Learning disabilities in children with hearing loss: A systematic review.

PURPOSE: The main aim of this systematic review was to investigate the possible association between hearing loss [and/or history of otitis media with effusion (OME)] and learning difficulties in children. Secondary aims were to: (i) investigate if deaf and hard of hearing (DHH) children with learning difficulties might show different clinical and neuropsychological features compared with those with other neurodevelopmental disorders; (ii) identify possible predictors of learning difficulty in DHH children. METHODS: A review was conducted of the scientific literature reported by Pubmed, Cochrane and Scopus databases. The following inclusion criteria were used: (i) studies published after 2000; (ii) studies conducted considering subjects with age < 18 years; (iii) studies considering patients who showed both learning difficulties and hearing loss and/or episodes of OME; (iv) articles written in English. The exclusion criteria were: (i) presence in the studied cohort of any other proven comorbidities, other than hearing loss and/or OME; (ii) non-original studies. RESULTS: A total of 924 studies were identified. Four were reviewed after applying the above criteria. From their analysis it emerged that: (i) children with hearing loss who had undergone a diagnostic and rehabilitation program before 6 months of age had better levels of K readiness and language and literacy skills compared to those who had undergone it after 6 months; (ii) higher frequency of episodes of OME and the presence of a conductive hearing loss during the period of language acquisition was associated to lower scores in reading skills; (iii) reading difficulties found in subjects with hearing loss had similar characteristics to those with language difficulties. CONCLUSIONS: There is a dearth of information about this topic. Further investigations are therefore necessary on children of various ages with hearing loss to disclose learning difficulties in reading and writing abilities using current diagnostic tools.

Prognostic Factors in Idiopathic Sudden Sensorineural Hearing Loss: The Experience of Two Audiology Tertiary Referral Centres.

Background and Objectives: Although different hypotheses have been proposed over time, there is a dearth of information on factors able to predict the response to treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) and hearing recovery. The aim of this study was to apply univariate and multivariate statistical models in a retrospective clinical setting of patients given therapy for ISSNHL at our tertiary academic audiological centers to investigate the prognostic value of clinical signs, symptoms, and comorbidities in relation to hearing recovery. Materials and Methods: The inclusion criteria were: history of ISSNHL diagnosed and treated at the Padova or Modena tertiary academic audiological centers; age ≥ 18 years; availability of clinical and audiological outcome data. The exclusion criteria were: hearing loss in acoustic schwannoma, endolymphatic hydrops, meningitis, trauma (head trauma, temporal bone fracture, acoustic trauma), barotrauma, perilymphatic fistula; exposure to noise levels ≥ 80 dB in the work environment; any unilateral or bilateral hearing loss (except for presbycusis) prior to ISSNHL diagnosis; any disorders affecting the external or middle ear; any previous ear surgery; refusal to make medical data available for research purposes. Eighty-six consecutive patients (38 females, 48 males; median age: 58 years; interquartile range: 47.00-69.00 years) were included. A systemic steroid therapy was administered to all patients, either orally with prednisone or intravenously with methylprednisolone. Second-line therapy included intratympanic steroid injections and/or hyperbaric oxygen therapy. Results: A multivariate logistic regression model was used, including the non-multicollinear clinical and audiological variables, which showed a p-value < 0.10 at the univariate analyses (namely age at diagnosis, time to diagnosis, oral steroid dose, and PTA on the affected side). Only PTA on the affected side retained its statistical significance (OR: 1.0615, 95% CI: 1.0185-1.1063, p = 0.005). Conclusions: The analysis of our data showed an association between the hearing threshold before treatment and the recovery from ISSNHL. Further studies on larger cohorts (especially in a prospective setting) are needed to shed more light on the prognostic role of clinical parameters in patients with ISSNHL. In a correct counseling setting, with regard to the patient's concern about not being able to recover hearing, it is important to offer perspectives of appropriate hearing rehabilitation approaches.

Development of a New Self-Assessment Tool for Laryngopharyngeal Reflux Screening in Singers (SVHI-12-LPR).

INTRODUCTION: The present study aimed to develop a new tool for the evaluation of singers with self-reported symptoms suggestive of laryngopharyngeal reflux (LPR) (the SVHI-12-LPR), by correlating RSI with SVHI in a population sample of 163 subjects (both professional and amateur singers), evaluated also by videolaryngostroboscopy. This study was a cross-sectional, double-observational study. METHODS: RSI and SVHI were administered to 159 singers (amateurs, singing students, and professional singers). All subjects underwent videolaryngostroboscopy to objectively identify four subgroups: normal subjects (41.5%), subjects with organic lesions occupying the glottic space (17.6%), subjects with functional dysphonia (18.2%), and subjects presenting solely signs suggestive of LPR (22.6%). Using the validated RSI threshold, 33.9% of participants presented an RSI total score >13, suggestive of LPR. RESULTS: Subjects with a suspected diagnosis of LPR at videolaryngostroboscopy presented a mean RSI significantly higher than other subgroups (p < 0.001). Moreover, the SVHI-36 score did not statistically differ between pathological subgroups. A significant positive relationship was observed between RSI and SVHI total score (Spearman's rank correlation coefficient [ρ] = 0.474, p < 0.001). 12 SVHI items (items 1, 2, 4, 5, 6, 7, 12, 20, 24, 25, 26, 30) showed a significant association with RSI pathology classification. Statistical analysis demonstrated for the 12 selected items (SVHI-12-LPR) acceptable specificity (0.691) and sensibility (0.833) for the suspected diagnosis of LPR with a cut-off of 15. CONCLUSIONS: From the SVHI-36, 12 items were extracted that correlated with the specific impact that LPR has on the singer's voice (SVHI-12-LPR), as evaluated by RSI and videolaryngostroboscopy. Such questionnaire represents a new tool that could be applied to singers with symptoms suggestive of LPR to select which patients would benefit from a further phoniatric and videolaryngostroboscopic evaluation.

The Role of Primary Mitochondrial Disorders in Hearing Impairment: An Overview.

Background. Defects of mitochondrial DNA (mtDNA) involved in the function of the mitochondrial electron transport chain can result in primary mitochondrial diseases (PMDs). Various features can influence the phenotypes of different PMDs, with relevant consequences on clinical presentation, including the presence of hearing impairment. This paper aims to describe the hearing loss related to different PMDs, and when possible, their phenotype. Methods. A systematic review was performed according to PRISMA guidelines, searching Medline until December 2022. A total of 485 papers were identified, and based on specified criteria, 7 were included in this study. Results. A total of 759 patients affected by PMDs and hearing loss were included. The age of patients ranged from 2 days to 78 years old, and the male-to-female ratio was 1.3:1. The percentage of subjects affected by hearing loss was 40.8%, (310/759), and in most cases, hearing impairment was described as sensorineural, bilateral, symmetrical, and progressive, with different presentations depending on age and syndrome severity. Conclusions. PMDs are challenging conditions with different clinical phenotypes. Hearing loss, especially when bilateral and progressive, may represent a red flag; its association with other systemic disorders (particularly neuromuscular, ocular, and endocrine) should alert clinicians, and confirmation via genetic testing is mandatory nowadays.

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

Production of third-person direct object clitics in children with cochlear implants speaking Italian.

Previous research has shown that the production of third-person singular accusative object clitics (3DO clitics) might be taxing in Italian-speaking pre-school children with cochlear implants (CIs). We investigated this topic by assessing 3DO clitic production in 14 children with an average age of 8 years, who had received CI between age 1 and 4. The first goal of the study was to analyze whether school-aged children with CIs exhibit atypical behavior in 3DO clitic production. The second goal was to analyze whether children with CIs are prone to agreement errors in case of gender mismatch between the subject and the 3DO clitic, as has been shown for normal-hearing, typically developing children. To achieve this, we used two tasks in which subject and object clitic grammatical genders were manipulated so that they would or would not match. As for the first goal, the majority of children with CIs had good performance on the clitic tasks. However, some participants' performance was poor. The pattern of deviant responses differed among the poor performers. We believe that children with CIs showing impairments in 3DO clitic production need careful individual analysis in order to plan effective speech therapy. As for the second goal, children with CIs were more prone to agreement errors in the mismatch condition compared to the match condition; this dimension needs to be considered when assessing and eventually rehabilitating clitic production.

A panel of jitter/shimmer may identify functional dysphonia at risk of failure after speech therapy.

BACKGROUND: There are no reliable outcome predictors for functional dysphonia (FD) patients. OBJECTIVES: To investigate if any clinical or phoniatric characteristics could identify FD patients at risk of negative outcome after speech therapy. METHODS: We retrospectively reviewed the results of 78 FD patients treated with the proprioceptive elastic method. Before and one-month after therapy, patients underwent endoscopy, acoustic analysis with Multi-Dimensional Voice Program, and Voice Handicap Index-10 questionnaire (VHI-10). Negative outcome was the persistence of VHI-10 ≥ 13. RESULTS: 26 FD patients had negative outcome (i.e. VHI-10 ≥ 13) after speech therapy. At univariate analysis, clinical variables (i.e. sex, age, comorbidities, dysphonia duration, and professional voice use) were not associated with the outcome. Elevated Jitter% (Jitt; p = 0.03), Shimmer% (Shim; statistical trend, p = 0.06), and Noise to Harmonics Ratio (statistical trend, p = 0.06) were found in patients with poor results. At multivariate analysis, higher Jitt was an independent negative prognostic factor (p = 0.02), while a statically trend was identified for Shim (p = 0.06). A panel of Jitt >1.5 and Shim >5.1 showed an acceptable discriminatory power (AUC [ROC] = 0.76) according to Hosmer and Lemeshow scale. CONCLUSION: A panel of two acoustic analysis parameters could help in identifying FD patients at risk of speech therapy failure. Further studies in these patients are needed to evaluate the most efficient treatment protocol.

Quantification of scatter radiation from radiographic procedures in a neonatal intensive care unit.

BACKGROUND: In a neonatal intensive care unit (NICU), preterm infants are often exposed to a large number of radiographic examinations, which could cause adjacent neonates, family caregivers and staff members to be exposed to a dose amount due to scatter radiation. OBJECTIVE: To provide information on scatter radiation exposure levels in a NICU, to compare these values with the effective dose limits established by the European Union and to evaluate the effectiveness of radiation protection devices in this setting. MATERIALS AND METHODS: Radiation exposure levels due to scatter radiation were estimated by passive detectors (thermoluminescent dosimeters) and direct dosimetric measurements (with a dose rate meter); in the latter case, an angular map of the scatter dose distribution was achieved. RESULTS: The dose due to scatter radiation to staff in our setting is approximately 160 µSv/year, which is markedly lower than the effective dose limit for workers established by the European Union (20 mSv/year). The doses range between 0.012 and 0.095 µSv/radiograph. Considering a mean hospitalization period of 3 months and our NICU workload, the corresponding scatter radiation dose to an adjacent patient and/or his/her caregiver is at most 40 µSv. CONCLUSION: For distances greater than 1 m from the irradiation field, both scatter dose absorbed by a staff member during a year and that by an adjacent patient and/or his/her caregiver during hospitalization is less than 1 mSv, which is the exposure limit for public members in a year.

Robot-assisted procedures in pediatric neurosurgery.

OBJECTIVE During the last 3 decades, robotic technology has rapidly spread across several surgical fields due to the continuous evolution of its versatility, stability, dexterity, and haptic properties. Neurosurgery pioneered the development of robotics, with the aim of improving the quality of several procedures requiring a high degree of accuracy and safety. Moreover, robot-guided approaches are of special interest in pediatric patients, who often have altered anatomy and challenging relationships between the diseased and eloquent structures. Nevertheless, the use of robots has been rarely reported in children. In this work, the authors describe their experience using the ROSA device (Robotized Stereotactic Assistant) in the neurosurgical management of a pediatric population. METHODS Between 2011 and 2016, 116 children underwent ROSA-assisted procedures for a variety of diseases (epilepsy, brain tumors, intra- or extraventricular and tumor cysts, obstructive hydrocephalus, and movement and behavioral disorders). Each patient received accurate preoperative planning of optimal trajectories, intraoperative frameless registration, surgical treatment using specific instruments held by the robotic arm, and postoperative CT or MR imaging. RESULTS The authors performed 128 consecutive surgeries, including implantation of 386 electrodes for stereo-electroencephalography (36 procedures), neuroendoscopy (42 procedures), stereotactic biopsy (26 procedures), pallidotomy (12 procedures), shunt placement (6 procedures), deep brain stimulation procedures (3 procedures), and stereotactic cyst aspiration (3 procedures). For each procedure, the authors analyzed and discussed accuracy, timing, and complications. CONCLUSIONS To the best their knowledge, the authors present the largest reported series of pediatric neurosurgical cases assisted by robotic support. The ROSA system provided improved safety and feasibility of minimally invasive approaches, thus optimizing the surgical result, while minimizing postoperative morbidity.

Radiation exposure in diagnostic imaging: wisdom and prudence, but still a lot to understand.

Since 2000, a series of scientific articles on CT have been raising increasing concern about the risk of radiation induced cancer in children. The alarming conclusions of some of these articles had international echo through global media, provoking widespread public concern. Actually, many of these alarming scientific publications appeared to be flawed by poor study design, but their conclusions were not openly contradicted. In US and Europe pediatric radiologists had to face a huge challenge, which brought to the Image Gently campaign and the Eurosafe initiative with the aim to rebut misinformation and to support medical radiation protection. The Linear No Threshold model-which is the base of contemporary radioprotection-is increasingly questioned by new recent studies suggesting that low dose radiation would decrease cancer risk thanks to the enhancement of immune system response. Actually, pediatric radiologists have to cope with many important issues and contradictory messages. Good medical practice includes good communication about the benefits and risks of health procedures, thus the communication of radiation risk is a key component for radiologists. When considering benefits and risks, an important risk is too often ignored: the risk that skipping a diagnostic exam may cause a misdiagnosis, and therefore, a poor outcome. We should emphasize that a risk from a radiological investigation is very small, if a risk at all, and we are not sure that there is a risk at very low doses, like those doses in the majority of X-ray procedures including CT.

Stapes malformations: the contribute of the endoscopy for diagnosis and surgery.

The aim of this study is to investigate the contribute of the endoscopic exclusive transcanalar approach for the management of stapes malformations. A retrospective chart review was made at our tertiary referral centers. 17 patients with stapes malformations underwent surgery with endoscopic exclusive transcanal approach. A complete audiological and radiological assessment before and after surgery was performed. 12/17 (70 %) underwent a surgical endoscopic correction, In case of fixed platina underwent five endoscopic stapedotomy and one endoscopic stapedectomy were performed. In case of mobile platina five endoscopic ossiculoplasties with partial ossiculoplasty replacement prosthesis were performed, 3 with autologous remodeling incus and 2 with malleus head remodeling. In 1 case, only an endoscopic stapes mobilization was made. In 5/17 (30 %), due to difficult anatomical findings an endoscopic explorative tympanotomy was finally performed. The mean preoperative air conduction (AC), bone conduction (BC) and air-bone gap (ABG) were, respectively, 60.7, 26.3 and 34.4 dB. The mean postoperative AC, BC and ABG were, respectively, 33.8, 26.5 and 7.3 dB, with a mean improvement of the ABG of 27.1 dB. Discharge from hospital was on the first post-surgery day. No relevant postoperative complications were noted. The median follow-up was 3.6 years (range 1-6). The endoscopic approach results very adequate for the diagnosis and treatment of stapes malformations, checking variations of the ossicles conformation and functioning and performing safe surgery, under direct control of middle ear structures.

The production of direct object clitics in pre-school- and primary school-aged children with specific language impairments.

Third-person direct object (DO) clitic pronoun production is examined through an elicited production method in pre-school- and primary school-aged groups of Italian children with specific language impairment (SLI) to establish whether there is an improvement from age 5 years to age 7 years and whether there are qualitative differences in the two groups' responses. It was found that 5- and 7-year-old Italian children with SLI produce fewer third-person DO clitics than same-age peers. The kind of responses they provide changes: at 5 years, children with SLI tend to omit clitics, while at 7 years, they use a full noun. Production of third-person DO clitics is a persistent challenge for children with SLI and is confirmed to be a good clinical marker both at 5 and 7 years of age.

An optically coupled sensor for the measurement of currents induced by MRI gradient fields into endocardial leads.

OBJECT: The gradient fields generated during magnetic resonance imaging (MRI) procedures have the potential to induce electrical current on implanted endocardial leads. Whether this current can result in undesired cardiac stimulation is unknown. MATERIALS AND METHODS: This paper provides a detailed description of how to construct an optically coupled sensor for the measurement of gradient-field-induced currents into endocardial leads. The system is based on a microcontroller that works as analog-to-digital converter and sends the current signal acquired from the lead to an optical high-speed, light-emitting diode transmitter. A plastic fiber guides the light outside the MRI chamber to a photodiode receiver and then to an acquisition board connected to a PC laptop. RESULTS: The performance of the system has been characterized in terms of power consumption (8 mA on average), sampling frequency (20.5 kHz), measurement range (-12.8 to 10.3 mA) and resolution (22.6 µA). Results inside a 3 T MRI scanner are also presented. CONCLUSIONS: The detailed description of the current sensor could permit more standardized study of MRI gradient current induction in pacemaker systems. Results show the potential of gradient currents to affect the pacemaker capability of triggering a heartbeat, by modifying the overall energy delivered by the stimulator.

Endoscopic assisted cochlear implants in ear malformations.

The aim of present study is to describe the use of the endoscopic assisted cochlear implant approach in cases with severely malformed temporal bones and with anomalous anatomy of the inner ear and tympanic cavity. Eight patients with malformed middle and inner ear and bilateral profound hearing loss were operated using an endoscopic assisted cochlear implant procedure at our tertiary university referral center between January and September 2013. Five patients received a cochlear implant using a suprameatal endoscopic assisted approach. A chart review of clinical data and videos from the operations was performed. All procedures were re-analyzed and codified. In all patients, discharge from hospital was on the third day post-surgery. No immediate or late postoperative complications were noted. The current mean follow-up is 6 months, with range between 4 and 12 months. This approach proved to be successful in cochlear implant placement. It guaranteed a very good control on the facial nerve, even in cases with difficult anatomical conditions, mainly thanks to the endoscopic procedure. It also permitted an appropriate anatomical orientation of the abnormal middle ear with a direct safe cochleostomy, when the round window position would have been difficult to treat using a traditional approach.

Vertigo "in the pink": The impact of female gender on psychiatric-psychosomatic comorbidity in benign paroxysmal positional vertigo patients.

BACKGROUND: Comorbidity between vestibular and psychiatric disorders in predisposed individuals is underestimated, untreated, and may result in chronicization and poor quality of life. There are few studies concerning the type and the prevalence of psychiatric-psychosomatic distress in patients with benign paroxysmal positional vertigo (BPPV). OBJECTIVE: The aim of this study was to evaluate psychiatric-psychosomatic comorbidities, in particular anxiety, depression, somatization symptoms, and alexithymia, in a group of BPPV patients compared with healthy subjects, and according to gender. METHODS: Case-control study comparing 92 BPPV patients recruited at the ENT Unit of Modena General Hospital between November 2007 and December 2010, and 141 healthy controls. The Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Diagnostic Criteria for Psychosomatic Research (DCPR), Brief Symptom Inventory (BSI), and Toronto Alexithymia Scale (TAS-20) were used to perform psychometric assessment. RESULTS: BPPV patients scored higher than controls, with statistical significance, at BDI, BSI somatization, anxiety, and phobic anxiety subscales, and STAI state anxiety; a larger proportion of BPPV patients suffered from clinically significant BDI depressive symptomatology; DCPR disease phobia, functional somatic symptoms secondary to a psychiatric disorder, and demoralization were more common among BPPV subjects. High levels of symptomatology were still found among BPPV female patients, but not among males, even after controlling for symptom severity. CONCLUSIONS: Affective symptomatology, such as depression, demoralization, phobia and anxiety, and somatization, were significantly prevalent in BPPV patients, and female gender may be a predisposing factor.

Endoscopic cochlear implant procedure.

The objective was to asses the feasibility of the endoscopic technique for cochlear implant (CI) positioning avoiding mastoidectomy and to discuss the benefits and drawbacks of the technique. The study design is a surgical procedure description and prospective case series report. From December 2011 to October 2012, six patients underwent endoscopic CI. All cases were selected based on CT and MRI studies. All surgical steps were analyzed; intra-and post-operative complications were noted. The length of time for each surgical procedure was recorded. The surgical procedure was described step by step focusing on the anatomy of the round window (RW) niche, analyzing the critical point during the dissection. The timing of the surgical procedures was 120 ± 21 (mean ± SD) min. In 1/6 patients, intra-operative injury of the chorda tympani occurred. In all cases, an endoscopic identification was performed and the anatomical details of the RW niche were noted. In 6/6 cases, a RW niche magnification was performed endoscopically. 5/6 cases showed a normal conformation of the RW. In 1/6 patients, obliteration of the RW niche was found. In 4/6 patients, an endoscopic cochleostomy through the RW was performed. In 1/6 patients, a difficult insertion of the array was observed. The current follow-up is 7.3 months (SD ± 3.7). No post-operative short- or long-term complications were noted in this series. Endoscopic CI is a safe and viable technique with a low rate of complications and with good outcomes.

Auditory and Language Abilities in Children with Takenouchi-Kosaki Syndrome: A Systematic Review.

Takenouchi-Kosaki syndrome (TKS) is a rare congenital disease caused by a de novo mutation in the Cell Division Cycle 42 (CDC42) gene. Patients with TKS present facial and body dysmorphisms, hematologic and immune dysregulation, intellectual disability, neurodevelopmental delay and hearing loss. The aim of this study is to review the literature, focusing on hearing and language abilities in children with TKS. A systematic search on PubMed, Scopus and Web of Science databases was performed, including twelve studies for a total of 13 patients. Hearing loss (HL) occurs in a great percentage of patients (84.6%); nonetheless, auditory threshold, severity of HL and language abilities were reported in a few cases. In two studies, auditory rehabilitation strategies were described. Although several studies have investigated the hematological features of TKS, still only a few authors have focused on the audiological and language abilities of these children. Given the fact that HL has a significant impact on behaviors, communications skills, and quality of life, it is important to adequately assess and rehabilitate patients early with this syndrome. Further studies are needed to improve the knowledge about this topic and improve the quality of life of patients with TKS.

Unilateral Hearing Loss and Auditory Asymmetry in Mitochondrial Disease: A Scoping Review.

Background/Objectives: Mitochondrial transfer RNA mutations are one of the most important causes of hereditary hearing loss in humans. In most cases, its presentation is bilateral and symmetrical; however, there are numerous cases of single-sided presentation or asymmetrical onset described in the literature that may represent a diagnostic challenge. The aim of this review is to present the evidence of auditory asymmetry in mitochondrial diseases, highlighting the possible presence of cases with atypical presentation. Methods: A review of the English literature to date on hearing loss and mitochondrial diseases was performed using PubMed, Scopus, and Google Scholar databases. The literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for scoping review. Results: A total of 10 full-text articles were included in this review, comprising 25 patients with single-sided or asymmetrical hearing loss associated with mitochondrial disease. Conclusions: Sensorineural hearing loss due to mitochondrial disease can represent a complex diagnostic challenge in cases of asymmetric or unilateral presentation. It is critical to recognize this clinical variant and to diagnose it in daily clinical practice.

Audiological Phenotypes of Connexin Gene Mutation Patterns: A Glance at Different GJB2/GJB6 Gene Mutation Profiles.

GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles from a tertiary referral center in Northeastern Italy. We considered 57 patients with GJB2/GJB6 mutations presenting with congenital, non-syndromic SNHL, mainly coming from the Veneto region (Italy). The samples were screened for mutations in exons 1 and 2 of the GJB2 gene and for the GJB6 gene deletion del (GJB6-D13S1830). Free-field and air-conduction frequency-specific thresholds and the pure-tone average (PTA) were considered in the statistical analysis. Five patients (8.87%) had connexin gene mutations in simple heterozygosis, 15 (26.31%) in compound heterozygosis, 34 (59.64%) in homozygosis, and 3 (5.26%) with digenic patterns. The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy's largest-root test, p = 0.0473). Despite the evidence already available on genetic SNHL, many new insights are to be expected. Further large-scale prospective studies including different populations are necessary to confirm these preliminary findings about the clinical and audiological features of patients with different GJB2/GJB6 gene mutation patterns.

Conventional magnetic resonance imaging and diffusion tensor imaging studies in children with novel GPR56 mutations: further delineation of a cobblestone-like phenotype.

GPR56-related bilateral frontoparietal polymicrogyria (BFPP) is a rare recessively inherited disorder of neuronal migration caused by mutations of GPR56. To better delineate the clinical, molecular, and neuroradiological phenotypes associated with BFPP, we performed conventional magnetic resonance imaging and diffusion tensor imaging studies in a series of prospectively enrolled patients carrying novel GPR56 mutations. All subjects with GPR56-related BFPP showed a characteristic morphological pattern, including abnormalities of the cerebellar cortex with cerebellar cysts located at the periphery, a mildly thick corpus callosum, and a flat pons. Significant alterations of myelination and white matter tract abnormalities were documented. The present study confirms the phenotypic overlap between GPR56-related brain dysgenesis and other cobblestone-like syndromes and illustrates the contribution of 3D neuroimaging in the characterization of malformations of cortical development.