Differential Diagnosis
Often, a family with more than one affected sib is thought to have nonsyndromic hearing loss (NSHL) (see Hereditary Hearing Loss and Deafness Overview) until the oldest is diagnosed with retinitis pigmentosa (RP). Subsequent visual evaluation often reveals the presymptomatic early stages of RP in younger affected sibs. Pathogenic variants associated with NSHL and RP can be inherited independently by a single individual whose symptoms mimic those of Usher syndrome . Larger families lessen the statistical probability of this occurrence because at least one sib is likely to inherit one pathogenic variant without the other. NSHL and RP are both relatively common, with frequencies of 1:1,000 and 1:4,000, respectively, and are characterized by extreme genetic heterogeneity (to date, 110 genes have been associated with NSHL and 80 genes have been associated with RP). Hereditary disorders characterized by both sensorineural hearing impairment and decreased visual acuity to consider in the differential diagnosis of Usher syndrome type II (USH2) are summarized in . Table 4. Genes of Interest in the Differential Diagnosis of Usher Syndrome Type II
Gene(s) | Disorder | MOI | Clinical Characteristics | Comment |
|---|
USH1 | AR | Congenital bilateral profound SNHL, vestibular areflexia, adolescent-onset RP | Children w/USH1 are usually do not walk until age 18 mos to 2 yrs due to vestibular involvement (those w/USH2 usually walk at age ~1 yr). CLRN1 | — |
HARS1 | USH3 (OMIM 276902, 614504) | AR | Postlingual progressive SNHL, late-onset RP, variable impairment of vestibular function | Some persons w/USH3 may have profound HL vestibular disturbance thus be clinically misdiagnosed w/USH1 or USH2.1 |
PEX1PEX6PEX12(13 genes)2 | Zellweger spectrum disorder (ZSD)3 | Intermediate/milder ZSD | AR(AD)4 | Mainly sensory deficits /or mild developmental delay; intellect may be normal. |
Source: GeneReviews — "Usher Syndrome Type II"
