Table 3 New classifification system for Alport syndrome and related disorders [12]
Inheritance | Affected gene(s) | Genetic state | Comments | Estimated risk of ESRD |
|---|---|---|---|---|
X-linked | COL4A5 | Hemizygous (male subjects) | Rate of progression to ESRD and timing of extrarenal manifestations strongly influenced by genotype | 100% |
Heterozygous (female subjects) | Risk factors for progression: gross hematuria, SNHL, proteinuria, GBM thickening and lamellation | Up to 25% | ||
Autosomal | COL4A3 or COL4A4 | Recessive (homozygous or compound heterozygous) | Rate of progression to ESRD and timing of extrarenal manifestations strongly influenced by genotype | 100% |
Dominant | Hematuria Includes patients previously diagnosed as TBMN/BFH Risk factors for rogression: proteinuria, FSGS, GBM thickening and lamellation, SNHL, or evidence of progression in patient or family, genetic modififiers | 20% or more among those with risk factors for progression, < 1% in absence of risk factors | ||
Digenic | COL4A3, COL4A4, and COL4A5 | COL4A3 and COL4A4 mutations in trans | Clinical fifindings and pedigree simulate autosomal recessive transmission | Up to 100% |
COL4A3 and COL4A4 mutations in cis | Clinical fifindings and pedigree simulate autosomal dominant transmission | Up to 20% | ||
Mutations in COL4A5 and in COL4A3 or COL4A4 | Inheritance pattern does not simulate any Mendelian transmission | Up to 100% (affected male subjects) |