Papillorenal syndrome historical perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

Overview

Papillorenal syndrome for which another term is Renal-Coloboma Syndrome (RCS). This condition usually consisting of renal anomalies plus optic nerve dysplasia. It is transmitted to future 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 a two-generation family having renal dysplasia, coloboma of the optic nerve, and also the presence of vesicoureteral reflux. There are different opinions regarding the name of this condition between the observers. 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.

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.

Weaver al in 1988 First clearly described papillorenal syndrome. 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 a two-generation family having renal dysplasia, coloboma of the optic nerve, and also the presence of vesicoureteral reflux. There are different opinions regarding the name of this condition between the observers.

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.

Schimmenti et al. & Sanyanusin et al. in 1995 four individuals ( One father and 3 sons) of having coloboma of the 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 a coloboma in the eyes bilaterally. But all 3 sons were having kidneys and eyes affected to a variable extent.

Parsa in 1998 concluded that this is most likely a condition of the dysplastic disc rather than being called coloboma, so the papillorenal syndrome was the most appropriate term designated.

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 the other 2 were having renal anomalies ( Unilateral cystic renal hypoplasia) with optic disc anomalies bilaterally.

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 of phenotypic changes in the eye. For many ophthalmologists, the eye findings are mainly due to the failure of the optic fissure to close during eye development and should be called coloboma. For others, eye manifestation should be regarded as Dysplasia.

Eccles and Schimmenti, 1999; Negrisolo et al., 2011 summarized Less common findings associated with expression of the PAX2 gene in numerous tissues with the disease include hearing loss, CNS anomalies, joint problems, ligament laxity, soft skin.

Schimmenti in 2011- Summarized The ocular and renal anomalies result in a wide range of manifestations. They commonly result in decreased visual activity along with retinal detachment, renal insufficiency, proteinuria, hypertension, which can rapidly go on to develop end-stage renal disease.

Negrisolo et al., 2011; latropoulos at al., 2012.- This disorder has shown a wide variety of familial variability with a variable presentation in different family members. The patients under the category of CAKUT that are 'congenital anomalies of the kidney and urinary tract' present with renal features without remarkable ocular changes, the 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.