IllnessAlport syndrome, differential diagnosis

NGS +

[Sanger]

Alport syndrome is characterized by progressive renal disease, hearing loss and ocular abnormalities with hematuria and proteinuria leading to terminal renal failure. These patients also often develop sensorineural hearing loss as well as anterior lenticonus and retinal discoloration, although the latter rarely leads to blindness. Hypacusis, ocular abnormalities and progressive renal function impairment are more common in men than in women. In most cases, Alport syndrome is inherited X-linked (COL4A5 gene); in the remaining cases, autosomal dominant forms predominate over recessive forms (both inheritance patterns are observed for, both, the COL4A3 and COL4A4 genes). In addition, digenic inheritance of the three aformentioned COL4A genes has been reported. Virtually all cases of clinically confirmed Alport syndrome are clarified by sequencing of the three genes mentioned, with COL4A5 mutations contributing more than 80%. Inconspicuous genetic findings virtually exclude the suspected clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1207/

• Alias. Epstein syndrome
• Alias: Fechtner syndrome (MYH9)
• Allelic: Brain small vessel disease with/-out ocular anomalies (COL4A1)
• Allelic: Deafness, AD 17 (MYH9)
• Allelic: Hematuria, benign familial (COL4A3, COL4A4)
• Allelic: Hemorrhage, intracerebral, susceptibility to (COL4A1)
• Allelic: Microangiopathy + leukoencephalopathy, pontine, AD (COL4A1)
• Allelic: Retinal arteries, tortuosity of (COL4A1)
• Alport syndrome 1, XL (COL4A5)
• Alport syndrome 2, AR (COL4A3, COL4A4)
• Alport syndrome 3, AD (COL4A3)
• Angiopathy, hereditary, with nephropathy, aneurysms, muscle cramps (COL4A1)
• Macrothrombocytopenia, granulocyte inclusions with/-out nephritis, sensorineural hearing loss (MYH9)
• Nephropathy + deafness [+ocular anomalies] (COL4A5)