Table 1.

The diagnosis of X-linked Alport syndrome

Family history of Alport syndromeHigh (80%)HighA positive history will be obvious immediately, or the family will need to spend time asking distant family members. A family history may be absent with de novo disease or where families are small, there is no affected adult male, or disease is atypical.
Bilateral high-tone sensorineural hearing lossHighModerateAlso occurs with aging, middle ear infections, and industrial noise exposure. Hearing loss is also common in other inherited renal diseases and with renal failure and dialysis.
LenticonusLow to moderate (30%)Very highOnly occurs in Alport syndrome. May be misdiagnosed as cataract.
Central fleck retinopathyModerate (50%)Very highThe perimacular flecks occur only in Alport syndrome but may be overlooked or misdiagnosed.
Lamellated GBMHighVery highTypically generalized in affected adult males. Focal in boys and females but progresses with time.
α3α4α5(IV) collagen chains absent from GBMModerate (80% of males and 60% females)HighMay be focally absent in females.
α5(IV) collagen chain absent from skinModerate (80% of males and 60% females)HighMay be focally absent in females.
COL4A5 pathogenic variantHigh (>90%)HighMay be difficult to distinguish between pathogenic and nonpathogenic variants.