AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

Association of Autonomic Symptom Burden with Sudden Sensorineural Hearing Loss.

OBJECTIVE: To investigate the autonomic symptom burden in patients with sudden sensorineural hearing loss (SSNHL) and its association with the severity and prognosis. STUDY DESIGN: Observational prospective study. SETTING: Tertiary academic medical center. METHODS: Patients diagnosed with SSNHL at a single medical center completed the COMPASS 31 questionnaire, which assesses dysautonomia across 6 domains with 31 questions. A total COMPASS 31 score was calculated by summing the scores from each weighted domain. The treatment outcome was evaluated by the percentage of recovery, calculated as the hearing gain in pure tone average (PTA) after treatment divided by the pretreatment PTA difference between the 2 ears. We defined poor recovery as a percentage of recovery <80%. RESULTS: A total of 63 SSNHL patients were included. The mean COMPASS 31 score was 23.4 (SD 14). Patients with poor recovery had significantly higher COMPASS 31 scores than those with good recovery (mean 26.4 [SD 14.4] vs 16.9 [SD 10.4]; 95% confidence interval [CI] 2-17). There was a negative association between COMPASS 31 score and both hearing gain (r = -.323, 95% CI -0.082 to -0.529) and percentage of recovery (r = -.365, 95% CI -0.129 to -0.562). Multivariate analyses of independent factors indicate that patients with higher COMPASS 31 scores had a greater risk for poor recovery (OR 1.06 [95% CI 1.003-1.117]). CONCLUSION: This study highlights the association between autonomic symptom burden and poor hearing outcomes in SSNHL patients. The findings underscore the importance of evaluating autonomic function during the treatment of SSNHL.

Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose.

The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for clinical applications since they can cross the mesothelial cell layer and transduce inner hair cells (IHCs), although this requires relatively high doses. In this study, we investigated the effects of sucrose on the transduction of a variant of the AAV9 vector for gene transfer in the inner ear. We found that high concentrations of sucrose increased gene transduction in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. In addition, we demonstrated that simultaneous administration of sucrose enhanced the transduction of mouse IHCs and spiral ligament cells using an AAV9 variant vector. The procedure did not increase the thresholds in the auditory brainstem response, suggesting that sucrose had no adverse effect on auditory function. This versatile method may be valuable in the development of novel gene therapies for adult-onset sensorineural hearing loss.

Cochlear implant in tinnitus management.

PURPOSE OF REVIEW: To evaluate whether cochlear implantation can mitigate tinnitus perception and its discomfort among patients with severe-to-profound hearing loss, in order to provide an answer on a possible treatment for a health condition with high prevalence and impact on quality of life. RECENT FINDINGS: Tinnitus can develop after peripheral hearing loss and is associated with altered auditory processing. It does not only involve auditory structures but also aberrant neural activity and interaction with other regions of the Central Nervous System associated with emotion, attention, anguish, memory and motor activity. SUMMARY: Recent studies investigated the changes in tinnitus perception among patients who underwent cochlear implantation and demonstrated a postoperative decrease. Hence, patients with severe-to-profound sensorineural hearing loss and tinnitus are likely to benefit from cochlear implantation.

Regenerative Therapy Approaches and Encountered Problems in Sensorineural Hearing Loss.

Hearing loss is one of the most important public health matters worldwide, severely affecting people's social, psychological, and cognitive development. The perception of sound, movement, and balance in vertebrates depends on a special sensory organ called the cochlea, which contains hair cells and supporting cells in the inner ear. Genetic factors, epigenetics, the use of ototoxic drugs (some antibiotics and chemotherapeutics), noise, infections, or even aging can cause loss of hair cells and their related primary neurons, leading to sensorineural hearing loss. Although a sensorineural hearing loss, also known as permanent hearing loss, is treated with hearing aids and cochlear implants, treatment methods are limited. Since even the best implant cannot exhibit the characteristics of the original ear, the permanent sensory deficit will be permanent. For this reason, it has become important to develop regenerative treatment methods to regenerate and replace lost or damaged hair cells and neurons. Developments in stem cell technology have led to promising studies in regenerating damaged/lost hair cells or neurons with endogenous or exogenous cell-based therapies. Epigenetic mechanisms can turn hearing-related genes on and off and determine which proteins to copy. In addition, due to gene silencing, gene replacement, and CRISPR/CAS9 technology, gene therapy methods have accelerated, and studies have been carried out to treat dominant and recessive mutations that cause genetic-induced hearing loss or increase hair cell regeneration. In this paper, potential gene therapy and stem cell applications in the acquisition of cochlear function, which causes sensorineural hearing loss, and the difficulties encountered in these applications are compiled from a bioengineering perspective.

Spontaneous recovery rate of idiopathic sudden sensorineural hearing loss: A systematic review and meta-analysis.

PURPOSE: Steroids comprise the mainstay of treatment for idiopathic sudden sensorineural hearing loss (ISSNHL). Since steroidal treatment was integrated to clinical practice guidelines, newly published no-treatment or placebo arms in clinical trials are scarce. To evaluate the effectiveness of steroidal treatment ± hyperbaric oxygen therapy, the data should be compared to spontaneous recovery. The aim of this paper is to find the most accurate spontaneous recovery rate, in the light of which, other treatment modalities should be judged. MATERIALS AND METHODS: Eligible studies published until July 2021 were identified through systematic searches of 'PubMed', 'Web of Science' and 'Google Scholar'. Retrospective studies and randomised/non-randomised control trials involving only adult participants (≥18 years) with ISSNHL, and placebo/no treatment were included. Only articles that used the American Academy of Otolaryngology-Head and Neck Surgery's diagnostic criteria for ISSNHL were included. RESULTS: 942 records initially identified, 166 duplicates and 753 articles were excluded based on article subject, title, and abstract. The full texts of 13 articles were reviewed. Seven studies were included for qualitative synthesis, five papers included in quantitative synthesis. 180 ears were included in pooled statistics. The pooled spontaneous recovery was 60.28% (95% confidence interval [CI] = 38.88%-79.94%) with a heterogeneity of 86.0% (95% CI = 69.4%-93.6%). CONCLUSIONS: Spontaneous recovery of ISSNHL should not be over-looked, as it may be close to 60%. This may have both clinical and research implications.

Epidemiology of idiopathic sudden sensorineural hearing loss in the era of big data.

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a medical emergency, and delayed treatment can have permanent sequelae. However, the etiology of ISSNHL is diverse and unclear; thus, it is idiopathic. To develop an insight into this condition, patients with ISSNHL must be clearly identified. We propose an operational definition for the unambiguous identification of ISSNHL patients. Patients are identified through suggested definitions, and prevalence and general information are investigated. METHODS: A retrospective study of patients with ISSNHL was performed using the Health Insurance and Review Assessment-National Patient Sample from 2009 to 2016. To present a new operational definition, a systematic review was conducted for studies on ISSNHL from January 2007 to June 2021. After constructing several operant definitions using the conditions that can specify patients with ISSNHL in big data, we compared each definition to propose an operational definition. RESULTS: The important conditions required to classify patients with ISSNHL using big data were the International Classification of Diseases (ICD)-10 code, number of pure tone audiometry (PTA) tests, and whether steroids were prescribed. Among them, those who had undergone PTA tests more than twice could be clearly identified as patients with ISSNHL. CONCLUSION: As the use of big data becomes smoother, research using national medical data is being conducted; however, the results of the studies may vary depending on how a patient with ISSNHL is classified. Clear identification of patients with ISSNHL will be beneficial for better management of this condition.

Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice.

Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution. We delivered the PJVK transgene to the inner ear of Pjvk mutant mice using the synthetic Anc80L65 vector. We observed robust exogenous pejvakin expression in the hair cells and neurons of the cochlea and vestibular organs. Subsequent morphologic and audiologic studies demonstrated significant restoration of spiral ganglion neuron density and hair cells in the cochlea, along with partial recovery of sensorineural hearing impairment. In addition, we observed a recovery of vestibular ganglion neurons and balance function to WT levels. Our study demonstrates the utility of Anc80L65-mediated gene delivery in Pjvk mutant mice and provides insights into the potential of gene therapy for PJVK-related inner ear deficits.

Usos de cámara hiperbárica en otorrinolaringología / Uses for hyperbaric chambers in otolaryngology

Resumen En la terapia con oxígeno hiperbárico (HBO) se utiliza oxígeno al 100% de concentración en una cámara presurizada con presiones supraatmosféricas, que corresponden de 2 a 3 atmósferas. Los mecanismos por los cuales funciona esta terapia se relacionan con propiedades físicas de los gases y su comportamiento fisiológico en el organismo, lo que lleva finalmente a la hiperoxia, evento fisiológico que permite la obtención de diversos efectos beneficiosos. La evidencia en medicina ha demostrado su utilidad mayormente en la enfermedad por descompresión, infecciones cutáneas graves e intoxicación por monóxido de carbono. En el ámbito de la otorrinolaringología ha probado ser útil en algunas enfermedades como la hipoacusia súbita idiopática, tanto como terapia única como asociada al uso de corticosteroides, como en la osteomielitis refractaria del oído externo, la que en conjunto con antibioticoterapia y manejo quirúrgico presenta un evidente aumento en la tasa de mejoría. Cabe mencionar que la terapia con HBO ha demostrado también beneficios en los tratamientos y complicaciones posteriores a la radiación en pacientes con cáncer de cabeza y cuello. Es importante mencionar que la terapia con HBO no está exenta de riesgos y requiere que los pacientes cumplan con características específicas para su utilización, por lo que su indicación debe ser juiciosa y en casos seleccionados.

Abstract In hyperbaric oxygen therapy, 100% pure oxygen is used in a pressurized chamber with super atmospheric pressures which correspond to 2-3 atmospheres. The mechanism by which this treatment works is related to the physical properties of gases and their physiological behavior in the body, which leads to hyperoxia, the physiological event which allows for diverse beneficial health effects. The evidence in medicine has proven its utility mainly in decompression sickness, severe skin infections and carbon monoxide poisoning. In the otolaryngology field it has been proven useful in diseases like idiopathic sudden sensorineural hearing loss, both as the only treatment and as a concurrent treatment along with corticosteroids, in malignant otitis externa which in conjunction with antibiotic treatment and a surgical approach presents a clear increase in improvement rates. It must be mentioned that hyperbaric chamber treatment has also shown benefits in radiation treatment and post radiation complications in head and neck cancer patients. It is important to note that hyperbaric oxygen therapy is not without risks and patients must meet specific criteria for it to be applied, therefore it must be indicated using careful judgement and only in necessary cases.

Effect of constraint-induced music therapy in idiopathic sudden sensorineural hearing loss: A systematic review and meta-analysis.

Background: Idiopathic sudden sensorineural hearing loss (ISSNHL) is commonly encountered in audiologic and otolaryngologic practice. Constraint-induced music/sound therapy (CIMT) is characterized by the plugging of the normal ear (constraint) and the simultaneous, stimulation of the affected ear with music, which is based on a well-established neurorehabilitation approach. Corticosteroid therapy (CST) is the current mainstay of treatment. The prognosis for hearing recovery depends on many factors including the severity of hearing loss, age, and presence of vertigo. Objective: To analyze the effectiveness of CIMT with CST in ISSNHL. Methods: We performed a systematic search, using specific keywords relevant to our study, in PubMed, Cochrane Central Register of Controlled Trials, and additional sources of published trials till December 2020. We then screened all search results obtained according to our inclusion/exclusion criteria and performed a quality assessment on all studies using the Newcastle-Ottawa scale and using MedCalc, a meta-analysis was performed on suitable studies. Results: The recovery rates of three included nonrandomized studies were assessed at 1 to 3 months. A total of 229 (CST: 131, CST + CIMT: 98) patients were pooled for meta-analysis. The meta-analysis using the random-effect model found the relative risk of recovery rate within 3 months to be 1.213 (95% confidence interval 0.709-2.074), a result that is not statistically significant. Conclusion: Although our analysis results do not demonstrate the noticeable effect of CIMT in ISSNHL, it can support be a gainful adjunct to CST for better hearing results than CST alone. Therefore, it needs further prospective randomized controlled multicenter trials with a large sample.

[Advances in stem cell inner ear transplantation].

Sensorineural hearing loss has long been one of the common diseases in the field of otology. With the increasing research on stem cell therapy, the experiments and applications of stem cell inner ear transplantation are developing rapidly, with some remarkable results and some questions to be considered. The source of stem cells and the transplantation route are crucial, and the immune rejection in the post-transplantation period should not be ignored. This paper will review the issues related to stem cell source, transplantation route and immune rejection in inner ear transplantation, hoping to provide new ideas for research in the field of stem cell inner ear transplantation.

Hyperbaric Oxygen Therapy for Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

Importance: Sudden sensorineural hearing loss (SSNHL) is an acute, usually unilateral deficit. Systemic and intratympanic steroids are accepted treatments. Although evidence suggests that hyperbaric oxygen therapy (HBOT) may be beneficial, it is not widely offered. Objectives: To review and evaluate recent evidence of the association of HBOT with hearing outcomes in SSNHL and to determine if HBOT should be a single or part of a combination treatment regimen. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, Web of Science, CAB, ICTRP, Google Scholar, Clinicaltrials.gov, and ISRCTN databases were searched for randomized controlled trials (RCTs) published in English from January 1, 2000, and April 30, 2020. Study Selection: Prospective RCTs involving only adult participants (≥18 years) with SSNHL and comparing HBOT, as a single or combination therapy, with control therapies, such as steroids and/or placebo. Only RCTs that used the American Academy of Otolaryngology-Head and Neck Surgery's diagnostic criteria for SSNHL were included. Data Extraction and Synthesis: Data were extracted independently by 2 researchers. A fixed-effects model was used for analysis and performed from November 30, 2020, to May 20, 2021. Main Outcomes and Measures: The mean difference in absolute hearing gain recorded by pure-tone audiometric (PTA) thresholds averaged across 4 low (0.5, 1, 2, and 3 or 4 kHz) or 3 high (3 or 4, 6, and 8 kHz) frequencies was the primary outcome. The secondary outcomes were the odds ratio of hearing recovery defined as a hearing gain of ≥10 decibels (dB) in PTA average and treatment-related adverse effects. Results: Of the 826 records initially identified, 358 duplicates and 451 articles were excluded based on article type, title, and abstract. The full texts of 17 articles were reviewed, of which 14 were excluded because they were either not prospective RCTs (11 articles), the participants were less than 18 years old (2 articles), or the PTA was not reported at frequencies of interest (1 article). Three prospective RCTs with a total of 88 participants who received HBOT in the intervention groups and 62 participants who received only medical therapy in the control groups were studied. The intergroup difference in mean absolute hearing gain (mean difference, 10.3 dB; 95% CI, 6.5-14.1 dB; I2 = 0%) and the odds ratio of hearing recovery (4.3; 95% CI, 1.6-11.7; I2 = 0%) favored HBOT over the control therapy. Conclusions and Relevance: In this systematic review and meta-analysis, HBOT as part of a combination treatment was significantly associated with improved hearing outcomes in patients with SSNHL over control treatments. Trial Registration: PROSPERO Identifier: CRD42020193191.

Association of Bone Conduction Devices for Single-Sided Sensorineural Deafness With Quality of Life: A Systematic Review and Meta-analysis.

Importance: Although bone conduction devices (BCDs) have been shown to improve audiological outcomes of patients with single-sided sensorineural deafness (SSD), their effects on the patients' quality of life (QOL) are unclear. Objective: To investigate the association of BCDs on QOL in patients with SSD. Data Sources: Literature search of databases (Medline, Embase, Cochrane Library, and ClinicalTrials.gov) from January 1, 1978, to June 24, 2021, was performed. Study Selection: Prospective interventional studies with 10 or more participants with SSD (defined as pure tone average >70 dB hearing loss in the worse hearing ear and ≤30 dB in the better hearing ear) who underwent unilateral BCD implantation and assessment of QOL before and after the intervention using a validated tool were eligible for inclusion. Studies on adults and children were eligible for inclusion. Patients with only conductive, mixed, or bilateral hearing loss were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. Study clinical and demographic characteristics were obtained. Meta-analysis of mean differences in QOL scores before and after the intervention was performed. Study bias was assessed using Joanna Briggs Institute risk of bias tool. Main Outcomes and Measures: The main study outcome was mean change in QOL scores at 6 months after insertion of BCDs. The 3 QOL instruments used in the studies included the Abbreviated Profile of Hearing Aid Benefit (APHAB), the Health Utilities Index-3 (HUI-3), and the Speech, Spatial and Qualities of Hearing Scale (SSQ). The APHAB and the SSQ are the hearing-related QOL measures, whereas the HUI-3 is a generic QOL measure. Results: A total of 486 articles were identified, and 11 studies with 203 patients met the inclusion criteria. Only adult studies met inclusion criteria. Ten of 11 studies were nonrandomized cohort studies. The BCDs assessed were heterogeneous. There was a significant statistical and clinically meaningful improvement in the global APHAB scores (mean change, 15.50; 95% CI, 12.63-18.36; I2 = 0) and the SSQ hearing qualities (mean change, 1.19; 95% CI, 0.46-1.92; I2 = 78.4%), speech (mean change, 2.03; 95% CI, 1.68-2.37; I2 = 0), and spatial hearing (mean change, 1.51; 95% CI, 0.57-2.44; I2 = 81.1%) subscales. There was no significant change detected in the mean HUI-3 scores (mean change, 0.03; 95% CI, -0.04 to 0.10; I2 = 0). The risk of bias was assessed to be low to moderate. Conclusions and Relevance: These findings suggest that adult patients who receive BCDs may experience improvements in hearing-specific QOL measures but not in generic QOL measures. Prospective QOL studies should be considered in this cohort, particularly for children with SSD.

Combined Electric acoustic stimulation in a patient with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis.

There are few reports of the treatment for severe hearing loss due to otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV) achieved by cochlear implantation (CI). Here, we have reported the case of a patient with severe bilateral sensorineural hearing loss with low-frequency residual hearing by OMAAV. CI was performed in her right ear based on the results of contrast-enhanced magnetic resonance imaging (CE-MRI) and promontory stimulation test (PST). The residual hearing in her right ear was preserved after CI and utilized for combined electric acoustic stimulation (EAS). The combined EAS was used for 3 years until the residual hearing became stabilized. However, the usable hearing in low frequency worsened gradually, and the fitting strategy of cochlear implant was changed from combined EAS to CI alone 4 years after CI. Even when the speech discrimination score with CI no longer exceeds 50 %, the patient continued using CI because of its advantages in maintaining the quality of life of the patient. The combined EAS was found to be a feasible option even in an OMAAV patient with residual hearing. CE-MRI and PST may thus be helpful in deciding the side of CI surgery in a patient with OMAAV.

Differentiation capacity of dental pulp stem cell into inner ear hair cell using an in vitro assay: a preliminary step toward treating sensorineural hearing loss.

PURPOSE: Sensorineural hearing loss (SNHL) is commonly caused by the death or dysfunction of cochlear cell types as a result of their lack of regenerative capacity. However, regenerative medicine, such as stem cell therapy, has become a promising tool to cure many diseases, including hearing loss. In this study, we determined whether DPSCs could differentiate into cochlear hair cell in vitro. METHODS: DPSCs derived from human third molar dental pulp were induced into NSCs using a medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) for 7 days, and then into cochlear hair cell using a medium containing EGF and IGF-1 for the next 14 days. We used the neuroepithelial protein marker nestin and cochlear hair cell marker myosin VIIa as the markers for cells differentiation. Cells expressing the positive markers under the microscope were confirmed to have differentiated into cochlear hair cell. RESULTS: DPSCs were successfully induced to differentiate into NSCs, with mean 24% nestin-positive cells. We found that DPSC-derived NSCs have a great capacity in differentiating into inner ear hair cell-like cells with an average of 81% cells presenting myosin VIIa. Thus, DPSCs have high potential to serve as a good resource for SNHL treatment. CONCLUSION: We found the high potential of DPSCs to differentiate into NSC. The ability of DPSCs in differentiating into neural lineage cell made them a good candidate for regenerative therapy in neural diseases, such as SNHL.

Hipoacusia sensorioneural unilateral: Revisión de los manejos posibles en nuestra realidad nacional / Unilateral sensorineural hearing loss: Review of possible management in our national reality

La hipoacusia unilateral (HUL) definida como la pérdida auditiva de cualquier grado en un solo oído tiene prevalencias en edad escolar de 3% a 6%. La etiología es desconocida en la mayoría de los casos, pero destacan las anormalidades anatómicas severas a diferencia de las hipoacusias bilaterales, lo que le otorga importancia al estudio de imágenes. También se recomienda realizar evaluación oftalmológica. El impacto de la HUL se observa en la localización sonora, reconocimiento del habla, desarrollo del lenguaje, desempeño social y conducta, pero por sobre todo en el rendimiento académico. En este sentido es relevante mencionar que además de existir mayor probabilidad de repitencia de curso, es necesario mayor apoyo educacional individualizado para evitar dicha repitencia o lograr mismo éxito académico que un normoyente. En relación al diagnóstico aún faltan normas o protocolos, siendo éste un desafío en las zonas donde no hay screening universal. Se discute la importancia de las encuestas para realizar evaluaciones y seguimiento en estos casos. Finalmente se abordan las estrategias de intervención disponibles, además de un plan individualizado considerando al niño, su familia y sus expectativas, particularmente se discuten las características o factores a tomar en cuenta en el momento de la adaptación, para así lograr un tratamiento tendiente al éxito.

Unilateral hearing loss (UHL) defined as hearing loss of any degree in only one ear has a school-age prevalence of 3% to 6%. The etiology is unknown in most cases, but severe anatomical abnormalities stand out as opposed to bilateral hearing loss, which gives importance to the study of images. Ophthalmological evaluation is also recommended. The impact of UHL is observed in sound localization, speech recognition, language development, social performance and behavior, but above all in academic performance. In this sense, it is relevant to mention that in addition to having a higher probability of repeating the course, it is necessary to have more individualized educational support to avoid this repetition or achieve the same academic success as a normal listener. Regarding the diagnosis, there are still missing norms or protocols, this being a challenge in areas where there is no universal screening. The importance of surveys to carry out evaluations and follow-up in these cases is discussed. Finally, the available intervention strategies are discussed, in addition to an individualized plan considering the child, his family and his expectations, particularly, the factors to be taken into account at the time of adaptation, in order to achieve a success treatment.