Presentation: Child with non-syndromic hearing loss

You see a three-year-old child with speech delay in clinic, accompanied by their parents. The child is otherwise fit and healthy, with normal gestation, birth and medical history. You perform a thorough physical and neurological examination, the findings of which are normal. You request an audiological assessment, and the results from the audiogram reveal bilateral sensorineural deafness.

• Genomic testing should be considered in cases of confirmed bilateral non-syndromic hearing loss with a possible monogenic cause (that is, there is no alternate explanation).
• In cases of confirmed unilateral non-syndromic hearing loss, genomic testing should be considered if there is also a family history of bilateral or unilateral hearing loss consistent with a monogenic cause (often suggested by audiograms).
• Some patients may initially be thought to have non-syndromic hearing loss but careful examination may reveal subtle signs of monogenic syndromes associated with hearing loss. Signs to look for include patches of white hair or skin and/or different colour eyes (suggestive of Waardenburg syndrome), facial asymmetry and/or coloboma (suggestive of CHARGE syndrome) preauricular pits or tags and/or branchial cysts/fistulae (suggestive of branchio-oto-renal syndrome). These patients are also eligible for genomic testing.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient or family. For non-syndromic hearing loss, this will typically be:
  • R67 Monogenic hearing loss: whole exome sequencing or large panel.
• This test does not include whole genome sequencing (WGS), therefore:
  • you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms; and
  • parental samples may be needed for interpretation of the child’s (proband’s) result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• These tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• Medline Plus: Non-syndromic hearing loss
• NHS England: National Genomic Test Directory

References:

• del Castillo I, Morín M, Domínguez-Ruiz M and others. ‘Genetic etiology of non-syndromic hearing loss in Europe’. Human Genetics 2022: volume 141, pages 683–696. DOI: 1007/s00439-021-02425-6
• Wang J, Xiang J, Chen L and others. ‘Molecular diagnosis of non-syndromic hearing loss patients using a stepwise approach’. Scientific Reports 2021: volume 11, article 4,036. DOI: 10.1038/s41598-021-83493-6

For patients

• Centers for Disease Control and Prevention: A parent’s guide to genetics and hearing loss (PDF, 28 pages)
• National Deaf Children’s Society: Does my child have a hearing loss?