synaptic refinement, we aimed to find out whether the similar reduction of convergence ratio also occurs in circling mice. Heterologous (+/cir) mice were used as control and mice younger than postnatal (P) day 4 or older than P9 were used. The convergence ratios of MNTB axons to single LSO neuron were 29.16+/-2.7 (n=12, P9) in homologous (cir/cir) mice, while they were 37.89+/-3.8 (n=9, P9) in heterozygous (+/cir) mice. The significant changes were observed only in heterozygous (+/cir) mice, which indicated that synaptic refinement of MNTBLSO synapses occurs in heterozygous (+/cir) mice, not in homozygous (cir/cir) mice. Considering homologous (cir/cir) mice being animal model for the congenital deafness, our data might contribute to the understanding of developmental changes of brain stem auditory circuits of congenitally deaf patients.