Papillorenal syndrome physical examination

Physical examination

Clinical findings seen in RCS are seen mainly in eyes and kidneys. The organ specific abnormalities commonly corresponds to tissue specific PAX2 gene expression during the embryonic period. The commonly affected tissues are inner ear, brain (CNS), spinal cord and less commonly urogenital ridge.

Ocular Abnormalities

The eye findings are- Enlargement of optic disc with blood vessels seen coming out from the periphery. Also, the retinal vessels observed in patients with RCS are more in number and tortuosity as compared to seen in the normal individuals. The common termed anomalies and condition seen in patients with RCS are optic nerve dysplasia, morning glory abnormality. Less common seen anomalies are are scleral staphyloma, optic nerve cyst, Microphthalmia, reduced corneal diameters along with foveal hypoplasia and macular anomalies.

The visual acuity for patients with RCS ranges from normal to marked impairment in vision to near blindness. Nystagmus and strabismus noted in patients involved in different studies may or may not be considered as a part of this syndrome. Anisometric visual acuity also noted in patients with RCS varied from 20/20 in one eye to just mere light perception in the other eye. Other common findings seen in patients on examination includes varying degree of myopia, calcified degeneration of cornea, retinal detachment and/or progressive vision loss.

Renal Abnormalities

Renal malformations are commonly seen in all the patents with RCS and that too even before the apperarence of eye anomalies. Renal abnormalities found in RCS patients with PAX2 gene expression are-

1) Renal hypoplasia/ hypodysplasia- means kidneys that have malformed function with small number of functional glomeruli and can develop ESRD at any point of the disease. Somewhere around 10% of the patients with these kidneys found to have PAX2 gene mutation

2) Oligomeganephronia- Condition seen in some of the patients with Renal-coloboma syndrome and this usually refers to the marked reduction in number of functionally intact nephrons with some compensatory glomerular hypertrophy seen. Glomerulosclerosis and meningeal fibrous deposits are most common findings seen on histopathology.

3) Multicystic dysplastic kidneys - These are commonly seen in around 10% of the patients reported with RCS.

4) horse shoe kidney

5) ESRD- End stage renal disease can happen anytime during the course of disease. It can be present in the prenatal period with severe presentation of Hypoplastic, aplastic kidneys or in some cases as oligomennorhea that ultimately in some cases leads to the loss of fetus. ESRD can be seen in the prenatal period or in adults in the late seventh decade.

6) Other findings- Hypertension, Proteinuria, VUR. Vesicoureteral reflux can be present in association to patients with RCS but in most of the cases this resolves spontaneously and in severe cases it can be further complicated with infections of urinary tract and fluid collection in the kidneys due to back flow( hydronephrosis) ultimately requiring the surgery for the resolution ofc condition.

Auditory findings

Hearing loss can be seen in only 10% of the patients affected with Renal-coloboma syndrome. As PAX2 gene expression during the childhood regulates the cochlear development, a mutation in PAX2 gene can cause abnormalities with hearing. The High frequency hearing loss seen in patients with RCS appears to be significant factor rather than confusing it with age related hearing loss.

Other Less common clinical associations

The other less common findings seen in patients with RCS are Ligamentous laxityLigamentous laxity has been observed in a number of patients, but the underlying mechanism is uncertain.^{3, 14, 18} Chiari 1 malformation has been identified in a single patient with a PAX2 mutation.¹⁴ There are three reported individuals with developmental disability, although the majority of patients with PAX2 mutations have normal intellect.^{13, 19, 30}

Figure 1

Fundus photographs from three patients with renal coloboma syndrome (a–c) and a normal retina for comparison (d). (a) Left retina from a patient with RCS and PAX2 mutation c.76dup.¹⁴ The arrow denotes a deeply excavated optic disc. (b) Right retina from a patient with RCS and PAX2 mutation c.76delG.¹⁴ The arrow denotes a retinal defect, however, the defect is temporal rather than nasal. (c) Right retina from a patient with PAX2 mutation c.76dup.¹³ The optic disc is enlarged and excavated. In all three retinae from patients with renal coloboma syndrome the retinal vessels emerge from the edge of the disc rather than the center. (d) A normal retina for comparison. Note that the typical optic nerve is smaller, compact and the retinal vessels emerge from the center of the disc.

Figure 2

MRI of an optic nerve cyst in an affected patient with PAX2 mutation c.76dup denoted by the black arrow.¹⁴

Here are shown few pictures of fundus from patients with Renal-coloboma syndrome along with a picture of normal retina is placed for camparison

a- Left Retinal image of patient showing excavated optic disc in a patient with RCS having PAX2 mutation

b) Right retinal image showing temporal retinal defect

c) R retinal image showing optic disc enlargement in a patient having PAX2 mutation

The important point worth considering I'm all three images is the emergence of retinal vessels from the periphery of disc rather than from the center.

Image d) is kept fro comparison and is showing the normal retina with typical smaller optic nerve and retinal vessels emergence from the disc center as compared to patients with RCS with emergence from the edge or periphery.