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Errors in transcription factors such as those resulting from mutations in PAX2 cause widespread developmental anomalies.
Errors in transcription factors such as those resulting from mutations in PAX2 cause widespread developmental anomalies.

Papillorenal Syndrome

Clinical Characteristics

Ocular Features

Optic disc dysplasia is the ocular hallmark of this disease.  The nerve head often has the appearance of the ‘morning glory’ anomaly but some authors describe this as a coloboma or an optic pit.  Iris colobomas do not occur and only two patients have been reported with retinal colobomas.  There may be severe visual impairment due to the dysplastic optic nerves, but macular and retinal malformations may also contribute.  Other patients have near normal vision. The central retinal vessels are anomalous or even absent with the multiple smaller vessels exiting from the periphery of the disc.  The retina and fovea have been described as hypoplastic and have pigmentary changes. There is often a superonasal visual field defect.  Retrobulbar optic nerve cysts, high myopia, and posterior staphylomas have been noted in a few patients.  As in most autosomal dominant disorders, there is considerable clinical variability.

Systemic Features

Kidney dysfunction leading to chronic renal disease is the most common systemic abnormality in this condition.  It can occur at any age.  This often but not always is the result of pyelonephritis secondary to urogenital anomalies causing vesicoureteral reflux.  Other renal disease such as cystic renal hypoplasia may be present.  Other patients have only mild kidney malfunction with proteinuria and elevated serum creatinine.  A minority of patients has a mild high frequency hearing loss and rare individuals have CNS malformations.  Joint laxity and soft skin have also been described.

Genetics

This is an autosomal dominant disorder resulting from heterozygous mutations in the PAX2 gene (10q24.31). Nearly half of reported cases are sporadic secondary to new mutations.  Yet other well-studied families do not have mutations in the PAX2 gene suggesting genetic heterogeneity.

Optic nerve colobomas (120430) may also result from mutations in PAX6.

Treatment Options

Kidney failure may require renal transplantation.  Vesicoureteral reflex has been treated with ureteral reimplantation.  Low vision aids may be beneficial in some patients.  Renal hypertension requires treatment.

References

Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Birk Jensen U, Cochat P, Decramer S, Dixon J, Drouin R, Falk M, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morinière V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton D, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand D, Eccles M, Schimmenti LA, Heidet L. Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus specific database. Hum Mutat. 2011 Dec 29. [Epub ahead of print]

PubMed ID: 
22213154

Higashide T, Wada T, Sakurai M, Yokoyama H, Sugiyama K. Macular abnormalities and optic disk anomaly associated with a new PAX2 missense mutation. Am J Ophthalmol. 2005 Jan;139(1):203-5.

PubMed ID: 
15652857

Parsa CF, Silva ED, Sundin OH, Goldberg MF, De Jong MR, Sunness JS, Zeimer R, Hunter DG. Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity. Ophthalmology. 2001 Apr;108(4):738-49.

PubMed ID: 
11297491

Eccles MR, Schimmenti LA. Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. Clin Genet. 1999 Jul;56(1):1-9. Review.

PubMed ID: 
10466411