Papillorenal syndrome historical perspective

Historical Perspective

Rieger (1977) reported a family in which the father showed bilateral optic disc anomalies and died of chronic nephritis; his son showed macular and retinal abnormalities but renal function was normal, whereas his daughter had normal eyes but suffered from renal failure. This is a variability not unexpected for an autosomal dominant syndrome

Karcher (1979) described a father and son with the 'morning glory' optic disc anomaly and renal disease. Weaver et al. (1988) reported 2 brothers with optic nerve colobomas associated with renal disease. There is uncertainty as to whether the 'morning glory' syndrome represents a colobomatous defect or an abnormality of regression of mesodermal structures of the embryonic optic disc (Kindler, 1970; Dempster et al., 1983). Under the designation papillorenal syndrome, Bron et al. (1989) described the same disorder. Parsa (1998) also concluded that this is a condition of dysplastic discs rather than coloboma and that papillorenal syndrome is a more appropriate designation.

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.

Sanyanusin et al. (1995) reported further on 2 brothers with 'typical renal-coloboma syndrome without associated vesicoureteric reflux' who were originally described by Weaver et al. (1988). The younger brother had presented with severe progressive renal failure leading to renal transplantation and had a bilateral visual field defect with optic nerve colobomas. The older brother presented with chronic mild renal failure, a visual field defect, and optic nerve colobomas. The 2 brothers were the only affected family members and both parents had normal ophthalmologic examinations.

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