Etiological approach in patients with unidentified hearing loss Ann N. Deklerck a , Frederic R. Acke a , Sandra Janssens b , Els M.R. De Leenheer a, * a Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium b Department of Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium 1. Introduction Approximately 2–4 in 1000 children are born with sensorineu- ral hearing loss (HL), making it the most prevalent birth defect [1,2]. This high prevalence, together with the early-onset HL among school-aged children and young adults, causes a substantial direct disease burden. Overall, the consequences of hearing impairment are highly underestimated [1–4]. Problems are not only linguistic, but also interfere with professional, social and psychological well-being. In order to minimize these effects, timely detection and effective intervention is desirable [5–7]. Further- more, determination of the cause of HL enables counseling, customized intervention, and anticipation of possible associated comorbidities [2]. Unlike acquired HL, the relative proportions of the various causes of congenital HL are well established. More than 50% of congenital HL is hereditary [1,2,8,9] of which the majority (2/3) is non-syndromic. The pattern of inheritance is autosomal recessive (AR) in 75% of these hearing losses. More than 50% of the AR non- syndromic losses are due to a mutation in the GJB2 gene, encoding Connexin 26 (Cx26) [1,10,11]. Regarding syndromic HL, some authors cite Waardenburg syndrome as the most prevalent otogenetic syndrome [12,13], while others define Pendred syndrome (SLC26A4 gene defect) as the most frequent [1]. Besides a genetic origin, environmental factors account for the remaining International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx A R T I C L E I N F O Article history: Received 23 September 2014 Received in revised form 6 December 2014 Accepted 9 December 2014 Available online xxx Keywords: Deafness Diagnosis Etiology Genetics Hearing loss A B S T R A C T Objectives: Etiological diagnosis of hearing impairment is of great importance to ensure early and adequate management. Even after thorough history taking, clinical and audiometric evaluation, the cause of hearing loss remains unclear in a majority of patients. Further examinations can imply imaging, ophthalmologic investigations, laboratory tests, electrocardiography and genetic testing. Lately, the latter has taken an increasingly prominent place within this diagnostic work-up. However, clear guidelines about optimal implementation and sequence of these tests are required. Methods: Records of patients who visited the consultation for otogenetics at Ghent University Hospital (Belgium) during the period 2006–2012 were retrospectively reviewed. In order to optimize the etiological-diagnostic work-up of unidentified hearing loss, application patterns and results of various diagnostic tests, audiometric and etiological data of each patient were collected and analyzed. Results: Data of 191 patients were analyzed. In 81.2% of the patients, a cause of hearing loss could be determined or suspected. In total, 65.4% had a (presumably) genetic etiology, with connexin 26 (GJB2) mutations as the leading cause. Inquiry of risk factors, associated with congenital hearing loss, and pedigree analysis were found to have the highest diagnostic gain (61.3% and 41.8%). Connexin 26 gene mutations were only present in bilateral hearing impairment, whereas CT abnormalities were related to unilateral (P = 0.003), profound (P < 0.001) hearing loss. An enlarged vestibular aqueduct was present in 42.9% of all CT abnormalities. Ophthalmologic anomalies were detected in 35.7% of the studied patients. Conclusions: A sequential approach for the etiological diagnosis of unidentified hearing loss could determine or suggest a cause in more than 80% of patients. The approach may vary based on the presenting phenotype. ß 2014 Elsevier Ireland Ltd. All rights reserved. Abbreviations: AD, autosomal dominant; AR, autosomal recessive; BOR syndrome, branchio-oto-renal syndrome; CMV, cytomegalovirus; Cx26, connexin 26; ECG, electrocardiography; EVA, enlarged vestibular aqueduct; HL, hearing loss; MIDD, maternally inherited diabetes and deafness; MT, mitochondrial. * Corresponding author. Tel.: +0032 9 332 23 32; fax: +0032 9 332 49 93. E-mail address: Els.DeLeenheer@UGent.be (Els M.R. De Leenheer). G Model PEDOT-7397; No. of Pages 7 Please cite this article in press as: A.N. Deklerck, et al., Etiological approach in patients with unidentified hearing loss, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.12.012 Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology jo ur n al ho m ep ag e: ww w.els evier .c om /lo cat e/ijp o r l http://dx.doi.org/10.1016/j.ijporl.2014.12.012 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.