MCID: PPL048
MIFTS: 53

Papillorenal Syndrome

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Neuronal diseases, Eye diseases, Fetal diseases

Aliases & Classifications for Papillorenal Syndrome

MalaCards integrated aliases for Papillorenal Syndrome:

Name: Papillorenal Syndrome 53 12 49 24 71 13 69
Renal Coloboma Syndrome 12 49 24 55 36 28 14
Coloboma of Optic Nerve with Renal Disease 53 12 49 24 55 71
Renal-Coloboma Syndrome 53 24 71 51
Congenital Anomalies of the Kidney and Urinary Tract with or Without Ocular Abnormalities 53 12 71
Optic Coloboma, Vesicoureteral Reflux, and Renal Anomalies 53 49 24
Renal-Coloboma Syndrome with Macular Abnormalities 53 12 71
Cakut with or Without Ocular Abnormalities 53 12 71
Optic Nerve Coloboma with Renal Disease 53 49 71
Paprs 53 71
Papillo-Renal Syndrome, Optic Nerve Coloboma with Renal Disease 12
Optic Coloboma, Vesicoureteral Reflux and Renal Anomalies 12
Optic Coloboma Vesicoureteral Reflux and Renal Anomalies 71
Optic Nerve Coloboma Renal Syndrome 24
Coloboma-Ureteral-Renal Syndrome 24
Papillo-Renal Syndrome 55
Oncr 24
Rcs 24

Characteristics:

Orphanet epidemiological data:

55
renal coloboma syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
onset in infancy
ocular abnormalities may be very mild
end-stage renal disease (ckd stage 5) requiring kidney transplantation is commonly reported


HPO:

31
papillorenal syndrome:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Papillorenal Syndrome

OMIM : 53 Papillorenal syndrome is an autosomal dominant disorder characterized by both ocular and renal anomalies. Less common findings include high frequency hearing loss, central nervous system anomalies, soft skin, ligamentous laxity, and/or genital anomalies, consistent with the expression of PAX2 in these tissues during development (summary by Eccles and Schimmenti, 1999; Negrisolo et al., 2011). The disorder shows wide inter- and intrafamilial variability. The renal features are part of a spectrum of malformations termed congenital anomalies of the kidney and urinary tract (CAKUT; see, e.g., 610805), and some patients with PAX2 mutations may present with CAKUT without obvious ocular abnormalities. In these patients, ocular abnormalities may be subtle and difficult to detect without advanced screening methods or may be normal (summary by Negrisolo et al., 2011; Iatropoulos et al., 2012). Eye anomalies associated with PAX2 mutations consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, designated optic nerve 'coloboma' or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease (summary by Schimmenti, 2011). (120330)

MalaCards based summary : Papillorenal Syndrome, also known as renal coloboma syndrome, is related to coloboma of macula and pax2-related disorder, and has symptoms including nystagmus, hearing impairment and visual impairment. An important gene associated with Papillorenal Syndrome is PAX2 (Paired Box 2), and among its related pathways/superpathways are Signaling pathways regulating pluripotency of stem cells and Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include kidney, eye and skin, and related phenotypes are cellular and embryo

UniProtKB/Swiss-Prot : 71 Papillorenal syndrome: An autosomal dominant disorder characterized by both ocular and renal anomalies, but may also include vesicoureteral reflux, high frequency hearing loss, central nervous system anomalies, and/or genital anomalies. Eye anomalies in this disorder consist of a wide and sometimes excavated dysplastic optic disk with the emergence of the retinal vessels from the periphery of the disk, designated optic nerve coloboma or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease.

NIH Rare Diseases : 49 Renal coloboma syndrome is a rare condition that affects kidney and eye development. It is characterized by small underdeveloped kidneys, malformation of the optic nerve, and sometimes a hole (coloboma) in the retina. People with renal coloboma syndrome may progress to end stage kidney disease and some people experience vision loss. Less common symptoms include vesicoureteral reflux, multiple kidney cysts, loose joints, and mild hearing loss. The syndrome has an autosomal dominant pattern of inheritance and can be caused by mutations in the PAX2 gene. In about half of cases, the underlying cause can not be determined. Last updated: 1/6/2012

Genetics Home Reference : 24 Renal coloboma syndrome (also known as papillorenal syndrome) is a condition that primarily affects kidney (renal) and eye development. People with this condition typically have kidneys that are small and underdeveloped (hypoplastic), which can lead to end-stage renal disease (ESRD). This serious disease occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. It has been estimated that approximately ten percent of children with hypoplastic kidneys may have renal coloboma syndrome. The kidney problems can affect one or both kidneys.

Disease Ontology : 12 An autosomal dominant disease characterized by optic nerve coloboma and renal disease that has material basis in heterozygous mutation in the PAX2 gene on chromosome 10q24.

Related Diseases for Papillorenal Syndrome

Graphical network of the top 20 diseases related to Papillorenal Syndrome:



Diseases related to Papillorenal Syndrome

Symptoms & Phenotypes for Papillorenal Syndrome

Symptoms via clinical synopsis from OMIM:

53
Skeletal:
joint laxity

Head And Neck Eyes:
microphthalmia
optic nerve coloboma
retinal coloboma
optic disc dysplasia
excavation of optic disc (pits)
more
Genitourinary Kidneys:
renal hypoplasia
renal cysts
congenital anomalies of the kidney and urinary tract (cakut)
end stage renal failure
multicystic dysplastic kidneys
more
Neurologic Central Nervous System:
normal intelligence
mental retardation (one patient)
seizure disorder
arnold chiari type i malformation

Laboratory Abnormalities:
proteinuria

Genitourinary Ureters:
vesicoureteral reflux
pyeloureteral duplication (rare)

Skin Nails Hair Skin:
hyperextensible skin
soft skin

Head And Neck Ears:
sensorineural hearing loss (rare)


Clinical features from OMIM:

120330

Human phenotypes related to Papillorenal Syndrome:

55 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000639
2 hearing impairment 55 31 occasional (7.5%) Occasional (29-5%) HP:0000365
3 visual impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000505
4 renal insufficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0000083
5 strabismus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000486
6 joint hyperflexibility 55 31 occasional (7.5%) Occasional (29-5%) HP:0005692
7 myopia 55 31 frequent (33%) Frequent (79-30%) HP:0000545
8 multicystic kidney dysplasia 55 31 frequent (33%) Frequent (79-30%) HP:0000003
9 vesicoureteral reflux 55 31 frequent (33%) Frequent (79-30%) HP:0000076
10 renal hypoplasia 55 31 frequent (33%) Frequent (79-30%) HP:0000089
11 optic nerve coloboma 55 31 occasional (7.5%) Occasional (29-5%) HP:0000588
12 renal dysplasia 55 31 frequent (33%) Frequent (79-30%) HP:0000110
13 retinal coloboma 55 31 occasional (7.5%) Occasional (29-5%) HP:0000480
14 optic nerve dysplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001093
15 edema 31 occasional (7.5%) HP:0000969
16 seizures 31 HP:0001250
17 joint laxity 31 HP:0001388
18 intellectual disability 31 HP:0001249
19 cataract 31 occasional (7.5%) HP:0000518
20 sensorineural hearing impairment 31 HP:0000407
21 proteinuria 31 HP:0000093
22 horseshoe kidney 31 occasional (7.5%) HP:0000085
23 microphthalmia 31 HP:0000568
24 retinal detachment 31 occasional (7.5%) HP:0000541
25 lens luxation 31 occasional (7.5%) HP:0012019
26 nephrolithiasis 31 occasional (7.5%) HP:0000787
27 macular degeneration 31 occasional (7.5%) HP:0000608
28 hyperextensible skin 31 HP:0000974
29 stage 5 chronic kidney disease 31 frequent (33%) HP:0003774
30 gliosis 31 HP:0002171
31 renal malrotation 31 occasional (7.5%) HP:0004712
32 arnold-chiari type i malformation 31 HP:0007099
33 chorioretinal atrophy 31 HP:0000533
34 soft skin 31 HP:0000977
35 macular hyperpigmentation 31 occasional (7.5%) HP:0011509
36 orbital cyst 31 HP:0001144
37 morning glory anomaly 31 HP:0025514

MGI Mouse Phenotypes related to Papillorenal Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.88 EYA1 OTX1 PAX2 PAX6 SALL4
2 embryo MP:0005380 9.88 EYA1 KIF26B OTX1 PAX2 PAX6 SALL4
3 mortality/aging MP:0010768 9.8 EYA1 KIF26B OTX1 PAX2 PAX6 SALL4
4 hearing/vestibular/ear MP:0005377 9.77 EYA1 OTX1 PAX2 PAX6 SALL4
5 craniofacial MP:0005382 9.76 EYA1 OTX1 PAX6 SALL4
6 digestive/alimentary MP:0005381 9.73 EYA1 OTX1 PAX6 SALL4
7 nervous system MP:0003631 9.65 SALL4 EYA1 OTX1 PAX2 PAX6
8 renal/urinary system MP:0005367 9.55 EYA1 KIF26B PAX2 PAX6 SALL4
9 reproductive system MP:0005389 9.35 EYA1 OTX1 PAX2 PAX6 SALL4
10 vision/eye MP:0005391 9.02 EYA1 OTX1 PAX2 PAX6 SALL4

Drugs & Therapeutics for Papillorenal Syndrome

Search Clinical Trials , NIH Clinical Center for Papillorenal Syndrome

Genetic Tests for Papillorenal Syndrome

Genetic tests related to Papillorenal Syndrome:

# Genetic test Affiliating Genes
1 Renal Coloboma Syndrome 28 PAX2

Anatomical Context for Papillorenal Syndrome

MalaCards organs/tissues related to Papillorenal Syndrome:

38
Kidney, Eye, Skin, Retina

Publications for Papillorenal Syndrome

Articles related to Papillorenal Syndrome:

(show all 48)
# Title Authors Year
1
Rethinking genotype-phenotype correlations in papillorenal syndrome: a case report on an unusual congenital camptodactyly and skeletal deformity with a heterogeneous PAX2 mutation of hexanucleotide duplication. ( 29054766 )
2018
2
Three New<i>PAX2</i>Gene Mutations in Patients with Papillorenal Syndrome. ( 29339962 )
2017
3
Bilateral Optic Nerve Coloboma and Macular Schisis in Papillorenal Syndrome. ( 27107352 )
2016
4
Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome. ( 26571382 )
2015
5
Retinoschisis and outer retinal hole formation in a patient with papillorenal syndrome. ( 25932727 )
2015
6
Association between graves' disease and renal coloboma syndrome: a case report. ( 23966757 )
2013
7
Papillorenal syndrome in a family with unusual complications. ( 23686327 )
2013
8
Papillorenal syndrome with de novo reciprocal translocation t(2;15) (q31; q26). ( 24032291 )
2013
9
Renal coloboma syndrome associated with double- chambered right ventricle. ( 23443859 )
2013
10
Successful ABO-Incompatible Living-Donor Renal Transplant Without Splenectomy For Renal Coloboma Syndrome: A Case Report. ( 23902562 )
2013
11
Alport-like glomerular basement membrane changes with renal-coloboma syndrome. ( 22350371 )
2012
12
Typical renal-coloboma syndrome phenotype in a patient with a submicroscopic deletion of the PAX2 gene. ( 22581475 )
2012
13
Discordant phenotype in monozygotic twins with renal coloboma syndrome and a PAX2 mutation. ( 22660956 )
2012
14
A novel interstitial deletion of 10q24.2q24.32 in a patient with renal coloboma syndrome. ( 22361651 )
2012
15
Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database. ( 22213154 )
2012
16
Renal coloboma syndrome. ( 21654726 )
2011
17
Clinical utility gene card for: renal coloboma (Papillorenal) syndrome. ( 21326282 )
2011
18
A surviving case of papillorenal syndrome with the phenotype of Potter sequence. ( 21696512 )
2011
19
Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human. ( 20221250 )
2010
20
A case of renal-coloboma syndrome associated with mental developmental delay exhibiting a novel PAX2 gene mutation. ( 19954729 )
2009
21
Papillorenal syndrome after Beta-interferon treatment in pregnancy. ( 19839859 )
2009
22
Bilateral macular detachment caused by bilateral optic nerve malformation in a papillorenal syndrome due to a new PAX2 mutation. ( 28221651 )
2008
23
Bilateral macular detachment caused by bilateral optic nerve malformation in a papillorenal syndrome due to a new PAX2 mutation. ( 18609495 )
2008
24
Diagnosing papillorenal syndrome: see the optic papilla. ( 18512081 )
2008
25
Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at Exon 8 is associated with a highly variable phenotype. ( 17269592 )
2007
26
A clinico-genetic study of renal coloboma syndrome in children. ( 17541647 )
2007
27
Abnormal optic discs and renal failure: papillorenal syndrome. ( 17083547 )
2006
28
Early diagnosis of the papillorenal syndrome by optic disc morphology. ( 16148630 )
2005
29
De novo insG619 mutation in PAX2 gene in a Japanese patient with papillorenal syndrome. ( 15808183 )
2005
30
Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk. ( 14747376 )
2004
31
Optic nerve dysplasia and renal insufficiency in a family with a novel PAX2 mutation, Arg115X: further ophthalmologic delineation of the renal-coloboma syndrome. ( 14566649 )
2003
32
Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice mimics the renal-coloboma syndrome. ( 14569086 )
2003
33
Papillorenal syndrome in a Brazilian family. ( 12470164 )
2002
34
[Renal-coloboma syndrome]. ( 12410411 )
2002
35
Multifocal visual evoked potentials and multifocal electroretinograms in papillorenal syndrome. ( 12049607 )
2002
36
Renal-coloboma syndrome: report of a novel PAX2 gene mutation. ( 11730657 )
2001
37
Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity. ( 11297491 )
2001
38
Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family. ( 11241473 )
2001
39
Renal-coloboma syndrome in a Brazilian family. ( 11594973 )
2001
40
Renal coloboma syndrome. ( 11581073 )
2001
41
PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism. ( 11093271 )
2000
42
Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome. ( 10533062 )
1999
43
Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. ( 10466411 )
1999
44
Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330). ( 9760197 )
1998
45
Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations. ( 9106533 )
1997
46
The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. ( 8943028 )
1996
47
Mutation of PAX2 in two siblings with renal-coloboma syndrome. ( 8589702 )
1995
48
Renal Coloboma Syndrome ( 20301624 )
1993

Variations for Papillorenal Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Papillorenal Syndrome:

71 (show all 17)
# Symbol AA change Variation ID SNP ID
1 PAX2 p.Gly76Ser VAR_003789 rs79555199
2 PAX2 p.Gly25Val VAR_068080
3 PAX2 p.Leu33Arg VAR_068081
4 PAX2 p.Ser61Ile VAR_068082
5 PAX2 p.Ser61Asn VAR_068083
6 PAX2 p.Leu69Pro VAR_068085
7 PAX2 p.Arg71Thr VAR_068086 rs104894170
8 PAX2 p.Gly84Ser VAR_068089
9 PAX2 p.Arg117Pro VAR_068090
10 PAX2 p.Pro130His VAR_068091
11 PAX2 p.Pro130Ser VAR_068092
12 PAX2 p.Asp2Gly VAR_071937
13 PAX2 p.Ile139Val VAR_071941
14 PAX2 p.Ala295Val VAR_071944
15 PAX2 p.Leu296Pro VAR_071945
16 PAX2 p.Pro298Ser VAR_071946 rs893370744
17 PAX2 p.Thr329Ala VAR_071947

ClinVar genetic disease variations for Papillorenal Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PAX2 NM_003990.4(PAX2): c.561delC (p.Asn188Metfs) deletion Pathogenic rs77777862 GRCh37 Chromosome 10, 102541067: 102541067
2 PAX2 NM_003990.4(PAX2): c.130_151del22 (p.Leu44Profs) deletion Pathogenic rs76675173 GRCh37 Chromosome 10, 102509589: 102509610
3 PAX2 PAX2, 6-BP DEL deletion Pathogenic
4 PAX2 NM_003990.4(PAX2): c.226G> A (p.Gly76Ser) single nucleotide variant Pathogenic rs79555199 GRCh37 Chromosome 10, 102510464: 102510464
5 PAX2 NM_000278.3(PAX2): c.221_226dupAGACCG (p.Thr75_Gly76insGluThr) duplication Pathogenic rs387906530 GRCh37 Chromosome 10, 102510459: 102510464
6 PAX2 NM_003990.4(PAX2): c.76delG (p.Val26Cysfs) deletion Pathogenic rs75462234 GRCh37 Chromosome 10, 102509535: 102509535
7 PAX2 NM_003990.4(PAX2): c.75_76dupGG (p.Val26Glyfs) duplication Pathogenic rs77453353 GRCh37 Chromosome 10, 102509534: 102509535
8 PAX2 NM_003990.4(PAX2): c.1023C> A (p.Tyr341Ter) single nucleotide variant Pathogenic rs78122364 GRCh37 Chromosome 10, 102584439: 102584439
9 PAX2 NM_000278.4(PAX2): c.706C> T (p.Gln236Ter) single nucleotide variant Pathogenic rs75399846 GRCh38 Chromosome 10, 100806519: 100806519
10 PAX2 NM_003990.4(PAX2): c.76dupG (p.Val26Glyfs) duplication Pathogenic rs77453353 GRCh38 Chromosome 10, 100749778: 100749778

Copy number variations for Papillorenal Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 38428 10 102495457 102579688 Deletion PAX2 Renal-coloboma syndrome

Expression for Papillorenal Syndrome

Search GEO for disease gene expression data for Papillorenal Syndrome.

Pathways for Papillorenal Syndrome

GO Terms for Papillorenal Syndrome

Cellular components related to Papillorenal Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein complex GO:0043234 9.13 EYA1 PAX2 SALL4
2 protein-DNA complex GO:0032993 8.62 EYA1 PAX2

Biological processes related to Papillorenal Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.85 EYA1 OTX1 PAX2 PAX6 SALL4
2 positive regulation of transcription, DNA-templated GO:0045893 9.73 EYA1 PAX2 PAX6
3 multicellular organism development GO:0007275 9.65 EYA1 KIF26B OTX1 PAX2 PAX6
4 transcription by RNA polymerase II GO:0006366 9.62 OTX1 PAX2 PAX6 SALL4
5 axonogenesis GO:0007409 9.58 PAX2 PAX6
6 animal organ morphogenesis GO:0009887 9.57 EYA1 PAX6
7 anterior/posterior pattern specification GO:0009952 9.55 OTX1 PAX6
8 positive regulation of transcription by RNA polymerase II GO:0045944 9.55 EYA1 OTX1 PAX2 PAX6 SALL4
9 neural tube closure GO:0001843 9.54 PAX2 SALL4
10 forebrain development GO:0030900 9.52 OTX1 PAX6
11 camera-type eye development GO:0043010 9.51 PAX2 PAX6
12 positive regulation of epithelial cell proliferation GO:0050679 9.49 EYA1 PAX2
13 cell fate commitment GO:0045165 9.48 EYA1 PAX6
14 branching involved in ureteric bud morphogenesis GO:0001658 9.43 EYA1 PAX2
15 cochlea morphogenesis GO:0090103 9.4 EYA1 PAX2
16 cell fate determination GO:0001709 9.37 PAX2 PAX6
17 mesodermal cell fate specification GO:0007501 8.96 EYA1 PAX2
18 inner ear morphogenesis GO:0042472 8.8 EYA1 OTX1 PAX2

Molecular functions related to Papillorenal Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.33 OTX1 PAX6 SALL4
2 transcription factor binding GO:0008134 9.13 PAX2 PAX6 SALL4
3 transcription regulatory region DNA binding GO:0044212 8.8 PAX2 PAX6 SALL4

Sources for Papillorenal Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....