2017 Sec 1 Green Book

Hum Genet (2016) 135:441–450

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.

Compliances with ethical standards

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.

References

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Hearing loss

Detailed history and physical

Symmetric Asymmetric Unilateral

Additional findings on PE

Otherwise normal PE

Refer to

Genetics

Appropriate referrals (genetics,

ophthalmology, etc) and ancillary

tests (TFTs, EKG, etc)

Non-targeted

syndrome

Common

syndrome

Uncommon

syndrome

25.3%

Presentation

Evaluation

Action

Consider

CGT

41.0%

47.6% 27.8%

Order

CGT

Do NOT

order

CGT

35.3%

Order

CGT

Follow-up

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

physical exam,

CGT

comprehensive genetic testing,

NSHL

non-syndromic hearing loss,

TFT

thyroid function test.

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.

Common syndromes

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.

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

150