Papillorenal syndrome physical examination

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Overview

In most of the patients, the symptoms will differ depending upon a case by case basis. People with a similar disease might have a variable presentation and may not have all the mentioned symptoms. This valuable information is usually collected from the database of Human phenotype Ontology (HPO). The HPO usually collects the symptoms is usually described or mentioned in the various publications and medical resources. The most common manifestations are Enlargement of the optic disc with blood vessels seen coming out from the periphery. Retinal vessels observed in patients with Renal-coloboma syndrome are more in number and tortuosity as compared to see in normal individuals. Less commonly seen anomalies are Scleral staphyloma, Optic nerve cyst, Microphthalmia, Reduced corneal diameters, Foveal hypoplasia, and macular anomalies. The most common renal abnormalities are Renal hypoplasia/ hypo dysplasia kidneys that have a malformed function with a small number of functional glomeruli and can develop ESRD at any point in the disease. Somewhere around 10% of the patients with these kidneys found to have PAX2 gene mutation. Oligomeganephronia Condition seen in some of the patients with Renal-coloboma syndrome and this usually refers to the marked reduction in the number of functionally intact nephrons Compensatory glomerular hypertrophy seen. Glomerulosclerosis and meningeal fibrous deposits are the most common findings seen on histopathology. Multicystic dysplastic kidneys- These are commonly seen in around 10% of the patients reported with RCS. ESRD- End-stage renal disease can happen anytime during the course of the disease.

Approx. 80- 98% of the Patients have these Symptoms
Medical Terms Other Names
Optic Nerve Dysplasia
Renal Insufficiency Renal failure


Physical examination

Renal-coloboma syndrome- Eyes and renal manifestations observed clinically. Right (A) and Left (B) wide and deeply excavated optic disc shown in the image suggestive of optic disc dysplasia, also called a variant of "Morning glory". Right (C) and Left (D) eye showing bilateral optic disc dysplasia and Macular degeneration of the left eye, Surrounded by numerous arrows shown. (E) Glomerulus showing mesangial cell proliferation on hematoxylin and eosin stain

Renal-coloboma syndrome mainly involves eyes and kidneys.

The organ-specific abnormalities commonly corresponds to tissue specific PAX2 gene[1][2] expression during the embryonic period. The commonly affected tissues are inner ear, brain (CNS), spinal cord and less commonly urogenital ridge[3][4][5]


Ocular Abnormalities

The most common associated eye abnormality is the dysplasia of the optic nerve.

The other common involved eye findings are-

The visual acuity for patients with Renal-coloboma syndrome ranges from normal to marked impairment in vision to near blindnes. 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 include varying degrees of myopia[8][9], calcified degeneration of cornea, retinal detachment, lens abnormalities/luxation[10] and/or progressive vision loss.

Renal Abnormalities

Renal malformations are commonly seen in all the patents with RCS and that too even before the appearance of eye anomalies[9][11].

The common Renal abnormalities found in RCS patients with PAX2 gene expression are

1. Renal hypoplasia/ hypo dysplasia[12]

  • kidneys that have a malformed function with a small number of functional glomeruli and can develop ESRD at any point in the disease.
  • Somewhere around 10% of the patients with these kidneys found to have PAX2 gene mutation[13][14]

2. Oligomeganephronia[15]

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

3. Multicystic dysplastic kidneys[16] - These are commonly seen in around 10% of the patients reported with Renal-coloboma syndrome.

4. Horseshoe kidney[17]

5. ESRD- End-stage renal disease can happen anytime during the course of the disease.

  • It can be present in the prenatal period[8][18] with a severe presentation of Hypoplastic, aplastic kidneys, or in some cases as oligomenorrhea that ultimately in some cases leads to the loss of the fetus.
  • ESRD can be seen in the prenatal period or in adults in the late seventh decade.

6. CAKUT- congenital abnormalities of kidney and urinary tract

  • Ureteropelvic junction obstruction
  • Medullary sponge kidneys
  • Renal malformations
  • Horse shoe kidneys
  • Duplication of Pyeloureteral region

7. Focal segmental glomerulosclerosis- PAX2 mutation variant has been reported in cases of autosomal dominant FSGS.

8. Other findings- Hypertension, Proteinuria, Vesicoureteral reflux.

Auditory findings

Other Less common clinical associations

The other less common findings seen in patients with RCS are Ligamentous laxity. So far only one patient is identified with Chiari 1 malformation with PAX2 mutation.


Symptoms based on physical examination and their predominance on patients with RCS


Approx. 30- 80% of the Patients have these Symptoms
Medical Terms Other Names
Multicystic kidney dysplasia
Myopia Near Sighted

Near Sightedness

Close Sightedness

Renal Hypoplsia
 Small Kidneys

Underdeveloped Kidneys

Renal dysplasia
Stage 5 Chronic Kidney Disease
Visual Impairment Impairment in vision

Loss of eye sight

Vesicoureteral Reflux


Approx. 5% - 25% of the Patients have these Symptoms
Medical Terms Other names
Cataract Clouding of the eye lens
Horse shoe kidneys
Lens Luxation Dislocated Lens
Hearing Impairment
Nephrolithiasis Kidney Stones
Nystagmus Rapid,

Involuntary, rhythmic eye movments.

Renal Malrotation
Retinal detachment
Strabismus Cross Eyes

Squint

Retinal Coloboma Hole in the back side of eye

References

  1. ↑ Cunliffe HE, McNoe LA, Ward TA, Devriendt K, Brunner HG, Eccles MR (October 1998). "The prevalence of [[PAX2]] [[mutations]] in patients with isolated colobomas or [[coloboma]] associated with [[urogenital]] [[anomalies]]". J. Med. Genet. 35 (10): 806–12. doi:10.1136/jmg.35.10.806. PMC 1051454. PMID 9783702. URL–wikilink conflict (help)
  2. ↑ 2.0 2.1 Schimmenti LA, Cunliffe HE, McNoe LA, Ward TA, French MC, Shim HH, Zhang YH, Proesmans W, Leys A, Byerly KA, Braddock SR, Masuno M, Imaizumi K, Devriendt K, Eccles MR (April 1997). "Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations". Am. J. Hum. Genet. 60 (4): 869–78. PMC 1712484. PMID 9106533.
  3. ↑ Terzić J, Muller C, Gajović S, Saraga-Babić M (July 1998). "Expression of PAX2 gene during human development". Int. J. Dev. Biol. 42 (5): 701–7. PMID 9712525.
  4. ↑ Tellier AL, Amiel J, Delezoide AL, Audollent S, Augé J, Esnault D, Encha-Razavi F, Munnich A, Lyonnet S, Vekemans M, Attié-Bitach T (July 2000). "Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome". Am. J. Med. Genet. 93 (2): 85–8. doi:10.1002/1096-8628(20000717)93:2<85::aid-ajmg1>3.0.co;2-b. PMID 10869107.
  5. ↑ Schimmenti LA, Manligas GS, Sieving PA (December 2003). "Optic nerve dysplasia and renal insufficiency in a family with a novel PAX2 mutation, Arg115X: further ophthalmologic delineation of the renal-coloboma syndrome". Ophthalmic Genet. 24 (4): 191–202. doi:10.1076/opge.24.4.191.17229. PMID 14566649.
  6. ↑ Higashide T, Wada T, Sakurai M, Yokoyama H, Sugiyama K (January 2005). "Macular abnormalities and optic disk anomaly associated with a new PAX2 missense mutation". Am. J. Ophthalmol. 139 (1): 203–5. doi:10.1016/j.ajo.2004.07.021. PMID 15652857.
  7. ↑ Samimi S, Antignac C, Combe C, Lacombe D, Renaud Rougier MB, Korobelnik JF (2008). "Bilateral macular detachment caused by bilateral optic nerve malformation in a papillorenal syndrome due to a new PAX2 mutation". Eur J Ophthalmol. 18 (4): 656–8. doi:10.1177/112067210801800430. PMID 18609495.
  8. ↑ 8.0 8.1 Schimmenti LA, Pierpont ME, Carpenter BL, Kashtan CE, Johnson MR, Dobyns WB (November 1995). "Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies". Am. J. Med. Genet. 59 (2): 204–8. doi:10.1002/ajmg.1320590217. PMID 8588587.
  9. ↑ 9.0 9.1 Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R (December 2001). "Renal-coloboma syndrome: report of a novel PAX2 gene mutation". Am. J. Ophthalmol. 132 (6): 910–4. doi:10.1016/s0002-9394(01)01231-4. PMID 11730657.
  10. ↑ Beby F, Roche O, Cochat P, Ranchin B, Kohler R, Bonifas C, Cordier MP, Attie-Bitach T, Burillon C, Denis P (July 2010). "New ocular phenotype associated with a mutation in the PAX2 gene". Eye (Lond). 24 (7): 1293–4. doi:10.1038/eye.2009.330. PMID 20075965.
  11. ↑ Amiel J, Audollent S, Joly D, Dureau P, Salomon R, Tellier AL, Augé J, Bouissou F, Antignac C, Gubler MC, Eccles MR, Munnich A, Vekemans M, Lyonnet S, Attié-Bitach T (November 2000). "PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism". Eur. J. Hum. Genet. 8 (11): 820–6. doi:10.1038/sj.ejhg.5200539. PMID 11093271.
  12. ↑ Weber S, Moriniere V, Knüppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiené A, Mir S, Montini G, Peco-Antic A, Wühl E, Zurowska AM, Mehls O, Antignac C, Schaefer F, Salomon R (October 2006). "Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study". J. Am. Soc. Nephrol. 17 (10): 2864–70. doi:10.1681/ASN.2006030277. PMID 16971658.
  13. ↑ Nishimoto K, Iijima K, Shirakawa T, Kitagawa K, Satomura K, Nakamura H, Yoshikawa N (August 2001). "PAX2 gene mutation in a family with isolated renal hypoplasia". J. Am. Soc. Nephrol. 12 (8): 1769–72. PMID 11461952.
  14. ↑ Negrisolo S, Benetti E, Centi S, Della Vella M, Ghirardo G, Zanon GF, Murer L, Artifoni L (December 2011). "PAX2 gene mutations in pediatric and young adult transplant recipients: kidney and urinary tract malformations without ocular anomalies". Clin. Genet. 80 (6): 581–5. doi:10.1111/j.1399-0004.2010.01588.x. PMID 21108633.
  15. ↑ Salomon R, Tellier AL, Attie-Bitach T, Amiel J, Vekemans M, Lyonnet S, Dureau P, Niaudet P, Gubler MC, Broyer M (February 2001). "PAX2 mutations in oligomeganephronia". Kidney Int. 59 (2): 457–62. doi:10.1046/j.1523-1755.2001.059002457.x. PMID 11168927.
  16. ↑ 16.0 16.1 Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M, Jüppner H, Alexander SI (September 2005). "Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2". J. Am. Soc. Nephrol. 16 (9): 2754–61. doi:10.1681/ASN.2005030239. PMID 16049068.
  17. ↑ Taranta A, Palma A, De Luca V, Romanzo A, Massella L, Emma F, Dello Strologo L (January 2007). "Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at Exon 8 is associated with a highly variable phenotype". Clin. Nephrol. 67 (1): 1–4. doi:10.5414/cnp67001. PMID 17269592.
  18. ↑ Ford B, Rupps R, Lirenman D, Van Allen MI, Farquharson D, Lyons C, Friedman JM (March 2001). "Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family". Am. J. Med. Genet. 99 (2): 137–41. doi:10.1002/1096-8628(2000)9999:999<00::aid-ajmg1143>3.0.co;2-f. PMID 11241473.
  19. ↑ Torres M, Gómez-Pardo E, Gruss P (November 1996). "Pax2 contributes to inner ear patterning and optic nerve trajectory". Development. 122 (11): 3381–91. PMID 8951055.

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