Papillorenal syndrome historical perspective

Historical Perspective

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. (1995) and Sanyanusin et al. (1995) described a father and 3 sons had optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The 35-year-old father was more mildly affected than the sons. He had bilateral optic nerve colobomas but no renal problems recognized during childhood. An evaluation prompted by the renal problems in his sons demonstrated hypertension, mild proteinuria, and an elevated serum creatinine, but normal renal ultrasound. Ophthalmologic examination showed severe bilateral myopia, scleral staphyloma, and bilateral colobomas. Mild sensorineural hearing loss of unknown cause was also present. The oldest affected son, aged 15 years, had chronic renal failure and severe visual impairment. He first presented at 18 months for investigation of short stature. He already had renal insufficiency and showed a nonfunctioning right kidney and bilateral grade IV vesicoureteral reflux. The last ureteral reimplantation was performed at age 2. Hearing was normal. The second affected son, aged 10 years, had severe visual impairment, optic nerve colobomas, and mild renal dysfunction. He had grade II vesicoureteral reflux and small hypoplastic kidneys with poor corticomedullary differentiation. The third affected son, aged 6 years, had progressive renal failure for which he underwent renal transplantation at the age of 5 years.

Amiel et al. (2000) described a family in which 3 affected sibs showed striking ocular phenotypic variability. One sib had bilateral renal hypoplasia and 'morning glory' syndrome, whereas the other 2 presented with isolated unilateral cystic renal hypoplasia with no obvious ocular manifestation. Careful ophthalmologic examination of the latter 2 sibs showed an optic disc anomaly in both: bilateral papillary dysplasia in one and bilateral optic nerve coloboma in the other.

Schimmenti et al. (1999) described a severely affected girl and a mildly affected mother and daughter, all of whom had PAX2 homoguanine tract (7G) missense mutations. The mother and daughter had optic nerve colobomas and the daughter had vesicoureteral reflux. The severely affected girl developed renal failure and had bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari-1 malformation. Thus, the phenotype associated with PAX2 mutations must be expanded to include brain malformations