2017 Sec 1 Green Book

Hum Genet (2016) 135:441–450

Hearing loss

Presentation Evaluation Action

Detailed history and physical

Otherwise normal PE a

Additional findings on PE

Symmetric Asymmetric Unilateral

Common syndrome b

Uncommon syndrome b

Non-targeted syndrome c

Refer to Genetics

Order CGT

Order CGT

Do NOT order CGT

Consider CGT

41.0% 47.6% 27.8%

35.3%

25.3%

Appropriate referrals (genetics, ophthalmology, etc) and ancillary tests (TFTs, EKG, etc)

Follow-up

Acknowledgments  We are grateful to the patients and families included in this study. We thank all physicians and genetic counselors for allowing us to help in the care of their patients. This work was supported by T32 GM007337 to the University of Iowa MSTP and by NIDCD RO1s DC003544, DC002842 and DC012049 to RJHS. Fig. 4   Recommended diagnostic workflow of a patient with hear- ing loss showing the value of comprehensive genetic testing (CGT) with TGE and the expected diagnostic rate in percentage. A thorough physical and history is essential and determine the expected outcome of CGT. Patients with complex phenotypes may require referral to specialists. Additional phenotypic information on select syndromes is presented in Table S6. Questions regarding the appropriateness of testing can be sent to morl@uiowa.edu. PE physical exam, CGT comprehensive genetic testing, NSHL non-syndromic hearing loss, TFT thyroid function test. a Several forms of syndromic hearing loss may present as NSHL and are referred to as ‘NSHL mimics’. CGT includes the diagnosis of these NSHL mimics. b Common syndromes Conflict of interest  CMSH, AOB, AES, DLK, CJN, KLF, SSE, SBS, KTB, CAC, PTR, AEW, EABZ, DW, and HA disclose no con- flict of interest. RJHS directs the MORL, which offers TGE  +  MPS as a clinical diagnostic test for hearing loss. Open Access  This article is distributed under the terms of the Crea- tive Commons Attribution 4.0 International License ( http://creativecom- mons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Compliances with ethical standards

that can be detected by an otolaryngologist and are targeted by this CGT include Usher syndrome, Pendred syndrome and BOR syn- drome. For a complete list of syndromes included on the current CGT panel see Table S8. c Some individuals will present with extremely rare/private syndromes or phenotypes that reflect the co-occurrence of two (or rarely more) syndromes. CGT should be considered for the latter cohort of patients. CGT with the OtoSCOPE panel is not indi- cated in patients with neurological findings such as epilepsy, intel- lectual delay and autism, and in patients with complex multisystem syndromes that include hearing loss caused by genes NOT targeted for capture by OtoSCOPE

References

Bazazzadegan N et al (2012) The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss–a twelve year study. Int J Pediatr Otorhinolaryngol 76:1164–1174. doi: 10.1016/j.ijporl.2012.04.026 Blankenberg D et al. (2010) Galaxy: a web-based genome analy- sis tool for experimentalists. Curr Protoc Mol Biol 10:11–21. doi: 10.1002/0471142727.mb1910s89 (Chapter 19:Unit 19) Chang EH, Menezes M, Meyer NC, Cucci RA, Vervoort VS, Schwartz CE, Smith RJ (2004) Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum Mutat 23:582–589. doi: 10.1002/humu.20048 Chen A et al (1995) Phenotypic manifestations of branchio-oto- renal syndrome. Am J Med Genet 58:365–370. doi: 10.1002/ ajmg.1320580413 Dai P et al (2009) GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. J Transl Med 7:26. doi: 10.1186/1479-5876-7-26

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