Successful Cochlear Implantation in a Patient With Wolfram Syndrome Type 1: a case report

Successful Cochlear Implantation in a Patient With Wolfram Syndrome Type 1: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Successful Cochlear Implantation in a Patient With Wolfram Syndrome Type 1: a case report Fatemeh Sarv, Nasrin Asgari Soran, Saleh Mohebbi, Tahereh Zabihi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9646524/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Wolfram syndrome type 1 (DIDMOAD) is a rare autosomal recessive neurodegenerative disorder characterized by early-onset diabetes mellitus, optic atrophy, and progressive sensorineural hearing loss. Management of profound deafness in these patients is challenging, and outcomes of cochlear implantation remain variable. Case presentation We report a 23-year-old Iranian woman with genetically confirmed Wolfram syndrome type 1 who presented with poorly controlled diabetes, progressive visual impairment, and profound bilateral hearing loss refractory to hearing aids. Genetic testing revealed a homozygous frameshift variant in WFS1 , with both parents identified as heterozygous carriers. The patient underwent cochlear implantation without complications and achieved meaningful functional hearing, with marked improvement in communication and daily auditory perception. Conclusion This case demonstrates that cochlear implantation can provide substantial auditory benefit in selected patients with Wolfram syndrome and highlights the importance of early genetic diagnosis and multidisciplinary management. Wolfram syndrome DIDMOAD Cochlear implantation Sensorineural hearing loss Case report Figures Figure 1 Figure 2 Introduction Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal recessive neurodegenerative disorder most commonly caused by pathogenic variants in the WFS1 gene (1, 2). The condition typically presents in childhood with insulin-dependent diabetes mellitus and progressive optic atrophy, followed by multisystem neurologic and sensory deterioration during adolescence and early adulthood (3, 4). Although cochlear implantation outcomes in Wolfram syndrome are variable due to underlying neurodegeneration, selected patients may still achieve meaningful auditory benefit when cochlear nerve integrity is preserved (5–7). Given the rarity of Wolfram syndrome and the limited literature on auditory therapy, especially in Middle Eastern populations, reporting individual cases remains clinically valuable. We present a young woman with genetically confirmed Wolfram syndrome who underwent successful cochlear implantation with significant improvement in auditory perception and communication. This case underscores the importance of early referral, multidisciplinary management, and the role of cochlear implantation in selected patients. This manuscript conforms to the CARE guidelines for the reporting of case reports (8). Case presentation A 23-year-old Iranian woman with genetically confirmed Wolfram syndrome type 1 (DIDMOAD) was referred to our endocrinology clinic for poorly controlled diabetes mellitus. She had been diagnosed with diabetes at the age of two and had gradually developed progressive visual disability as well as severe bilateral sensorineural hearing loss during adolescence. In addition to long-standing diabetes mellitus, the patient had a documented history of central diabetes insipidus (DI) and was receiving desmopressin therapy at the time of presentation, completing the classic DIDMOAD phenotype. At presentation, she reported fatigue, polyuria, and distal paresthesia involving the plantar surface of the feet, suggestive of diabetic neuropathy. She was advised to use hearing aids since previous two years, however recently they were useless. On admission, laboratory evaluation showed markedly elevated fasting blood glucose (312 mg/dL), HbA1c of 9.5%, and elevated two-hour postprandial glucose (234 mg/dL). Her insulin regimen was therefore adjusted by increasing the basal dose and recalculating pre-meal boluses based on carbohydrate intake. She received advise on glucose monitoring, diet, and foot care, and was scheduled for close endocrinology follow-up. Although the family initially reported no other affected members, genetic testing showed that both parents were heterozygous carriers of the WFS1 c.547del pathogenic variant, while the proband was homozygous. This finding confirmed the autosomal recessive inheritance pattern, and a pedigree was created to show carrier status within the family (Fig. 1). Because of her disabling hearing loss and low hearing aids positive effect, the patient was evaluated for cochlear implantation in our ENT department. Pre-operative audiological assessment showed no functional residual hearing, Speech recognition was less than 50 percent in both ears and no significant benefit from amplification. She was candidate to ipsilateral cochleal implantation. Temporal bone Computed Tomography (CT) scan was normal. The ENT committee has choose Advanced Bionic HiRes Ultra 3D/ HiFocus SlimJ with Nida CI Q90 Processor to implant. She was admitted to stabilized general condition and blood sauger pre-operatively and underwent cochlear implantation. The procedure was performed through a standard transmastoid posterior tympanotomy approach. The round window was exposed, and the electrode was smoothly inserted without resistance. Intraoperative neural response and impedance testing showed appropriate function of all sixteen electrodes, and no surgical complications were encountered. Initial device activation occurred three weeks after surgery. Post-operative programming showed stable stimulation thresholds across the array. Electrically-evoked Compound Action Potential (ECAP) response was present. Neural Response Telemetry (NRT) value correlate with patient behavioral map. Impedance testing at activation confirmed normal electrical function of all sixteen electrodes, with values remaining stable over subsequent follow-ups (Fig. 2). After nine months, the patient was satisfied and experienced progressive improvement in auditory perception. Although exact audiometric thresholds varied across visits, she repeatedly achieved meaningful access to conversational-level speech. Qualitatively, she reported being able to detect everyday environmental sounds, recognize familiar voices, and communicate effectively in quiet settings, abilities that were absent prior to implantation. The Cochlear Implant Quality of Life questionnaire (CIQOL-10) was administered to further assess postoperative outcomes. The patient continues multidisciplinary follow-up. Endocrinology manages her diabetes and neuropathic symptoms, ophthalmology monitors progressive optic atrophy, and audiology provides ongoing device programming and auditory rehabilitation. Speech therapy sessions focus on improving speech perception and communication strategies. Genetic counseling was provided to the patient and her family regarding the autosomal recessive inheritance pattern and future reproductive considerations. Despite the progressive neurodegenerative nature of Wolfram syndrome, cochlear implantation in this case restored functional hearing and substantially improved the patient’s communication abilities and overall quality of life. Discussion This case represents a classic phenotype of WS1, supported by molecular confirmation of a homozygous WFS1 frameshift variant. Identification of heterozygous carrier status in both parents and construction of a pedigree further reinforce the autosomal recessive inheritance pattern. Studies across the WS1 range highlight substantial phenotypic variability among individuals with WFS1 mutations, with ophthalmic, neurologic, and psychiatric manifestations differing significantly even among related carriers (9). These findings are consistent with our patient’s combination of progressive visual decline, severe auditory dysfunction, and long-standing metabolic disease. From an audiologic and otologic perspective, the successful cochlear implantation in our patient is clinically meaningful. Several recent reports describe that, despite the neurodegenerative nature of Wolfram syndrome, some patients can achieve substantial hearing improvement after cochlear implantation. For instance, Lim et al. (5) documented that individuals with profound hearing loss due to WFS1 variants may still achieve functional speech understanding when pre-operative neural integrity is maintained. Similarly, another reports (6, 7) showed positive auditory outcomes following implantation, noting that postoperative improvements depend on residual cochlear nerve function and central auditory pathway integrity. These observations correspond with our patient’s postoperative functional gains, supporting the notion that cochlear implantation should not be dismissed only on the basis of the fundamental neurodegenerative disorder. Comparative analysis with other published cases reveals additional fine distinctions. Some authors have reported atypical retinal findings, including vitelliform-like deposits and macular changes (10, 11) suggesting that visual involvement in WS1 continues above isolated optic atrophy. understanding of these wide retinal patterns may improve ophthalmologic surveillance strategies. Li et al. (12) described a familial or “Wolfram-like” presentation, demonstrating that genotype-phenotype relation is variable and highlighting the importance of detailed family studies and genetic counseling in each case, an approach applied in our evaluation through carrier testing and pedigree construction. Recent neuroimaging studies have also highlighted characteristic structural changes in WS1, including brainstem and cerebellar atrophy, hypothalamic involvement, and white-matter abnormalities (5, 13). These findings provide insight into the neurologic and behavioral symptoms frequently observed in these patients. Although wide neuroimaging was not performed at the time of this report, longitudinal neurologic monitoring remains necessary to assess potential progression of neurodegeneration. This case report is limited by its single patient design, restricting generalizability. Long-term follow-up is required to evaluate the stability of auditory improvement and the progression of visual and neurologic decline, which are known to follow a progressive course in Wolfram (DIDMOAD) syndrome (14). Although molecular diagnosis was confirmed, the genotype-phenotype relation of the WFS1 variant (c.547del) remains incompletely understood, highlighting the challenge of allelic heterogeneity in Wolfram syndrome (15). Broader family studies and longitudinal phenotyping may help understanding this relationship. Evaluating young patients with early-onset diabetes and visual or auditory abnormalities, as early genetic testing enables accurate diagnosis and informed counseling. Cochlear implantation may provide meaningful benefit even in progressive neurodegenerative conditions, and candidacy should be based on functional auditory potential rather than diagnosis alone. Importantly, awareness of the multisystem involvement of DIDMOAD is essential for surgeons, since unrecognized endocrine and airway abnormalities may significantly increase perioperative risk. Long-term follow-up and comprehensive genotype-phenotype data may further improve prognostication and multidisciplinary treatment planning. Conclusion This case highlights the critical importance of a multidisciplinary, surgically informed approach in managing Wolfram syndrome. It also demonstrates that cochlear implantation can significantly improve auditory function and quality of life, with the patient reporting meaningful improvements in communication, environmental sound awareness, and daily activities following the procedure. Abbreviations WS1 Wolfram Syndrome type 1 DIDMOAD Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness WFS1 Wolfram Syndrome 1 gene DM Diabetes Mellitus DI Diabetes Insipidus ENT Ear, Nose, and Throat CT Computed Tomography HbA1c Hemoglobin A1c ECAP Electrically-evoked Compound Action Potential NRT Neural Response Telemetry CI Cochlear Implant CIQOL-10 Cochlear Implant Quality of Life − 10 item questionnaire Declarations Ethics approval Ethics approval was not required for this case report in accordance with local and institutional guidelines. Written informed consent was obtained from the patient for participation and publication of this case report. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of data and material The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and confidentiality concerns but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Not Applicable. Author contributions MHT wrote the original draft; TZ collected the data. NAS, FS and SM were the patient’s doctors. All authors have read and approved the final version of the manuscript. Acknowledgements Not applicable. References Rigoli L, Lombardo F, Di Bella C. Wolfram syndrome and WFS1 gene. Clinical genetics. 2011;79(2):103-17. Caruso V, Raia A, Rigoli L. Wolfram Syndrome 1: A neuropsychiatric perspective on a rare disease. Genes. 2024;15(8):984. Frontino G, Delvecchio M, Prudente S, Sordi VD, Barboni P, Di Giamberardino A, et al. SID/SIEDP expert consensus on optimizing clinical strategies for early detection and management of wolfram syndrome. J Endocrinol Invest. 2025;48(3):507-25. Karzon R, Narayanan A, Chen L, Lieu JEC, Hershey T. Longitudinal hearing loss in Wolfram syndrome. Orphanet J Rare Dis. 2018;13(1):102. Lim HD, Lee SM, Yun YJ, Lee DH, Lee JH, Oh S-H, et al. WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome. BMC medical genomics. 2023;16(1):79. Li T, Yang C, Zou H. Two cases of Wolfram syndrome. [Zhonghua yan ke za Zhi] Chinese Journal of Ophthalmology. 2022;58(10):799-802. Marfatia H, Rattan A, Jain A. Cochlear implant in Wolfram syndrome: A case report. Cochlear Implants Int. 2024;25(6):487-91. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. The CARE guidelines: consensus-based clinical case reporting guideline development. Global advances in health and medicine. 2013;2(5):38-43. de Muijnck C, Brink JBT, Bergen AA, Boon CJF, van Genderen MM. Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum. Surv Ophthalmol. 2023;68(4):641-54. Rosanio FM, Di Candia F, Occhiati L, Fedi L, Malvone FP, Foschini DF, et al. Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum. Int J Environ Res Public Health. 2022;19(2). Munshani S, Ibrahim EY, Domenicano I, Ehrlich BE. The Impact of Mutations in Wolframin on Psychiatric Disorders. Front Pediatr. 2021;9:718132. Li S, Li X, Qu J. A Wolfram-like syndrome family: Case report. Eur J Ophthalmol. 2024;34(4):Np51-np7. Peer S, Bhardwaj NK, Wander A. Neuroimaging features in Wolfram syndrome type 1. Neurol Sci. 2024;45(6):2943-4. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346(8988):1458-63. Lee EM, Verma M, Palaniappan N, Pope EM, Lee S, Blacher L, et al. Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders. Frontiers in genetics. 2023;14:1198171. Additional Declarations The authors declare no competing interests. Supplementary Files Care3.docx Care Checklist Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9646524","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":636436009,"identity":"53d98129-9289-4d32-8c80-1b5ef1a5ccd0","order_by":0,"name":"Fatemeh Sarv","email":"","orcid":"","institution":"Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Sarv","suffix":""},{"id":636436010,"identity":"9998f5ee-b2ee-4da0-9c5e-73d0993af145","order_by":1,"name":"Nasrin Asgari Soran","email":"","orcid":"","institution":"Hazrat Rasool Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.","correspondingAuthor":false,"prefix":"","firstName":"Nasrin","middleName":"Asgari","lastName":"Soran","suffix":""},{"id":636436011,"identity":"cdaae473-e542-4e19-949f-ef81d32ab151","order_by":2,"name":"Saleh Mohebbi","email":"","orcid":"","institution":"Skull base research Center, school of medicine, Iran University of medical sciences, Tehran, Iran.","correspondingAuthor":false,"prefix":"","firstName":"Saleh","middleName":"","lastName":"Mohebbi","suffix":""},{"id":636436012,"identity":"f5acd6d4-a73b-455b-88b9-e450c34c82d9","order_by":3,"name":"Tahereh Zabihi","email":"","orcid":"","institution":"Rasoul Akram Medical Complex Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran.","correspondingAuthor":false,"prefix":"","firstName":"Tahereh","middleName":"","lastName":"Zabihi","suffix":""},{"id":636436013,"identity":"2ecd9b8a-d5a5-4b69-9adf-1a4f98abf347","order_by":4,"name":"Mohammad Hossein Teymoori","email":"data:image/png;base64,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","orcid":"","institution":"Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.","correspondingAuthor":true,"prefix":"","firstName":"Mohammad","middleName":"Hossein","lastName":"Teymoori","suffix":""}],"badges":[],"createdAt":"2026-05-07 20:24:39","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9646524/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9646524/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109019201,"identity":"ba92c761-f7b7-447f-8b2a-6a40d04312c9","added_by":"auto","created_at":"2026-05-11 18:29:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":271338,"visible":true,"origin":"","legend":"\u003cp\u003ePedigree of the family demonstrating segregation of the WFS1 c.547del variant. Half filled symbols (individuals I 1, I 2, and II 1) indicate heterozygous carriers of the WFS1 c.547del variant. The fully filled circle with an arrow (individual II 2) denotes the affected proband who is homozygous for the WFS1 c.547del variant.\u003c/p\u003e","description":"","filename":"1000040956.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9646524/v1/6a8608071f5b19a79d348798.jpg"},{"id":109249347,"identity":"54d3e19b-58bd-4b1a-8c33-45c479673282","added_by":"auto","created_at":"2026-05-14 08:48:57","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1110866,"visible":true,"origin":"","legend":"\u003cp\u003eElectrode impedance values were classified as follows: valid (approximately 5–10 kΩ), indicating adequate electrode–tissue contact; short (\u0026lt;1 kΩ), suggestive of electrical short circuiting; open (\u0026gt;20 kΩ), indicating circuit discontinuity; and invalid, referring to values outside the reliable operating range of the recording system. In our patient, all electrode impedance values were within the valid (5–10 kΩ) range, with no electrodes classified as short, open, or invalid.\u003c/p\u003e","description":"","filename":"1000040958.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9646524/v1/0ad5e94173b0544ebf225c3e.jpg"},{"id":109250126,"identity":"53a028a6-43c9-4a5b-adec-10a5c435b0a6","added_by":"auto","created_at":"2026-05-14 09:06:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1507271,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9646524/v1/065259cb-e149-49b9-b61f-551ebc4e7012.pdf"},{"id":109067817,"identity":"8c4bbeda-590f-4814-bde9-9d25fd2f9be4","added_by":"auto","created_at":"2026-05-12 10:01:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":36390,"visible":true,"origin":"","legend":"\u003cp\u003eCare Checklist\u003c/p\u003e","description":"","filename":"Care3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9646524/v1/066b880b71c5867f7f51ff60.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eSuccessful Cochlear Implantation in a Patient With Wolfram Syndrome Type 1: a case report\u003cbr\u003e\n\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal recessive neurodegenerative disorder most commonly caused by pathogenic variants in the \u003cem\u003eWFS1\u003c/em\u003e gene (1, 2). The condition typically presents in childhood with insulin-dependent diabetes mellitus and progressive optic atrophy, followed by multisystem neurologic and sensory deterioration during adolescence and early adulthood (3, 4). Although cochlear implantation outcomes in Wolfram syndrome are variable due to underlying neurodegeneration, selected patients may still achieve meaningful auditory benefit when cochlear nerve integrity is preserved (5\u0026ndash;7). Given the rarity of Wolfram syndrome and the limited literature on auditory therapy, especially in Middle Eastern populations, reporting individual cases remains clinically valuable. We present a young woman with genetically confirmed Wolfram syndrome who underwent successful cochlear implantation with significant improvement in auditory perception and communication. This case underscores the importance of early referral, multidisciplinary management, and the role of cochlear implantation in selected patients. This manuscript conforms to the CARE guidelines for the reporting of case reports (8).\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 23-year-old Iranian woman with genetically confirmed Wolfram syndrome type 1 (DIDMOAD) was referred to our endocrinology clinic for poorly controlled diabetes mellitus. She had been diagnosed with diabetes at the age of two and had gradually developed progressive visual disability as well as severe bilateral sensorineural hearing loss during adolescence. In addition to long-standing diabetes mellitus, the patient had a documented history of central diabetes insipidus (DI) and was receiving desmopressin therapy at the time of presentation, completing the classic DIDMOAD phenotype. At presentation, she reported fatigue, polyuria, and distal paresthesia involving the plantar surface of the feet, suggestive of diabetic neuropathy. She was advised to use hearing aids since previous two years, however recently they were useless.\u003c/p\u003e \u003cp\u003eOn admission, laboratory evaluation showed markedly elevated fasting blood glucose (312 mg/dL), HbA1c of 9.5%, and elevated two-hour postprandial glucose (234 mg/dL). Her insulin regimen was therefore adjusted by increasing the basal dose and recalculating pre-meal boluses based on carbohydrate intake. She received advise on glucose monitoring, diet, and foot care, and was scheduled for close endocrinology follow-up.\u003c/p\u003e \u003cp\u003eAlthough the family initially reported no other affected members, genetic testing showed that both parents were heterozygous carriers of the WFS1 c.547del pathogenic variant, while the proband was homozygous. This finding confirmed the autosomal recessive inheritance pattern, and a pedigree was created to show carrier status within the family (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eBecause of her disabling hearing loss and low hearing aids positive effect, the patient was evaluated for cochlear implantation in our ENT department. Pre-operative audiological assessment showed no functional residual hearing, Speech recognition was less than 50 percent\u003c/p\u003e \u003cp\u003ein both ears and no significant benefit from amplification. She was candidate to ipsilateral\u003c/p\u003e \u003cp\u003ecochleal implantation. Temporal bone Computed Tomography (CT) scan was normal. The ENT committee has choose Advanced Bionic HiRes Ultra 3D/ HiFocus SlimJ with Nida CI Q90 Processor to implant.\u003c/p\u003e \u003cp\u003eShe was admitted to stabilized general condition and blood sauger pre-operatively and underwent cochlear implantation. The procedure was performed through a standard transmastoid posterior tympanotomy approach. The round window was exposed, and the electrode was smoothly inserted without resistance. Intraoperative neural response and impedance testing showed appropriate function of all sixteen electrodes, and no surgical complications were encountered. Initial device activation occurred three weeks after surgery. Post-operative programming showed stable stimulation thresholds across the array. Electrically-evoked Compound Action Potential\u003c/p\u003e \u003cp\u003e(ECAP) response was present. Neural Response Telemetry (NRT) value correlate with patient\u003c/p\u003e \u003cp\u003ebehavioral map. Impedance testing at activation confirmed normal electrical function of all sixteen electrodes, with values remaining stable over subsequent follow-ups (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eAfter nine months, the patient was satisfied and experienced progressive improvement in auditory perception. Although exact audiometric thresholds varied across visits, she repeatedly achieved meaningful access to conversational-level speech. Qualitatively, she reported being able to detect everyday environmental sounds, recognize familiar voices, and communicate effectively in quiet settings, abilities that were absent prior to implantation. The Cochlear Implant Quality of Life questionnaire (CIQOL-10) was administered to further assess postoperative outcomes.\u003c/p\u003e \u003cp\u003eThe patient continues multidisciplinary follow-up. Endocrinology manages her diabetes and neuropathic symptoms, ophthalmology monitors progressive optic atrophy, and audiology provides ongoing device programming and auditory rehabilitation. Speech therapy sessions focus on improving speech perception and communication strategies.\u003c/p\u003e \u003cp\u003eGenetic counseling was provided to the patient and her family regarding the autosomal recessive inheritance pattern and future reproductive considerations. Despite the progressive neurodegenerative nature of Wolfram syndrome, cochlear implantation in this case restored functional hearing and substantially improved the patient\u0026rsquo;s communication abilities and overall quality of life.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case represents a classic phenotype of WS1, supported by molecular confirmation of a homozygous \u003cem\u003eWFS1\u003c/em\u003e frameshift variant. Identification of heterozygous carrier status in both parents and construction of a pedigree further reinforce the autosomal recessive inheritance pattern. Studies across the WS1 range highlight substantial phenotypic variability among individuals with \u003cem\u003eWFS1\u003c/em\u003e mutations, with ophthalmic, neurologic, and psychiatric manifestations differing significantly even among related carriers (9). These findings are consistent with our patient\u0026rsquo;s combination of progressive visual decline, severe auditory dysfunction, and long-standing metabolic disease.\u003c/p\u003e \u003cp\u003eFrom an audiologic and otologic perspective, the successful cochlear implantation in our patient is clinically meaningful. Several recent reports describe that, despite the neurodegenerative nature of Wolfram syndrome, some patients can achieve substantial hearing improvement after cochlear implantation. For instance, Lim et al. (5) documented that individuals with profound hearing loss due to \u003cem\u003eWFS1\u003c/em\u003e variants may still achieve functional speech understanding when pre-operative neural integrity is maintained. Similarly, another reports (6, 7) showed positive auditory outcomes following implantation, noting that postoperative improvements depend on residual cochlear nerve function and central auditory pathway integrity. These observations correspond with our patient\u0026rsquo;s postoperative functional gains, supporting the notion that cochlear implantation should not be dismissed only on the basis of the fundamental neurodegenerative disorder.\u003c/p\u003e \u003cp\u003eComparative analysis with other published cases reveals additional fine distinctions. Some authors have reported atypical retinal findings, including vitelliform-like deposits and macular changes (10, 11) suggesting that visual involvement in WS1 continues above isolated optic atrophy. understanding of these wide retinal patterns may improve ophthalmologic surveillance strategies. Li et al. (12) described a familial or \u0026ldquo;Wolfram-like\u0026rdquo; presentation, demonstrating that genotype-phenotype relation is variable and highlighting the importance of detailed family studies and genetic counseling in each case, an approach applied in our evaluation through carrier testing and pedigree construction. Recent neuroimaging studies have also highlighted characteristic structural changes in WS1, including brainstem and cerebellar atrophy, hypothalamic involvement, and white-matter abnormalities (5, 13). These findings provide insight into the neurologic and behavioral symptoms frequently observed in these patients. Although wide neuroimaging was not performed at the time of this report, longitudinal neurologic monitoring remains necessary to assess potential progression of neurodegeneration.\u003c/p\u003e \u003cp\u003eThis case report is limited by its single patient design, restricting generalizability. Long-term follow-up is required to evaluate the stability of auditory improvement and the progression of visual and neurologic decline, which are known to follow a progressive course in Wolfram (DIDMOAD) syndrome (14). Although molecular diagnosis was confirmed, the genotype-phenotype relation of the WFS1 variant (c.547del) remains incompletely understood, highlighting the challenge of allelic heterogeneity in Wolfram syndrome (15). Broader family studies and longitudinal phenotyping may help understanding this relationship.\u003c/p\u003e \u003cp\u003eEvaluating young patients with early-onset diabetes and visual or auditory abnormalities, as early genetic testing enables accurate diagnosis and informed counseling. Cochlear implantation may provide meaningful benefit even in progressive neurodegenerative conditions, and candidacy should be based on functional auditory potential rather than diagnosis alone. Importantly, awareness of the multisystem involvement of DIDMOAD is essential for surgeons, since unrecognized endocrine and airway abnormalities may significantly increase perioperative risk. Long-term follow-up and comprehensive genotype-phenotype data may further improve prognostication and multidisciplinary treatment planning.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the critical importance of a multidisciplinary, surgically informed approach in managing Wolfram syndrome. It also demonstrates that cochlear implantation can significantly improve auditory function and quality of life, with the patient reporting meaningful improvements in communication, environmental sound awareness, and daily activities following the procedure.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWS1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWolfram Syndrome type 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDIDMOAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWFS1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWolfram Syndrome 1 gene\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiabetes Mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiabetes Insipidus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eENT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEar, Nose, and Throat\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHbA1c\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemoglobin A1c\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectrically-evoked Compound Action Potential\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeural Response Telemetry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCochlear Implant\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCIQOL-10\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCochlear Implant Quality of Life\u0026thinsp;\u0026minus;\u0026thinsp;10 item questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was not required for this case report in accordance with local and institutional guidelines. Written informed consent was obtained from the patient for participation and publication of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and confidentiality concerns but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMHT wrote the original draft; TZ collected the data. NAS, FS and SM were the patient’s doctors. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRigoli L, Lombardo F, Di Bella C. Wolfram syndrome and WFS1 gene. Clinical genetics. 2011;79(2):103-17.\u003c/li\u003e\n\u003cli\u003eCaruso V, Raia A, Rigoli L. Wolfram Syndrome 1: A neuropsychiatric perspective on a rare disease. Genes. 2024;15(8):984.\u003c/li\u003e\n\u003cli\u003eFrontino G, Delvecchio M, Prudente S, Sordi VD, Barboni P, Di Giamberardino A, et al. SID/SIEDP expert consensus on optimizing clinical strategies for early detection and management of wolfram syndrome. J Endocrinol Invest. 2025;48(3):507-25.\u003c/li\u003e\n\u003cli\u003eKarzon R, Narayanan A, Chen L, Lieu JEC, Hershey T. Longitudinal hearing loss in Wolfram syndrome. Orphanet J Rare Dis. 2018;13(1):102.\u003c/li\u003e\n\u003cli\u003eLim HD, Lee SM, Yun YJ, Lee DH, Lee JH, Oh S-H, et al. WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome. BMC medical genomics. 2023;16(1):79.\u003c/li\u003e\n\u003cli\u003eLi T, Yang C, Zou H. Two cases of Wolfram syndrome. [Zhonghua yan ke za Zhi] Chinese Journal of Ophthalmology. 2022;58(10):799-802.\u003c/li\u003e\n\u003cli\u003eMarfatia H, Rattan A, Jain A. Cochlear implant in Wolfram syndrome: A case report. Cochlear Implants Int. 2024;25(6):487-91.\u003c/li\u003e\n\u003cli\u003eGagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. The CARE guidelines: consensus-based clinical case reporting guideline development. Global advances in health and medicine. 2013;2(5):38-43.\u003c/li\u003e\n\u003cli\u003ede Muijnck C, Brink JBT, Bergen AA, Boon CJF, van Genderen MM. Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum. Surv Ophthalmol. 2023;68(4):641-54.\u003c/li\u003e\n\u003cli\u003eRosanio FM, Di Candia F, Occhiati L, Fedi L, Malvone FP, Foschini DF, et al. Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum. Int J Environ Res Public Health. 2022;19(2).\u003c/li\u003e\n\u003cli\u003eMunshani S, Ibrahim EY, Domenicano I, Ehrlich BE. The Impact of Mutations in Wolframin on Psychiatric Disorders. Front Pediatr. 2021;9:718132.\u003c/li\u003e\n\u003cli\u003eLi S, Li X, Qu J. A Wolfram-like syndrome family: Case report. Eur J Ophthalmol. 2024;34(4):Np51-np7.\u003c/li\u003e\n\u003cli\u003ePeer S, Bhardwaj NK, Wander A. Neuroimaging features in Wolfram syndrome type 1. Neurol Sci. 2024;45(6):2943-4.\u003c/li\u003e\n\u003cli\u003eBarrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346(8988):1458-63.\u003c/li\u003e\n\u003cli\u003eLee EM, Verma M, Palaniappan N, Pope EM, Lee S, Blacher L, et al. Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders. Frontiers in genetics. 2023;14:1198171.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Iran University of Medical Sciences","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Wolfram syndrome, DIDMOAD, Cochlear implantation, Sensorineural hearing loss, Case report","lastPublishedDoi":"10.21203/rs.3.rs-9646524/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9646524/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003cbr\u003e\nWolfram syndrome type 1 (DIDMOAD) is a rare autosomal recessive neurodegenerative disorder characterized by early-onset diabetes mellitus, optic atrophy, and progressive sensorineural hearing loss. Management of profound deafness in these patients is challenging, and outcomes of cochlear implantation remain variable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report a 23-year-old Iranian woman with genetically confirmed Wolfram syndrome type 1 who presented with poorly controlled diabetes, progressive visual impairment, and profound bilateral hearing loss refractory to hearing aids. Genetic testing revealed a homozygous frameshift variant in \u003cem\u003eWFS1\u003c/em\u003e, with both parents identified as heterozygous carriers. The patient underwent cochlear implantation without complications and achieved meaningful functional hearing, with marked improvement in communication and daily auditory perception.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003cbr\u003e\nThis case demonstrates that cochlear implantation can provide substantial auditory benefit in selected patients with Wolfram syndrome and highlights the importance of early genetic diagnosis and multidisciplinary management.\u003c/p\u003e","manuscriptTitle":"Successful Cochlear Implantation in a Patient With Wolfram Syndrome Type 1: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 18:29:38","doi":"10.21203/rs.3.rs-9646524/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0faae47a-1639-4629-bcf5-42b251ac47df","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T18:29:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 18:29:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9646524","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9646524","identity":"rs-9646524","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}