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Cochlear nerve deficiency, absence or hypoplasia, is commonly associated with cochlear canal stenosis or with CHARGE syndrome, a monogenic condition that affects inner ear development. SOX11 is a transcription factor essential for neuronal identity, highly correlated with the expression of <jats:italic>CHD7,<\/jats:italic> which regulates <jats:italic>SOX11<\/jats:italic>. We present two unrelated probands, each with novel de novo <jats:italic>SOX11<\/jats:italic> likely pathogenic variants and phenotypic manifestations of CSS including global developmental delay, growth deficiency, and hypoplastic nails. They have unilateral sensorineural hearing loss due to cochlear nerve deficiency confirmed on MRI. <jats:italic>SOX11<\/jats:italic> is implicated in sensory neuron survival and maturation. It is highly expressed in the developing inner ear. Homozygous ablation of <jats:italic>SOX11<\/jats:italic> in a mouse model resulted in a reduction in sensory neuron survival and decreased axonal growth. A heterozygous knockout mice model had hearing impairment with grossly normal inner ear structures like the two probands reported. We propose cochlear nerve deficiency as a new phenotypic feature of <jats:italic>SOX11\u2010<\/jats:italic>related CSS. Magnetic resonance imaging is useful in delineating the cochlear nerve deficiency and other CSS\u2010related brain malformations.<\/jats:p>","DOI":"10.1002\/ajmg.a.62851","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T08:54:16Z","timestamp":1654073656000},"page":"2460-2465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cochlear nerve deficiency in <scp><i>SOX11<\/i><\/scp>\u2010related <scp>Coffin\u2010Siris<\/scp> syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-3236","authenticated-orcid":false,"given":"Salam","family":"Alburaiky","sequence":"first","affiliation":[{"name":"Genetic Health Service New Zealand\u2014Northern Hub  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliet","family":"Taylor","sequence":"additional","affiliation":[{"name":"Genetic Health Service New Zealand\u2014Northern Hub  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"O'Grady","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Starship Children's Hospital  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Paediatric Radiology Starship Children's Hospital  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Paediatric Radiology Starship Children's Hospital  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleina M.","family":"England","sequence":"additional","affiliation":[{"name":"Center for Mendelian Genomics, Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Yap","sequence":"additional","affiliation":[{"name":"Genetic Health Service New Zealand\u2014Northern Hub  Auckland New Zealand"},{"name":"Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.11.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.403406"},{"key":"e_1_2_8_4_1","volume-title":"SVI recommendation for absence\/rarity (PM2)\u2014Version 1.0","author":"Clingen","year":"2020"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"First observation of secondary childhood glaucoma in coffin\u2010Siris syndrome: A case report and literature review","volume":"21","author":"Diel H.","year":"2021","journal-title":"BMC Ophthalmology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn162"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.05.002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172383099"},{"key":"e_1_2_8_9_1","first-page":"635","article-title":"Imaging findings of cochlear nerve deficiency","volume":"23","author":"Glastonbury C. 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