Auditory Skills following Cochlear Implantation in Children with the Charge Syndrome.

OBJECTIVES: To assess the auditory outcomes and skills of pediatric cochlear implant (CI) users with the CHARGE syndrome. To determine the influence of inner ear malformations on the surgical procedure and speech understanding outcomes in this population. STUDY DESIGN: Observational, retrospective study. MATERIALS AND METHODS: Imaging, auditory testing, intraoperative findings, complications, and postoperative auditory skills and outcomes of pediatric CI users with CHARGE syndrome were recorded. RESULTS: 6 children (8 ears) were included, 5 of whom had prelingual deafness. Their mean age at implantation was 37 months. Six of the 8 ears presented cochlear malformation; the most frequent was hypoplasia type III. Intraoperatively, the transmastoid facial recess approach was used in 5 ears, and abnormalities of facial nerve anatomy were found in 5 ears. All electrode insertions were complete. All children were, to a varying degree, able to detect and identify sound. Verbalization skills were developed by 2 children, 1 of whom used oral language as his primary mode of communication. CONCLUSIONS: Cochlear implantation performed by an experienced surgeon in patients with the CHARGE syndrome is a safe procedure with adequate treatment planning. All children had improved auditory skills although the improvement was variable.

Atypical CHARGE associated with a novel frameshift mutation of CHD7 in a Chinese neonatal patient.

BACKGROUND: CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7, which has been estimated to occur in 1:10,000 births worldwide. It is a genetic disorder closely resembles other pattern of anomalies. Genetic testing should be pointed out as a useful method for clinical diagnosis. CASE PRESENTATION: A female infant was the second child born to a 33-year-old, gravida 3, para 2 mother. The infant was born at 37 + 4 weeks of gestation with a birth weight of 2440 g (- 1.1 S.D.). Clinical examination showed atypical CHARGE syndrome, with choanal atresia, a heart defect, and sensorineural deafness. Genomic DNA was extracted from peripheral venous blood sample using molecular biological technique. We used the Illumina TruSigt One sequencing panel on the MiSeq next- generation sequencing (NGS) platform for mutation screening and found a novel frameshift mutation in chromodomain helicase DNA binding protein 7 (CHD7; c.4656dupT). This mutation results in a new reading frame ending in p.(Ile1553fs). At the first month of age, the patient had a posterior nostril plasty operation by nasal endoscope. At the second month of age, she had patent ductus arteriosus ligation surgery. At the 4th month of age, she was discharged from the hospital. CONCLUSIONS: Our findings further reveal that patients should not be rejected for CHD7 mutational analysis even if they do not fulfill CHARGE syndrome Verloes criteria.

Cochlear implantation in children with CHARGE syndrome: a report of eight cases.

OBJECTIVE: To report neuroradiologic findings, surgical strategies and clinical and audiological results in a series of children with CHARGE syndrome (CS) who had been evaluated for cochlear implantation (CI). STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral university hospital. PATIENTS: Eight profoundly deafened children with CS were included. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre- and post-operatively. Neuroradiological and intraoperative findings, surgical planning, and post-operative complications were analyzed. RESULTS: Six children were profoundly deaf from birth and 2 had progressive hearing loss to profound levels. Cochlear nerve deficiency (CND) was noted in 5 out of the 6 patients with congenital sensorineural hearing loss (SNHL). Seven children underwent CI. Surgery was performed using standard transmastoid facial recess approach in 3 ears, subtotal petrosectomy in 3, and transmastoid single-slit labyrinthotomy in one. Temporary facial palsy occurred in one patient. In the group of patients with congenital SNHL, 2 children benefitted from CI and developed spoken language; the remaining 3 children obtained improved access to environmental sounds and used signs and gestures as their main mode of communication. The two patients with progressive SNHL had preoperative verbal language and continued to use verbal language after CI. CONCLUSIONS: The constant presence of temporal bone anomalies in children with CS requires surgical expertise in performing non-standard approaches for safe and effective CI. Patients with progressive SNHL and normal cochlear nerves had satisfactory results with CI. Limited benefits have been observed in presence of CND.

Oral features and computerized rehabilitation of a young patient with CHARGE syndrome using minimally invasive long-term interim CAD-CAM restorations.

Patients with CHARGE syndrome (where CHARGE stands for coloboma of the iris or retina, heart defects or cardiac malformations, atresia/stenosis of the choanae, retardation of growth and development, genital anomalies, and ear abnormalities) present several orofacial anomalies. Their treatment depends on the specific type of manifestation. To perform the complex oral rehabilitation and achieve a conservative, esthetic, and functional exploration of the definitive treatment goal, computer-aided design and computer-aided manufacturing (CAD-CAM) polymers can be used as long-term interim restorations. This article reports the treatment of a young patient with CHARGE syndrome combined with oral alterations. CAD-CAM polymers offer an intermediate treatment with satisfying esthetics and function at low biological cost until bone growth is completed. This period facilitates additional planning for the definitive restoration.

Cochlear implantation in children with "CHARGE syndrome": surgical options and outcomes.

CHARGE syndrome is a rare, polymalformative disease, representing one of the major causes of associated blindness and deafness. Bilateral, severe-profound, sensorineural hearing loss is common in CHARGE children. Aim of this study is to present our results in children with "CHARGE syndrome" submitted to cochlear implantation (CI). The frequency of anatomic anomalies, possible variations in the surgical technique of CI, and the audiological/rehabilitative benefits attained in our patients are reported. we submitted 5 children affected by CHARGE syndrome with profound, bilateral, sensorineural hearing loss to CI. Otoacoustic emissions, auditory brainstem response, acoustic impedance testing, cranial computed tomography and magnetic resonance were carried out preoperatively in all children. CI was performed using the mastoidotomy-posterior tympanotomy approach in two cases, and the suprameatal approach in three children. Infant toddler-meaningful auditory integration scale was used to evaluate kid's audiological performance before and after CI. Intra-operatory findings and postsurgical complications were evaluated. Among our patients, intraoperative anatomical malformations were cochlear hypoplasia (100 %), ossicles malformations (100 %), semicircular canals aplasia (100 %), oval window atresia (60 %), round window atresia (40 %), widening of the aqueduct of the vestibule (20 %), and aberrant course of the facial nerve (20 %). No intra- or postoperative complication was recorded in relation to implant positioning. After a follow-up ranging from 1 to 4.5 years, only 2/5 patients used oral language as the sole mean of communication, 1 started utilizing oral language as the main mean of communication, while 2 patients did not develop any linguistic ability. In conclusion, CI in patients with CHARGE association is feasible and, despite results variability, it should be carried out in CHARGE children with severe hearing loss as soon as possible. Although the selection of a specific surgical technique does not seem to influence the audiological outcome, the suprameatal access is valuable when important surgical landmarks (i.e. lateral semicircular canal and incus) are absent.

Clinical Portrait of Cochlear Implantation in Patients With CHARGE Syndrome.

OBJECTIVE: To examine the clinical characteristics and auditory performance of patients with CHARGE syndrome following cochlear implantation (CI), as well as the prognostic factors affecting auditory outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary academic center. METHODS: A retrospective chart review was performed in patients with CHARGE syndrome who underwent CI from 2007 to 2022. The category of auditory performance (CAP) score was used to assess the CI outcomes, and factors that may affect the speech outcomes were also evaluated. RESULTS: In 14 children with CHARGE syndrome, 22 CIs were performed, 6 unilaterally and 8 bilaterally. The mean age at CI was 25.9 months (range: 10-62). All patients had ear abnormalities and developmental delays, and cochlear nerve deficiency (CND) was present in all ears. At the last follow-up (mean: 49.6 months), the mean CAP score improved significantly compared to the preoperative measure (from 0.36 ± 0.81 to 3.21 ± 1.70, P = .001), with 6 patients (42.9%) achieving a CAP score of 4 points or higher. However, between the unilateral and bilateral CI groups, the final CAP score or change in CAP score was similar. Factors including age, coloboma, and CND did not significantly affect speech outcomes (all P > .05). CONCLUSION: Even though CHARGE syndrome features challenging anomalies, CI can be conducted safely and can offer effective contribution to significant speech improvement. Patients with CHARGE syndrome should be given the opportunity to undergo CI to maximize their audiological progress.

Cochlear Implant Outcomes in CHARGE Syndrome: Updated Perspectives.

OBJECTIVE: To evaluate outcomes of auditory implants in children with CHARGE syndrome and describe the evolution in management of hearing loss in this complex population. METHODS: A retrospective case review was performed at a tertiary referral center. Children with CHARGE syndrome who received either a cochlear implant (CI) or auditory brainstem implant (ABI) were included. Clinical records, demographic information, CHARGE features, neuroimaging, audiology, hearing rehabilitation interventions, operative notes, and outcomes were reviewed. RESULTS: Thirteen children with CHARGE syndrome underwent a total of 19 cochlear implants between 2008 and 2020. Among the congenitally deafened children (n = 9), six underwent bilateral implantation (five simultaneous and one sequential). Bilateral implantation was performed even in the presence of diminutive-appearing cochlear nerves. The average age of implantation was 1.1 years, and the mean device use time was 9.4 hours per day. Patients showed improvements in subjective family assessment related to hearing. In this group, two patients use oral communication, five use total communication, and two use sign language exclusively. Among the children with progressive hearing loss, the mean age of hearing deterioration was 4.4 years of age, and the device use time on average was 9.8 hours per day. The highest performer in the cohort was a child who lost hearing in their only hearing ear at age 4 and had normal cochleovestibular anatomy on that side. One child received an auditory brainstem implant at age two after deriving no benefit from a CI and can detect environmental sounds but is currently a nonuser. Over time, we noted that implantation occurred earlier in life and that practice has shifted toward bilateral implantation. CONCLUSIONS: Compared to a previous institutional cohort, children evaluated in this study were often implanted at a younger age and bilaterally with significantly improved outcomes. A CI evaluation should be considered in children with CHARGE syndrome to maximize sensory input and auditory ability.

[Perioperative management of cochlear implantation for CHARGE syndrome].

Objective:To explore the perioperative period characteristics of paediatric cochlear implant recipients of CHARGE syndrome with complex deformities. Methods:Retrospective case series of CHARGE syndrome were included. Radiological results, intraoperative findings, surgical planning and post-operative complications were analyzed. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre and post-operatively to measure auditory speech rehabilitation outcomes. Results:Five prelingual profoundly deaf children were identified, aged from 14 months to 60 months. All patients had congenital heart disease and underwent surgery before cochlear implantation. Upper airway abnormalities were detected as choanal atresia, laryngomalacia and tracheal stenosis. All ten ears showed cochlear abnormalities（Incomplete partition Ⅱ）, eight of them combined with secretory otitis media and/or middle ear deformity. All patients underwent single side surgery using standard transmastoid facial recess approach. Full insertion of the electrode was achieved in two cochleas, while partial insertion was done in three cochleas. Three ears with absent auditory nerves in MRI showed no response in the neural remote test. All patients had improved audio-speech performance with CAP scores 3.0±0.7 and 3.6±0.9, SIR scores 1.2±0.4 and 1.8±0.8, IT-MAIS scores 18.8±9.1 and 26.2±10.0, MUSS scores 2.2±2.4 and 7.2±8.3 after twelve months and twenty-four months follow up. Conclusion:Cochlear implantation in patients with CHARGE syndrome is a challenge in both its surgical and rehabilitation aspects due to multiple abnormalities. Adequate treatment planning is necessary for safe and effective surgery, including airway structures and intricate temporal bone landmarks.

[Cochlear implant and surgical intervention for CHARGE syndrome with laryngeal airway lesions].

Objective:To evaluate the clinical efficacy of surgical intervention for laryngeal airway lesions with concurrent cochlear implantation in CHARGE syndrome concomitant laryngeal airway lesions, and provide clinical data for cochlear implantation in children with CHARGE syndrome concomitant laryngeal airway lesions. Methods:The medical records of five cases diagnosed with CHARGE syndrome were retrospectively reviewed, two of them treated with surgical intervention for laryngeal airway lesions and concurrent cochlear implantation. One child treated with balloon dilatation of laryngeal stenosis and Cochlear implant, and another case received with modified supraglottoplasty for laryngeal malacia and Cochlear implant. Results:Two cases of CHARGE syndrome concomitant laryngeal airway disease, who underwent Cochlear implant and concurrent surgical intervention, recovered well after treatment. The remining three cases treated with Cochlear implant, who previously received deformity-correction surgery. All of the five cases presented with CHD7 mutation. Conclusion:Cochlear implant concurrent with surgical intervention of laryngeal airway lesions for the treatment of CHARGE syndrome concomitant laryngeal airway disease was safe and efficient, which could be a treatment option for children in this situation.

Diagnostics and therapy of bilateral choanal atresia in association with CHARGE syndrome.

BACKGROUND: Bilateral choanal atresia in patients with CHARGE syndrome becomes symptomatic immediately after birth. A prompt diagnosis, the implementation of sufficient preliminary measures, and the delivery of surgical therapy are crucial. This article is intended to assist in terms of diagnostics and a therapy recommendation. METHODS: We performed a retrospective study using the medical records of all newborns in the University Hospital in Bonn, diagnosed with bilateral choanal atresia and CHARGE syndrome and underwent surgery at the Department of Otorhinolaryngology, Head and Neck Surgery. RESULTS: A total of 21 patients have been treated with a unilateral or bilateral choanal atresia. 14 patients were primarily treated with transnasal endoscopy or underwent transnasal endoscopic surgery as a follow-up intervention (73.68%). Nine patients had a syndromal appearance, which was considered a definite diagnosis in six patients (five with CHARGE syndrome). All five patients with CHARGE syndrome received transnasal endoscopic treatment and a stent was inserted. DISCUSSION: Bilateral choanal atresia can be a life-threatening situation requiring acute measures. The therapeutic trend goes towards transnasal endoscopic resection. Primary intervention should be: minimally invasive, one-stage surgery, functional, and associated with low complication rates. Patency can be increased by saline irrigations, topical corticosteroids, endoscopic controls, and regular dilatation. The insertion of stents is controversially discussed but can be useful in syndromal patients. However, adjuvant therapy with a stent and mitomycin C is increasingly being abandoned. A significantly higher recurrence rate must be expected in association with CHARGE syndrome. Stenting should be considered on an individual basis. Continuous training and support of the parents are obligatory.

[Symptoms and treatment of choanal atresia--stenting remains controversial]. / Symptome und Therapie der Choanalatresie--Stents weiterhin umstritten.

Congenital choanal atresia is a rare malformation of the upper airways occurring sole or within the scope of syndromes. The controversy regarding standardized surgical approach and optimal technique preventing re-stenosis as well as the proceeding in case of a unilateral malformation persists. To address these issues, a retrospective analysis of patients presenting with choanal atresia in our department within the last 10 years was performed. 15 infants aged 3 days to 13 years (mean 42 months) who presented with unilateral (10 cases) and bilateral (5 cases) choanal atresia underwent surgical repair. 4 patients failed previous surgeries. All interventions were performed in transnasal endoscopic technique. 7 patients were intraoperatively stented for 6 weeks, 4 patients for 1 week. In 73% (11 out of 15 children) further congenital anomalies were identified. In 7 cases a re-stenosis requiring treatment occurred, predominantly in long-term stented patients. No intra- or postoperative hemorrhages or infections occurred. To provide an adequate work-up of affected patient including a screening for further congenital anomalies, a multidisciplinary approach is required. Endonasal endoscopic approach represents a safe technique for surgical repair of choanal atresia. The indication for surgical repair in case of a unilateral atresia is based on the severity of clinical symptoms. The use of stents, especially of long term, remains controversial and needs further evaluation.

CHARGE syndrome: genetic aspects and dental challenges, a review and case presentation.

BACKGROUND: CHARGE syndrome (CS) is a rare genetic condition (OMIM #214800). The condition has a variable phenotypic expression. Historically, the diagnosis of CHARGE syndrome was based on the presence of specific clinical criteria. The genetic aetiology of CS has since been elucidated and attributed to pathogenic variation in the CHD7 gene (OMIM 608892) at chromosome locus 8q12. CASE PRESENTATION: A South African female of mixed ancestry heritage, aged 4 years, was referred for dental assessment to the Faculty of Dentistry, University of the Western Cape, in 2018. She had a diagnosis of CHARGE syndrome confirmed by a Medical Geneticist from the Division of Molecular Biology and Human Genetics at the University of Stellenbosch. The patient had a long prior history of health and developmental problems, with the correct diagnosis becoming apparent over time. She presented with many oral and craniofacial features warranting consideration by the dentist including micrognathia, hypoplastic nasal bones, cranial nerve dysfunction, bruxism, craniofacial anomalies and compromised sensory perception. The treatment was mainly preventive and, although she fed through a percutaneous endoscopic gastrostomy tube (PEG), maintenance of her oral hygiene was necessitated. CONCLUSION: CS is a multisystem condition and the optimal care for an individual is with a specialist multidisciplinary team. The numerous systemic problems affecting these individuals take precedence in their care, and often there is neglect of their dental concerns. Given the abnormalities frequently present in the oral and craniofacial region, the authors recommend that a team of dental and other medical specialists be involved in the management of individuals with CS.

Modified transcanal cochlear implantation in CHARGE syndrome: A case report.

RATIONALE: Cochlear implantation (CI) in CHARGE syndrome is technically challenging because of the anatomical anomalies. This case aims to report a successful case of CI in CHARGE syndrome by using the modified transcanal approach with external auditory canal (EAC) obliteration. PATIENT CONCERNS: The 3-year-old girl presented at the outpatient department with bilateral hearing loss and nasal obstruction since birth. DIAGNOSIS: The patient had bilateral profound sensorineural hearing loss, patent ductus arteriosus, atresia of the choanae, middle and inner ear anomalies, and growth retardation, fulfilling the criteria for typical CHARGE syndrome. High resolution temporal bone computed tomography scan revealed a poorly developed mastoid cavity, cochlear dysplasia, hypoplastic semicircular canals, ossicular chain malformation, and sigmoid sinus engorgement. Magnetic resonance imaging revealed a narrow internal auditory canal and a hypoplastic cochlear nerve. INTERVENTIONS: Modified transcanal approach with external auditory canal obliteration OUTCOMES:: CI was successfully done and there are no intraoperative or postoperative complications occurred after 1 year of follow up. LESSONS: The modified transcanal approach is a reasonable and safer option for CI in CHARGE syndrome.

Special Populations in Implantable Auditory Devices: Developmentally Challenged and Additional Disabilities.

Children with hearing loss and additional disabilities can benefit from cochlear implants and other implantable auditory devices. Although each individual child must be evaluated, and families uniquely counseled on goals and realistic expectations, overall many gains and benefits are possible in this population. In this article, an overview of the considerations for this group is discussed and outcomes are reviewed, including auditory and speech measures as well as benefits in other skills and quality of life.

Systematic review of cochlear implantation in CHARGE syndrome.

Objective: CHARGE syndrome presents with a collection of congenital anomalies affecting multiple organs. Ear and temporal bone anomalies, including hearing loss are highly prevalent. We present an aid to management of this challenging condition and report the strategies and outcomes of cochlear implantation. Methods: Systematic review of Medline, EMBASE, Web of Science, CENTRAL and clinicaltrials.gov was performed up to 21/10/2018 The review and meta-analysis of studies were performed according to the PRISMA statement. Patient demographics, comorbidity, anatomical factors, details of cochlear implantation and audiological outcome were extracted and summarized. Anatomical and surgical factors were evaluated by meta-analysis. Audiological outcomes reported were too heterogeneous for meta-analysis. All statistics were calculated with SPSS v23.0 (IBM, New York, USA). Results: Thirty-one studies reported 165 cochlear implants in 156 patients with CHARGE syndrome. Temporal bone and facial nerve anomalies were common. Discussion: The assessment and management of patients with CHARGE syndrome undergoing cochlear implantation is challenging. Outcomes may be affected by cochlear nerve deficiency, inner ear anomalies, and developmental delay. Surgery is almost invariably complicated by abnormal anatomy, and increased incidence of complications. Conclusion: A careful, case-by-case assessment of an individual's requirements within a multi-disciplinary setup is essential for achieving the best possible outcome.

Surgical Palliation of Right Aortic Arch With an Isolated Innominate Artery From the Left Ductus Arteriosus.

A right aortic arch with an isolated left innominate artery from the left patent ductus arteriosus is a rare arch anomaly, and establishing continuity between the innominate artery and aorta can be challenging. We describe repair of this lesion in a three-week-old male using an autologous pedicle flap of ascending aorta as well as a homograft patch as the roof to recreate continuity between the aorta and left innominate artery.

Stentless mirrored L-shaped septonasal flap versus stented flapless technique for endoscopic endonasal repair of bilateral congenital choanal atresia: a prospective randomised controlled study.

OBJECTIVES: To compare the outcomes of endoscopic repair of bilateral congenital choanal atresia using a flap technique without stenting versus endoscopic repair using stenting without a flap. METHODS: A prospective randomised controlled study was conducted, comprising 72 patients with bilateral congenital choanal atresia. The patients were randomised into two groups. Group A (42 patients) underwent endoscopic repair using a mirrored L-shaped flap without stenting, and group B (30 patients) underwent endoscopic repair using stenting without a flap. RESULTS: At a mean follow-up period of 18.2 months, endoscopic assessment revealed a patent posterior choana in 81 per cent and 83.33 per cent of patients in group A and group B respectively. Choanal stenosis occurred in 21.40 per cent and 33.33 per cent of patients in group A and group B respectively. Granulation tissue was observed in 28.6 per cent and 53.3 per cent of patients in group A and group B respectively. CONCLUSION: The endoscopic approach utilising a flap without stenting is safe and effective, with a high success rate.

Skull base anatomy and surgical safety in isolated and CHARGE-associated bilateral choanal atresia.

INTRODUCTION: Bilateral choanal atresia (BCA) is associated with a high incidence of congenital abnormalities that include skull base anomalies and defects. Surgical repair of BCA is necessary in the early neonatal period and any altered anatomy of the adjacent skull base will heighten the risk of intracranial injury. This risk may be further increased in patients with CHARGE syndrome. OBJECTIVES: To measure surgically relevant nasal and skull base dimensions in neonates with BCA in order to determine whether any difference exists between isolated and CHARGE syndrome associated subgroups, thereby optimizing the safety of surgical repair. METHODS: A retrospective review of medical charts and computed tomography was undertaken at a tertiary pediatric hospital of all neonates diagnosed with BCA between 2004 and 2016. Isolated and CHARGE syndrome subgroups of BCA were identified from clinical records and CT data was analyzed and compared between the two. The skull base parameters measured were choanal width, choanal height, mid-nasal skull base height and skull base slope. RESULTS: Of the 13 patients included, 3 had CHARGE syndrome and 10 had isolated BCA. Whilst the difference in mid-nasal height approached significance for the two groups, numbers were too small for a statistical difference to be identified. The mean value for choanal width in the isolated BCA group was significantly less the largest series of normative data available in the literature for comparison (p < 0.001). No skull base anomalies were noted in either group. CONCLUSION: While this is a small study with limited numbers, it is the first that has attempted to identify and measure the posterior nasal and skull base anatomy most pertinent to avoiding skull base injury in the surgical management of BCA.