{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:04:21Z","timestamp":1790240661256,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Warsaw Breakage Syndrome (WABS), also termed DDX11-related cohesinopathy, is an exceptionally rare autosomal recessive disorder caused by biallelic pathogenic variants in DDX11. Sensorineural hearing loss is a recurrent manifestation and has frequently been reported together with structural abnormalities of the cochlea or cochlear nerve. Published experience with cochlear implantation in WABS remains extremely limited. Case Presentation: A 2.5-year-old boy was referred because of absent spoken-language development and limited responses to environmental and speech sounds. Newborn hearing screening had not been performed. After treatment of bilateral middle-ear effusions, comprehensive audiological assessment showed absent transient-evoked otoacoustic emissions and cochlear microphonics, no reproducible auditory brainstem response waveforms at the maximum tested level of 90 dB nHL, and auditory steady-state response estimates in the severe-to-profound range bilaterally. Clinical examination revealed microcephaly, short stature, and global developmental delay, raising suspicion of an underlying syndromic disorder. High-resolution computed tomography demonstrated normal cochlear morphology, while magnetic resonance imaging showed bilaterally visualized cochlear nerves without aplasia or marked hypoplasia. Whole-exome sequencing identified a pathogenic frameshift variant in DDX11 in apparent homozygosity, supporting the molecular diagnosis of WABS. Simultaneous bilateral cochlear implantation was performed at 3 years of age without complications. Longitudinal auditory development, assessed with the LittlEARS Auditory Questionnaire, improved from 0\/35 at activation to 10\/35 at 8 months, 21\/35 at 20 months, and 33\/35 at 24 months of auditory age. At approximately 30 months of auditory age, structured language assessments demonstrated further receptive and expressive communication gains, although language development remained influenced by the underlying neurodevelopmental disorder. At 33 months of auditory age, functional auditory performance assessed with PEACH-GR was 90% in quiet, 80% in noise, and 85% overall, while Greek-standardized language testing demonstrated persistent language difficulties relative to chronological-age expectations. Conclusions: Severe-to-profound prelingual sensorineural hearing loss in WABS may occur despite normal cochlear morphology and bilaterally visualized cochlear nerves. In this patient, simultaneous bilateral cochlear implantation was technically uncomplicated. During subsequent bilateral device use, programming, rehabilitation, and maturation, quantitatively documented progressive auditory development and functional communication gains were observed. Comprehensive audiological, radiological, genetic and developmental assessment is essential for individualized implant candidacy and realistic family counseling.<\/jats:p>","DOI":"10.3390\/diagnostics16193092","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:06:37Z","timestamp":1790237197000},"page":"3092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous Bilateral Cochlear Implantation in a Child with Warsaw Breakage Syndrome and Normal Cochlear Morphology: A Case Report and Focused Literature Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2249-7068","authenticated-orcid":false,"given":"Pinelopi","family":"Samara","sequence":"first","affiliation":[{"name":"Children\u2019s Oncology Hospital \u201cMarianna V. Vardinoyannis-ELPIDA\u201d, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Athanasopoulos","sequence":"additional","affiliation":[{"name":"Department of Otology, Audiology, and Pediatric Neurotology, Pediatric Center of Athens, 151 25 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Markatos","sequence":"additional","affiliation":[{"name":"Department of Otology, Audiology, and Pediatric Neurotology, Pediatric Center of Athens, 151 25 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Koudoumnaki","sequence":"additional","affiliation":[{"name":"Department of Otology, Audiology, and Pediatric Neurotology, Pediatric Center of Athens, 151 25 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Athanasopoulos","sequence":"additional","affiliation":[{"name":"Department of Otology, Audiology, and Pediatric Neurotology, Pediatric Center of Athens, 151 25 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Wallace, S.E., and Amemiya, A. (2026, July 22). DDX11-Related Cohesinopathy, GeneReviews\u00ae, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK541972\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1074\/jbc.M111.276022","article-title":"Biochemical characterization of Warsaw breakage syndrome helicase","volume":"287","author":"Wu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/humu.22226","article-title":"Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome","volume":"34","author":"Bharti","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1007\/s00018-014-1569-4","article-title":"Molecular functions and cellular roles of the ChlR1 (DDX11) helicase defective in the rare cohesinopathy Warsaw breakage syndrome","volume":"71","author":"Bharti","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pisani, F.M., Napolitano, E., Napolitano, L.M.R., and Onesti, S. (2018). Molecular and cellular functions of the Warsaw Breakage Syndrome DNA helicase DDX11. Genes, 9.","DOI":"10.3390\/genes9110564"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1038\/s41467-020-18066-8","article-title":"Warsaw Breakage Syndrome-associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion","volume":"11","author":"Faramarz","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ajhg.2010.01.008","article-title":"Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11\/ChlR1","volume":"86","author":"Chrzanowska","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejmg.2015.02.001","article-title":"Warsaw Breakage Syndrome\u2014A further report, emphasising cutaneous findings","volume":"58","author":"Bailey","year":"2015","journal-title":"Eur. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1002\/ajmg.a.38382","article-title":"Clinical report: Warsaw Breakage Syndrome with small radii and fibulae","volume":"173","author":"Eppley","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1002\/ajmg.a.40482","article-title":"Warsaw breakage syndrome: Further clinical and genetic delineation","volume":"176","author":"Alkhunaizi","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e639","DOI":"10.1002\/mgg3.639","article-title":"Two further patients with Warsaw breakage syndrome. Is a mild phenotype possible?","volume":"7","author":"Bottega","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1283","DOI":"10.1002\/mgg3.1283","article-title":"An audiological perspective on \u201cTwo further patients with Warsaw Breakage Syndrome. Is a mild phenotype possible?\u201d","volume":"8","author":"Brotto","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_13","first-page":"111","article-title":"Warsaw breakage syndrome: An etiology for congenital microcephaly and sensorineural deafness","volume":"76","year":"2023","journal-title":"Rev. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1002\/ajmg.a.61284","article-title":"Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases","volume":"179","author":"Rabin","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.32641\/andespediatr.v96i1.5094","article-title":"Warsaw syndrome: A cohesinopathy as etiology of primary microcephaly","volume":"95","author":"Leal","year":"2024","journal-title":"Andes Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100725","DOI":"10.1016\/j.xocr.2026.100725","article-title":"Surgical planning for paediatric cochlear implantation in Warsaw Breakage Syndrome using a 3D-reconstructed model of the malformed cochlea with a review of the literature","volume":"38","author":"Molnar","year":"2026","journal-title":"Otolaryngol. Case Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s00431-019-03379-8","article-title":"The etiological evaluation of sensorineural hearing loss in children","volume":"178","author":"Engel","year":"2019","journal-title":"Eur. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1097\/MAO.0000000000003841","article-title":"Targeted next-generation sequencing in children with bilateral sensorineural hearing loss: Diagnostic yield and predictors of a genetic cause","volume":"44","author":"Boudewyns","year":"2023","journal-title":"Otol. Neurotol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/00003446-200412000-00009","article-title":"Artifactual responses when recording auditory steady-state responses","volume":"25","author":"Small","year":"2004","journal-title":"Ear Hear."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.ijporl.2009.09.036","article-title":"Validation of the LittlEARS Auditory Questionnaire in children with normal hearing","volume":"73","author":"Coninx","year":"2009","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Binos, P., Stavrinos, G., and Taxitari, L. (2025). Validation of the Greek Parents\u2019 Evaluation of Aural\/Oral Performance of Children (PEACH) Rating Scale v.4 for Greek and Greek\u2013Cypriot Children with Typical Hearing. Audiol. Res., 15.","DOI":"10.3390\/audiolres15010011"},{"key":"ref_23","unstructured":"Vogindroukas, I., Protopapas, A., and Stavrakaki, S. (2011). Action Picture Test: Test of Informational and Grammatical Adequacy, Glafki. [Greek ed.]."},{"key":"ref_24","unstructured":"Vogindroukas, I., Protopapas, A., and Sideridis, G. (2009). Word Finding Vocabulary Test, Glafki. [Greek ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Yi, Z., Zhang, Y., Song, Z., Yang, C., Li, F., Liu, K., Li, J., and Xue, J. (2026). A pediatric patient with Warsaw breakage syndrome presenting with epilepsy: A case report and literature review. Front. Neurosci., 20.","DOI":"10.3389\/fnins.2026.1751535"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/pd.6684","article-title":"Prenatal diagnosis of Warsaw Breakage Syndrome: Fetal compound heterozygous variants in the DDX11 gene associated with growth restriction, cerebral, and extra-cerebral malformations","volume":"44","author":"Kratochwila","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_27","unstructured":"Joint Committee on Infant Hearing (2019). Year 2019 position statement: Principles and guidelines for early hearing detection and intervention programs. J. Early Hear. Detect. Interv., 4, 1\u201344."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.4274\/balkanmedj.2017.0367","article-title":"Classification and current management of inner ear malformations","volume":"34","author":"Bajin","year":"2017","journal-title":"Balk. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1080\/00016489.2023.2256790","article-title":"Determining optimal cochlear implant electrode array with OTOPLAN","volume":"143","author":"Yoshimura","year":"2023","journal-title":"Acta Otolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27308","DOI":"10.1038\/s41598-024-77991-6","article-title":"Estimation of outer-wall length in optimizing cochlear implantation in malformed inner ears","volume":"14","author":"Alshalan","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Samara, P., Athanasopoulos, M., Koudoumnaki, E., Markatos, N., and Athanasopoulos, I. (2026). Dual genetic diagnosis of Prader\u2013Willi syndrome and TMC1-related severe congenital hearing loss: Diagnostic challenges and cochlear implant outcomes. Diagnostics, 16.","DOI":"10.3390\/diagnostics16020300"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1097\/MAO.0b013e3182a004b3","article-title":"Systematic review of cochlear implantation in children with developmental disability","volume":"34","author":"Eze","year":"2013","journal-title":"Otol. Neurotol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1044\/2024_AJA-23-00272","article-title":"Prognostic value of electrophysiological and MRI findings for pediatric cochlear implant outcomes: A systematic review","volume":"33","author":"Jafari","year":"2024","journal-title":"Am. J. Audiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1097\/MAO.0b013e31826426d2","article-title":"Cochlear implant-evoked cortical activation in children with cochlear nerve deficiency","volume":"33","author":"He","year":"2012","journal-title":"Otol. Neurotol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/19\/3092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:24:54Z","timestamp":1790238294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/19\/3092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":34,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["diagnostics16193092"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16193092","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}