Papillorenal syndrome historical perspective

Historical Perspective

Papillorenal syndrome for which another term used most commonly is Renal Coloboma Syndrome(RCS) . This condition usually consisting of renal anomalies plus optic nerve dysplasia. It is transmitted to generations in an Autosomal dominant fashion.

First clearly described by Weaver al in 1988. In two brothers having ESRD with coloboma in the eyes.

In 1995, the association of dominant mutations in PAX2 gene with RCS was made. It was studied in two generation family having renal dysplasia, coloboma of optic nerve and also the presence of vesicoureteral reflux.There are different opinions regarding the name of this condition between the observers. According to PubMed search performed in November,2010 the RCS is more common with 131 citations identified when the people searched for the term 'Renal Coloboma syndrome' and only 18 citations have been identified when people used the search term as 'Papillorenal syndrome'. The difference in results and the observation is mainly due to the differences in the explanation or description phenotypic changes in the eye. For many ophthalmologists, the eye findings are mainly due to failure of optic fissure to close during eye development and should be called as coloboma. For others the eye menifestations should be regarded as Dysplsia which

There are differences of opinion regarding the name of this condition between observers. RCS is the more common appellation in PubMed with 131 citations identified using the search term ‘Renal Coloboma syndrome' and 18 citations identified using the search term ‘Papillorenal syndrome' (PubMed search was performed November 26, 2010). The difference in nomenclature derives from differences in opinion regarding the description of the eye phenotype. To many ophthalmologists, the eye findings fall under the phenotype called ‘coloboma',⁵ meaning a condition that results from failure of the optic fissure to close during eye development. To others, the optic nerve findings should be described using the more general term, ‘dysplasia'⁶ with the preference for ‘papillorenal' syndrome where the word ‘papilla' refers to the optic papilla. In animal models, specifically mouse and zebrafish, Pax2/pax2a is expressed in the optic fissure; homozygous mutations lead to optic fissure closure defects and heterozygous mutations lead to similar defects as observed in human patients

Papillorenal syndrome is a combination of renal and ocular anomlies. Eccles and Schimmenti, 1999; Negrisolo et al., 2011 summarized Less common findings associated with expression of PAX2 gene in numerous tissues with disease include hearing loss, CNS anomlies, joint problems, ligament laxity, soft skin.

. 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.