Papillorenal syndrome historical perspective
Historical Perspective
Papillorenal syndrome is an autosomal dominant disorder characterized by both ocular and renal anomalies. Less common findings include high frequency hearing loss, central nervous system anomalies, soft skin, ligamentous laxity, and/or genital anomalies, consistent with the expression of PAX2 in these tissues during development (summary by Eccles and Schimmenti, 1999; Negrisolo et al., 2011). The disorder shows wide inter- and intrafamilial variability. The renal features are part of a spectrum of malformations termed congenital anomalies of the kidney and urinary tract (CAKUT; see, e.g., 610805), and some patients with PAX2 mutations may present with CAKUT without obvious ocular abnormalities. In these patients, ocular abnormalities may be subtle and difficult to detect without advanced screening methods or may be normal (summary by Negrisolo et al., 2011; Iatropoulos et al., 2012). Eye anomalies associated with PAX2 mutations consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, designated optic nerve 'coloboma' or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease (summary by Schimmenti, 2011). *****
Rieger in 1977 first reported a family in whom the male died because of chronic kidney disease and bilateral optic disc anomalies. His son on examination also showed eye changes involving macula and retina but on the kidney workup was normal but on the other hand, his daughter was having normal vision with no eye abnormalities suggested from renal failure. This is a variable expression not uncommon in Autosomal dominant syndrome.
Karcher in 1979 described a combined case of father and son from a family showing some eye anomalies and renal disease as well. The eye anomalies found in his son was named morning glory optic disc anomaly. There was a high uncertainty that whether morning glory includes colobomatous defects or its just the abnormal regression of mesodermal embryonic disc structures. Bron et al in 1989 described the same disorder under the term Papillorenal syndrome. In 1998 then Parsa concluded that this is most likely a condition of the dysplastic disc rather than being called coloboma, so the paillorenal syndrome was the most appropriate term designated.
Schimmenti et al. & Sanyanusin et al. in 1995 four individuals ( One father and 3 son) of having coloboma of optic nerve, kidney anomalies and also the presence of vesicoureteral reflux. The father on workup was found to be having normal with respect to the renal function. Although Eye examination showed the presence of myopia an coloboma in eyes bilaterally. But all 3 son was having kidneys and eyes affected to variable extent.
Amiel et al. in 2000 described a family of 3 members with striking ocular phenotypic variability. One of them was having renal hypoplasia along with eye manifestation while other 2 were having renal anomalies ( Unilateral cystic renal hypoplasia) with optic disc anomalies bilaterally.