{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:14:25Z","timestamp":1790280865315,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"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: Prader\u2013Willi syndrome (PWS) is an imprinting disorder not typically associated with severe congenital sensorineural hearing loss (SNHL). When profound SNHL is present in an infant with a known syndrome, an independent monogenic etiology should be considered. We report the first molecularly confirmed case of PWS co-occurring with biallelic pathogenic TMC1 variants causing congenital SNHL, outlining diagnostic challenges, cochlear implant (CI) outcomes, and implications for blended phenotypes. Case Presentation: A male infant with PWS due to a paternal 15q11.2\u2013q13 deletion failed newborn hearing screening. Diagnostic auditory brainstem response and auditory steady-state response confirmed bilateral severe-to-profound SNHL. Temporal bone CT\/MRI were normal. Comprehensive genetic testing identified compound heterozygous TMC1 variants consistent with autosomal recessive DFNB7\/11 hearing loss, plus two variants of uncertain significance in SERPINB6 and EPS8L2. Sequential bilateral cochlear implantation was performed (left ear at 14 months, right at 20 months), followed by auditory\u2013verbal therapy. Over four years, the child showed steady improvements in hearing and early-speech development. Conclusions: Early genomic evaluation is essential when clinical features appear atypical for a known syndrome. Identifying TMC1-related deafness enabled timely cochlear implantation and measurable gains. This case highlights that severe congenital SNHL in a syndromic infant may reflect a distinct monogenic disorder rather than phenotypic expansion of the primary syndrome, emphasizing the importance of recognizing blended phenotypes to guide precision-care strategies in rare disorders.<\/jats:p>","DOI":"10.3390\/diagnostics16020300","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:02Z","timestamp":1768816622000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dual Genetic Diagnosis of Prader\u2013Willi Syndrome and TMC1-Related Severe Congenital Hearing Loss: Diagnostic Challenges and Cochlear Implant Outcomes"],"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":"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":"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":"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":[[2026,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/1573396315666190716120925","article-title":"Prader\u2013Willi syndrome\u2014Clinical genetics, diagnosis and treatment approaches: An update","volume":"15","author":"Butler","year":"2019","journal-title":"Curr. 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