Diagnosis & differential diagnosis

The diagnosis of Usher syndrome is established on clinical grounds by evaluations of hearing, balance (delayed onset of walking is quite suggestive of a balance defect) and vision. Electrophysiologic and subjective tests of hearing and retinal function, and a family history consistent with autosomal recessive inheritance are part of the diagnosis. Audiology tests may implement otoscopy, pure tone audiometry, assessment of speech perception, and, in some cases, auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). Examination of the vestibular function includes rotary chair, calorics, electro-nystagmography, and computerized posturography. Fundoscopy, visual acuity, visual field (Goldmann perimetry) and electroretinography (ERG) should detect the onset of visual impairment but should be adjusted to the age of the patient.

When available, molecular testing provides an accurate genetic diagnosis, which is useful for definition of the risks for other family members or future offspring. Clinical genetic testing may be available (depending on the country) for all identified USH genes. Many different mutations have been identified in the USH1 and USH2 genes. Many of these mutations are not recurrent ("private" mutations), and therefore, the best strategy to identify the mutations is currently to sequence all the coding exons and flanking splice sites. However, based on the finding that the R245X mutation in PCDH15 accounts for a large percentage of type I Usher syndrome in the Ashkenazi Jewish population, screening and early diagnosis should be offered to infants from this ethnic group who present with bilateral profound hearing loss and lack other causes of hearing impairment. Prenatal diagnosis and preimplantation genetic diagnosis for at-risk pregnancies require prior identification of the disease-causing mutations in the family. Mutation carrier testing for at-risk family members is possible if the two disease-causing mutations have been identified in the family.

Early clinical and molecular diagnosis of Usher syndrome and improved coordination between ophthalmological and otorhinolaryngological services is of crucial importance for early and adequate management of the patients with this disease.


Routine regular auditory and ophthalmologic evaluation is recommended to detect potentially treatable complications and changes that may require management modifications.

Differential diagnosis

Differential diagnoses include nonsyndromic hearing loss, deafness-dystonia-optic neuronopathy, viral infections, diabetic neuropathy, syndromes involving mitochondrial defects (Kearns-Sayre syndrome, Leber hereditary optic neuropathy) and other multisystemic genetic disorder such as Alström syndrome, Bardet-Biedl syndrome, CHARGE syndrome.