Ophthalmic and renal anomalies of this syndrome
are most often bilateral, but highly variable. The mutations in the PAX2
gene lead to colobomatous eye defects. Developmental abnormalities of the
optic fissure result in a group of defects including orbital cysts,
microphthalmia, optic disc dysplasia, and colobomas of the optic nerve
(sometimes referred to as “Morning Glory Disc Anomaly”) and retina at the
posterior pole of the globe. (Iris colobomas have not been observed in
patients with mutations in PAX2). Optic nerve colobomas involve the optic
nerve head or optic papilla, and also result in thinning of the surrounding
retinal epithelium, causing congenital blindness or loss of visual acuity,
although not all patients with optic nerve colobomas have visual defects.
Progressive deterioration of visual acuity over several decades has been
described. The kidneys often appear small. The degree of renal disease is
very variable, but the disease is usually progressive and often requires
dialysis and/or renal transplant (although the age at end-stage renal
disease is very variable). Patients with basically normal renal
function have also been described. Renal biopsies may demonstrate mesangial
fibrosis, glomerulosclerosis, glomerular hyalinization, hyperplastic
glomeruli, tubular atrophy, and an overall rarefaction of glomeruli.
Pathological examination of kidneys may find cortical thinning, hypoplastic
papillae, a decreased number of glomeruli in the cortex and collecting ducts
in the papilla, consistent with renal hypoplasia. Vesicoureteral reflux
(VUR) is common in these children; however, it is not known to which extent
VUR is responsible for the kidney changes described above. Some of these
patients may also suffer from high-frequency hearing loss, central nervous
system anomalies (seizure disorder, Arnold Chiari Syndrome Type I),
joint laxity, and genital anomalies (cryptorchidism).