Estimates show approximately 10% of children with hypoplastic kidneys are linked to the disease. Many different histological abnormalities have been noted, including:
decrease in nephron number associated with hypertrophy
focal segmental glomerulosclerosis
interstitial fibrosis and tubular atrophy
multicystic dysplastic kidneyUp to one-third of diagnosed patients develop end stage kidney disease, which may lead to complete kidney failure. Causes
Pax2 mutations
The majority of mutations occur in exons 2,3 and 4, which encode the paired domain and frame shift mutations that lead to a null allele. The missense mutations appear to disrupt hydrogen bonds, leading to decreased transactivation of Pax2, but do not seem to effect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind to its DNA consensus sequence. Mutations related to the disease have also been noted in exons 7,8, and 9, with milder phenotypes than the other mutations. Recent studies
Pax2 is expressed in the kidney, midbrain, hindbrain, cells in the spinal column, developing ear and developing eye. Homozygous negative Pax2 mutation is lethal, but heterozygote mutants showed many symptoms of papillorenal syndrome, including optic nerve dysplasia with abnormal vessels emerging from the periphery of the optic cup and small dysplasic kidneys. It is shown that Pax2 is under upstream control of Shh in both mice and zebrafish, which is expressed in the precordal plate. Other genes
Approximately half of patients with papillorenal syndrome do not have defects in the Pax2. This suggests that other genes play a role in the development of the syndrome, though few downstream effectors of Pax2 have been identified.
The least severe form of papillorenal disease shown in the eye is the exiting of blood vessels from the periphery that do not disturb the shape of the eye. Other eye malformations include scleral staphyloma, which is the bulging of the eye wall. There can also be retinal thinning and myopia. Additionally, there can be an optic nerve cyst, which is dilation of the optic nerve posterior to the globe; which most likely results from incomplete regression of the primordial optic stalk and the filling of this area with fluid. Retinal coloboma is also common, which is characterized by the absence of retinal tissue in the nasal ventral portion of the retina. However, this is an extremely rare finding. Molecular genetic testing
Sequence analysis shows that Pax2 is the only known gene associated with the disease. Mutations in Pax2 have been identified in half of renal coloboma syndrome victims. Treatment
Management of the disease should be focused on preventing end-stage kidney disease (ESKD) and/or vision loss. The treatment of hypertension may also preserve renal function. Renal replacement therapy is recommended, and vision experts may provide assistance to adapt to continued vision loss. Kidney transplant is also an option. Treatment plans seem to be limited, as there is a large focus on the prevention of papillorenal syndrome and its implications. People with congenital optic nerve abnormalities should seek ophthalmologists regularly and use protective lenses. If abnormalities are present, a follow up with a nephrologist should be achieved to monitor renal function and blood pressure.