Diagnosing papillorenal syndrome: see the optic papilla

Abstract

Sirs, In their article “A clinico-genetic study of renal coloboma syndrome in children”, Cheong and colleagues accurately point out that a variety of PAX2 mutations, one of which they had discovered, can cause the described phenotype of associated ocular, renal and urinary tract anomalies seen in this autosomal dominant condition [1]. However, it should also be noted that many patients with the “renal coloboma” disorder do not have any identifiable mutations in the PAX2 gene [2, 3]. The syndrome is not defined by PAX2 genetic analysis, but by clinical findings. Cheong and co-workers employed the syndrome’s older “renal-coloboma” nomenclature [1] as opposed to the subsequent “papillorenal” designation. Precise language is important in this case, since confusion created by the term “coloboma” has led many investigators to consider incomplete closure of the embryonic optic fissure to be the cause of an optic nerve anomaly in cases where there is no supportive evidence for such an etiology [2]. Accordingly, the preferred OMIM appellation now is “papillorenal syndrome” [4] (OMIM #120330). It should be noted that the prefix “papillo” indicates the optic papilla as the site of the ocular abnormality and not that of the renal papillae. While the term “papillorenal” is also not fully descriptive of all the possible associated ocular or urinary tract anomalies (such as vesicoureteral reflux), it avoids the misnomer of “coloboma” and implications, thereof, of an unrelated pathophysiologic pathway. Cheong et al. correctly emphasize that there is considerable variability of ocular and urinary tract findings [1]. Among that variability, however, one constant feature exists and is clearly visible in the ocular fundus photographs they published: the lack of central retinal blood supply. Instead of central vessels within the optic papilla, the disc is variably excavated centrally; the cilioretinal vessels originate outside and at the periphery of the optic nerve supplying the retina (“vacant discs”). These disc vessels circumferentially make hairpin turns over the neuroretinal rim toward the retina. Though often asymptomatic, the absence of central retinal vasculature can be associated with retinal hypoplasia, causing visual field defects. In some instances, this can lead to secondary serous retinal detachments [5] which, if occurring early in development, can lead to relative microphthalmia. This bilaterally visible vascular anomaly of the optic papilla testifies to a systemically deficient process of angiogenesis (as opposed to vasculogenesis) [6]. Angiogenesis is most critical to the development of both eye and kidney, the most perfused tissues per gram weight of the human body. Angiogenic factors are involved in the budding of vascular endothelial cells from pre-existing vessels laid down by vasculogenesis [6]. These same factors also affect the budding of other tubular structures Pediatr Nephrol (2008) 23:1893–1894 DOI 10.1007/s00467-008-0870-6