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' as compared to only 18 citations that 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 other's the eye manifestation's should be regarded as Dysplasia.

Papillorenal syndrome is a combination of renal and ocular anomalies. 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 anomalies, joint problems, ligament laxity, soft skin.

This disorder have shown a wide variety of familial variability with variable presentation in different family members. The patients under the category of CAKUT that is 'congenital anomalies of kidney and urinary tract' presents with renal features without remarkable ocular changes, same is the case with some patients having PAX2 mutations. In these patients the ocular manifestations may be hard to detect without the use of advanced screening techniques or it can be normal as explained by Negrisolo et al., 2011; latropoulos at al., 2012.

The ocular and renal anomalies results in wide range of manifestation's. They commonly results in decreased visual activity along with the retinal detachment, renal insufficiency, proteinuria, hypertension, that can rapidly go on to develop end-stage renal disease. Summarised 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.