Alport Syndrome - Criteria For The Clinical Diagnosis

Criteria For The Clinical Diagnosis

Gregory et al., 1996, gave the following 10 criteria for the diagnosis of Alport syndrome (four of the 10 criteria must be met):

• Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a male relative linked through any numbers of females.
• Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM disease, polycystic kidney disease or IgA nephropathy.
• Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range. The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30 years.
• A mutation in COL4An (where n = 3, 4 or 5).
• Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement membranes, or both.
• Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.
• Ocular lesions including anterior lenticonus, posterior subcapsular cataract, posterior polymorphous dystrophy and retinal flecks.
• Gradual progression to ESRD in the index case of at least two family members.
• Macrothrombocytopenia or granulocytic inclusions, similar to the May-Hegglin anomaly.
• Diffuse leiomyomatosis of esophagus or female genitalia, or both.

The use of eye examinations for screening has been proposed.

A review of pathogenic mutations detected in X-linked Alport syndrome patients in 2011, recommended COL4A5 analysis in any patient meeting at least two clinical diagnostic criteria and that COL4A3 and COL4A4 analysis should be considered if a COL4A5 mutation is not detected and primarily if autosomal inheritance is suspected.

Clinical utility gene card for: Alport syndrome.