Papillorenal syndrome physical examination: Difference between revisions

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==Overview==
==Overview==


In most of the patients the symptoms will differ depending upon case by case basis. People with similar disease might have a variable presentation and may not have all the mentioned symptoms. This valuable information is usually collected from the data base of Human phenotype ontology (HPO). the HPO usually collects the symptoms the are usually described or mentioned in the various publications and medical resources.  
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.   
 
 
{| class="wikitable"
{| class="wikitable"
|+Approx. 80- 98% of the Patients have these Symptoms
|+Approx. 80- 98% of the Patients have these Symptoms
!Medical Terms
!Medical Terms
!Other names
!Other Names
|-
|-
|Optic Nerve Dysplasia
|Optic Nerve Dysplasia
Line 14: Line 12:
|Renal Insufficiency
|Renal Insufficiency
|Renal failure
|Renal failure
|}
|}<br />


==Physical examination==
==Physical examination==
Line 20: Line 18:
__NOTOC__
__NOTOC__


[[File:Renal-coloboma syndrome.png|thumb|420x420px|'''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 left eye, Surrounded by numerous arrows shown. (E) Glomerulus showing mesangial cell proliferation on hematoxylin and eosin stain]]
[[File:Renal-coloboma syndrome.png|thumb|420x420px|'''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 expression during the embryonic period. The commonly  affected tissues are inner ear, brain (CNS), spinal cord and less commonly urogenital ridge.  
[[Renal-coloboma syndrome]] mainly involves [[eyes]] and [[kidneys]].  


===Ocular Abnormalities===
The organ-specific abnormalities commonly corresponds to [[tissue]] specific [[PAX2]] [[gene]]<ref name="pmid9783702">{{cite journal |vauthors=Cunliffe HE, McNoe LA, Ward TA, Devriendt K, Brunner HG, Eccles MR |title=The prevalence of [[PAX2]] [[mutations]] in patients with isolated colobomas or [[coloboma]] associated with [[urogenital]] [[anomalies]] |journal=J. Med. Genet. |volume=35 |issue=10 |pages=806–12 |date=October 1998 |pmid=9783702 |pmc=1051454 |doi=10.1136/jmg.35.10.806 |url=}}</ref><ref name="pmid9106533">{{cite journal |vauthors=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 |title=Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations |journal=Am. J. Hum. Genet. |volume=60 |issue=4 |pages=869–78 |date=April 1997 |pmid=9106533 |pmc=1712484 |doi= |url=}}</ref> expression during the embryonic period. The commonly  affected tissues are inner ear, brain (CNS), spinal cord and less commonly urogenital ridge<ref name="pmid9712525">{{cite journal |vauthors=Terzić J, Muller C, Gajović S, Saraga-Babić M |title=Expression of PAX2 gene during human development |journal=Int. J. Dev. Biol. |volume=42 |issue=5 |pages=701–7 |date=July 1998 |pmid=9712525 |doi= |url=}}</ref><ref name="pmid10869107">{{cite journal |vauthors=Tellier AL, Amiel J, Delezoide AL, Audollent S, Augé J, Esnault D, Encha-Razavi F, Munnich A, Lyonnet S, Vekemans M, Attié-Bitach T |title=Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome |journal=Am. J. Med. Genet. |volume=93 |issue=2 |pages=85–8 |date=July 2000 |pmid=10869107 |doi=10.1002/1096-8628(20000717)93:2<85::aid-ajmg1>3.0.co;2-b |url=}}</ref><ref name="pmid14566649">{{cite journal |vauthors=Schimmenti LA, Manligas GS, Sieving PA |title=Optic nerve dysplasia and renal insufficiency in a family with a novel PAX2 mutation, Arg115X: further ophthalmologic delineation of the renal-coloboma syndrome |journal=Ophthalmic Genet. |volume=24 |issue=4 |pages=191–202 |date=December 2003 |pmid=14566649 |doi=10.1076/opge.24.4.191.17229 |url=}}</ref>
The eye findings are-  


*Enlargement of optic disc with blood vessels seen coming out from the periphery.
<br />
*Retinal vessels observed in patients with RCS are more in number and tortuosity as compared to seen in the normal individuals.
 
*Other eye anomalies seen in patients with RCS are optic nerve dysplasia, morning glory abnormality.
===<u>Ocular Abnormalities</u>===
The most common associated [[eye]] abnormality is the <u>[[dysplasia]] of the [[optic nerve]]</u>.
 
The other common involved [[eye]] findings are-
 
*Enlargement of the [[optic]] disc with blood vessels seen coming out from the periphery.
*[[Retinal]] [[vessels]] in patients with [[Renal-coloboma syndrome|RCS]] are greater in number and [[tortuosity]] as compared to see in normal individuals.
*Other [[eye]] anomalies seen in patients with RCS are optic nerve dysplasia, morning glory abnormality.
*Less common seen anomalies are:
*Less common seen anomalies are:
**Scleral staphyloma,
**Scleral staphyloma,
**Optic nerve cyst,
**[[Optic nerve]] cyst,
**Microphthalmia,
**[[Microphthalmia]]
**Reduced corneal diameters
**Reduced [[corneal]] diameters
**Foveal hypoplasia and macular anomalies.
**[[Foveal hypoplasia]] and [[macular]] anomalies<ref name="pmid15652857">{{cite journal |vauthors=Higashide T, Wada T, Sakurai M, Yokoyama H, Sugiyama K |title=Macular abnormalities and optic disk anomaly associated with a new PAX2 missense mutation |journal=Am. J. Ophthalmol. |volume=139 |issue=1 |pages=203–5 |date=January 2005 |pmid=15652857 |doi=10.1016/j.ajo.2004.07.021 |url=}}</ref><ref name="pmid18609495">{{cite journal |vauthors=Samimi S, Antignac C, Combe C, Lacombe D, Renaud Rougier MB, Korobelnik JF |title=Bilateral macular detachment caused by bilateral optic nerve malformation in a papillorenal syndrome due to a new PAX2 mutation |journal=Eur J Ophthalmol |volume=18 |issue=4 |pages=656–8 |date=2008 |pmid=18609495 |doi=10.1177/112067210801800430 |url=}}</ref>


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.  
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]]<ref name="pmid8588587">{{cite journal |vauthors=Schimmenti LA, Pierpont ME, Carpenter BL, Kashtan CE, Johnson MR, Dobyns WB |title=Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies |journal=Am. J. Med. Genet. |volume=59 |issue=2 |pages=204–8 |date=November 1995 |pmid=8588587 |doi=10.1002/ajmg.1320590217 |url=}}</ref><ref name="pmid11730657">{{cite journal |vauthors=Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R |title=Renal-coloboma syndrome: report of a novel PAX2 gene mutation |journal=Am. J. Ophthalmol. |volume=132 |issue=6 |pages=910–4 |date=December 2001 |pmid=11730657 |doi=10.1016/s0002-9394(01)01231-4 |url=}}</ref>, calcified degeneration of [[cornea]], [[retinal]] detachment, [[lens]] abnormalities/luxation<ref name="pmid20075965">{{cite journal |vauthors=Beby F, Roche O, Cochat P, Ranchin B, Kohler R, Bonifas C, Cordier MP, Attie-Bitach T, Burillon C, Denis P |title=New ocular phenotype associated with a mutation in the PAX2 gene |journal=Eye (Lond) |volume=24 |issue=7 |pages=1293–4 |date=July 2010 |pmid=20075965 |doi=10.1038/eye.2009.330 |url=}}</ref> and/or progressive vision loss.


===Renal Abnormalities===
===<u>Renal Abnormalities</u>===
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
[[Renal]] malformations are commonly seen in all the patents with [[Renal-coloboma syndrome|RCS]] and that too even before the appearance of eye anomalies<ref name="pmid11730657">{{cite journal |vauthors=Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R |title=Renal-coloboma syndrome: report of a novel PAX2 gene mutation |journal=Am. J. Ophthalmol. |volume=132 |issue=6 |pages=910–4 |date=December 2001 |pmid=11730657 |doi=10.1016/s0002-9394(01)01231-4 |url=}}</ref><ref name="pmid11093271">{{cite journal |vauthors=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 |title=PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism |journal=Eur. J. Hum. Genet. |volume=8 |issue=11 |pages=820–6 |date=November 2000 |pmid=11093271 |doi=10.1038/sj.ejhg.5200539 |url=}}</ref>.


*Renal hypoplasia/ hypo dysplasia
The common Renal abnormalities found in [[Renal-coloboma syndrome|RCS]] patients with [[PAX2]] [[gene]] expression are  
**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
*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
**Compensatory glomerular hypertrophy seen.
**Glomerulosclerosis and meningeal fibrous deposits are most common findings seen on histopathology.


*Multicystic dysplastic kidneys - These are commonly seen in around 10% of the patients reported with RCS.
1. Renal hypoplasia/ hypo [[dysplasia]]<ref name="pmid16971658">{{cite journal |vauthors=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 |title=Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study |journal=J. Am. Soc. Nephrol. |volume=17 |issue=10 |pages=2864–70 |date=October 2006 |pmid=16971658 |doi=10.1681/ASN.2006030277 |url=}}</ref>


*Horse shoe kidney
*[[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<ref name="pmid11461952">{{cite journal |vauthors=Nishimoto K, Iijima K, Shirakawa T, Kitagawa K, Satomura K, Nakamura H, Yoshikawa N |title=PAX2 gene mutation in a family with isolated renal hypoplasia |journal=J. Am. Soc. Nephrol. |volume=12 |issue=8 |pages=1769–72 |date=August 2001 |pmid=11461952 |doi= |url=}}</ref><ref name="pmid21108633">{{cite journal |vauthors=Negrisolo S, Benetti E, Centi S, Della Vella M, Ghirardo G, Zanon GF, Murer L, Artifoni L |title=PAX2 gene mutations in pediatric and young adult transplant recipients: kidney and urinary tract malformations without ocular anomalies |journal=Clin. Genet. |volume=80 |issue=6 |pages=581–5 |date=December 2011 |pmid=21108633 |doi=10.1111/j.1399-0004.2010.01588.x |url=}}</ref>


*ESRD- End stage renal disease can happen anytime during the course of disease.
2. Oligomeganephronia<ref name="pmid11168927">{{cite journal |vauthors=Salomon R, Tellier AL, Attie-Bitach T, Amiel J, Vekemans M, Lyonnet S, Dureau P, Niaudet P, Gubler MC, Broyer M |title=PAX2 mutations in oligomeganephronia |journal=Kidney Int. |volume=59 |issue=2 |pages=457–62 |date=February 2001 |pmid=11168927 |doi=10.1046/j.1523-1755.2001.059002457.x |url=}}</ref>
**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.


*Other findings- Hypertension, Proteinuria, VUR.   
*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]]
**Vesicoureteral reflux can be present in association to patients with RCS but in most of the cases this resolves spontaneously.
*Compensatory [[glomerular]] hypertrophy seen.
**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 of condition.
*[[Glomerulosclerosis]] and mesangial fibrous deposits are the most common findings seen on histopathology.


===Auditory findings===
3. [[Multicystic]] [[dysplastic]] [[kidneys]]<ref name="pmid16049068">{{cite journal |vauthors=Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M, Jüppner H, Alexander SI |title=Multicystic dysplastic kidney and variable [[phenotype]] in a family with a novel deletion [[mutation]] of [[PAX2]] |journal=J. Am. Soc. Nephrol. |volume=16 |issue=9 |pages=2754–61 |date=September 2005 |pmid=16049068 |doi=10.1681/ASN.2005030239 |url=}}</ref> - These are commonly seen in around 10% of the patients reported with [[Renal-coloboma syndrome]].


*Hearing loss can be seen in only 10% of the patients affected with Renal-coloboma syndrome. 
4. [[Horseshoe kidney]]<ref name="pmid17269592">{{cite journal |vauthors=Taranta A, Palma A, De Luca V, Romanzo A, Massella L, Emma F, Dello Strologo L |title=Renal-coloboma syndrome: a single [[nucleotide]] deletion in the [[PAX2]] [[gene]] at Exon 8 is associated with a highly variable [[phenotype]] |journal=Clin. Nephrol. |volume=67 |issue=1 |pages=1–4 |date=January 2007 |pmid=17269592 |doi=10.5414/cnp67001 |url=}}</ref>
**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===
5. ESRD- [[End-stage renal disease]] can happen anytime during the course of the [[disease]].
 
*It can be present in the [[prenatal]] period<ref name="pmid8588587">{{cite journal |vauthors=Schimmenti LA, Pierpont ME, Carpenter BL, Kashtan CE, Johnson MR, Dobyns WB |title=Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies |journal=Am. J. Med. Genet. |volume=59 |issue=2 |pages=204–8 |date=November 1995 |pmid=8588587 |doi=10.1002/ajmg.1320590217 |url=}}</ref><ref name="pmid11241473">{{cite journal |vauthors=Ford B, Rupps R, Lirenman D, Van Allen MI, Farquharson D, Lyons C, Friedman JM |title=Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family |journal=Am. J. Med. Genet. |volume=99 |issue=2 |pages=137–41 |date=March 2001 |pmid=11241473 |doi=10.1002/1096-8628(2000)9999:999<00::aid-ajmg1143>3.0.co;2-f |url=}}</ref> 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]].
 
*[[Glomerulosclerosis]] and [[mesangial]] fibrosis are also seen in the evaluation of the patient with [[ultrasound]]<ref name="pmid9106533">{{cite journal |vauthors=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 |title=Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations |journal=Am. J. Hum. Genet. |volume=60 |issue=4 |pages=869–78 |date=April 1997 |pmid=9106533 |pmc=1712484 |doi= |url=}}</ref>
*[[Vesicoureteral reflux]] can be present in association to patients with [[Renal-coloboma syndrome]] but in most cases, this resolves spontaneously.
*Complicated UTI and fluid collection in the [[kidneys]] due to backflow( hydronephrosis)<ref name="pmid16049068">{{cite journal |vauthors=Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M, Jüppner H, Alexander SI |title=Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2 |journal=J. Am. Soc. Nephrol. |volume=16 |issue=9 |pages=2754–61 |date=September 2005 |pmid=16049068 |doi=10.1681/ASN.2005030239 |url=}}</ref> ultimately rwquires the [[surgery]] for the resolution of the condition.
 
===<u>Auditory findings</u>===
 
*[[Hearing loss]] can be seen in only 10% of the patients affected by [[Renal-coloboma syndrome]]. 
**As [[PAX2]] [[gene]] expression during the childhood regulates the cochlear development, a mutation in the [[PAX2]] gene can cause abnormalities with [[hearing]]
**The High frequency hearing loss seen in patients with [[Renal-coloboma syndrome]] appears to be significant factor rather than confusing it with age related [[hearing loss]]<ref name="pmid8951055">{{cite journal |vauthors=Torres M, Gómez-Pardo E, Gruss P |title=Pax2 contributes to inner ear patterning and optic nerve trajectory |journal=Development |volume=122 |issue=11 |pages=3381–91 |date=November 1996 |pmid=8951055 |doi= |url=}}</ref>
 
===<u>Other Less common clinical associations</u>===
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.
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.


<br />
==Symptoms based on physical examination and their predominance on patients with RCS==
<br />
{| class="wikitable"
|+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<br />
|Small Kidneys
Underdeveloped Kidneys
|-
|Renal dysplasia
|
|-
|Stage 5 Chronic Kidney Disease
|
|-
|Visual Impairment
|Impairment in vision
Loss of eye sight
|-
|Vesicoureteral Reflux
|
|}<br />
{| class="wikitable"
|+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.
<br />
|-
|Renal Malrotation
|
|-
|Retinal detachment
|
|-
|Strabismus
|Cross Eyes
Squint
|-
|Retinal Coloboma
|Hole in the back side of eye
|}


==References==
==References==

Latest revision as of 18:34, 12 September 2020

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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