Not all cases of TBMN can be linked to mutations in COL4A3 and COL4A4. Research to better understand the spectrum of mutations that cause TBMN is ongoing. Extrarenal manifestations in TBMN are uncommon because the mutations are milder than those seen in HN and cause less severe disruptions in type IV collagen networks.

PRESENTATION

Hereditary Nephritis. Early renal manifestations of HN include persistent microscopic hematuria, usually beginning in childhood and often accompanied by intermittent episodes of gross hematuria. On microscopic evaluation, the RBCs often appear dysmorphic or in cast form, reflecting their glomerular origin. In the second through fourth decades of life, proteinuria, hypertension, and progressive renal insufficiency emerge. Extrarenal manifestations include sensorineural hearing loss and ocular abnormalities. Among males with X-linked disease, sensorineural hearing loss affects up to 80%, depending on how carefully screening is performed, whereas ocular abnormalities (such as anterior lenticonus, which is nearly pathognomonic of HN) affect approximately 25%.