Usher syndrome exists in three types with type 1 patients being the most severely affected, whilst type 2 and 3 represent moderate and mild entities of this syndrome, respectively. Affected heterozygotic children are usually asymptomatic while homozygotes displaying a wide array of features present most often since birth.
A moderate to profound sensorineural hearing loss in both ears is seen at birth in homozygotic type 1 and type 2 patients. They may also concurrently develop speech deficits. Type 3 patients present with normal hearing at birth.
The sensorineural deafness is often diagnosed in isolation until the features of retinitis pigmentosa become apparent. Retinitis pigmentosa is initially marked by symmetrical and bilateral degeneration of the peripheral regions of the retina and later spreading to the more central regions . Frequently, the initial symptoms noticed by the individual or his/her parents or teachers include night blindness and tunnel vision, with the constriction of visual fields continuing well into adulthood . These features occur much earlier in type 1 patients than in the other types. Complete blindness may develop in these individuals.
Another important feature exclusive only to type 1 Usher syndrome patients is vestibular areflexia due to which walking milestones are achieved at a later date than usual (18 months to 2 years). Other children may appear clumsy whilst walking with frequent injuries being reported in these patients.
The diagnosis of Usher syndrome is primarily clinical and should be suspected in individuals who present with the clinical features as listed above amidst otherwise normal physical examination. These include sensorineural deafness, vestibular areflexia, and retinitis pigmentosa. A thorough assessment to detect the presence and severity of these conditions needs to be made via appropriate audiological, vestibular, and ophthalmologic evaluation. In addition, the presence of a family history of autosomal recessive diseases raises the likelihood of the presence of Usher syndrome in these individuals.
When the clinical features are inconclusive, molecular genetic testing techniques may be employed to reach a proper diagnosis. These may include serial single gene testing, multi-gene panels, or other extensive genomic tests to look for pathogenic variants of the related genes.
Single gene testing may involve the testing of genes such as the MY07A, USH1C, and CDH23 genes for type 1 patients. Testing for the USH2A, ADGRV1, and WHRN (DFNB31) genes may be required for type 2 patients   . Multi-gene panels may also be utilized to look for biallelic pathologic variants of the associated genes   . Other molecular techniques assessing the deletions and/or duplications of the genes may also be employed.
If the diagnosis is still uncertain, more comprehensive genomic tests (exome and full genome sequencing) may be carried out which may reveal mutations and diseases not included in the differential diagnosis previously.