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Renal coloboma syndrome(PAPRS)

MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
Synonyms: CAKUT WITH OR WITHOUT OCULAR ABNORMALITIES; Coloboma of optic nerve with renal disease; CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT WITH OR WITHOUT OCULAR ABNORMALITIES; Optic coloboma, vesicoureteral reflux, and renal anomalies; Optic nerve coloboma with renal disease; Papillorenal syndrome; PAPILLORENAL SYNDROME WITH MILD OCULAR ABNORMALITIES; PAPRS; RENAL-COLOBOMA SYNDROME WITH MACULAR ABNORMALITIES
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Papillorenal syndrome (446449009); Renal coloboma syndrome (446449009)
 
Gene (location): PAX2 (10q24.31)
OMIM®: 120330
Orphanet: ORPHA1475

Disease characteristics

Excerpted from the GeneReview: PAX2-Related Disorder
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis. [from GeneReviews]
Authors:
Matthew A Bower  |  Lisa A Schimmenti  |  Michael R Eccles   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/120330
From GHR
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.Additionally, people with renal coloboma syndrome may have a malformation in the optic nerve, a structure that carries information from the eye to the brain. Optic nerve malformations are sometimes associated with a gap or hole (coloboma) in the light-sensitive tissue at the back of the eye (the retina). The vision problems caused by these abnormalities can vary depending on the size and location of the malformation. Some people have no visual problems, while others may have severely impaired vision.Less common features of renal coloboma syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing loss.  https://ghr.nlm.nih.gov/condition/renal-coloboma-syndrome

Clinical features

Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Microphthalmos
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Vesicoureteral reflux 1
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Joint laxity
MedGen UID:
39439
Concept ID:
C0086437
Pathologic Function
Orbital cyst
MedGen UID:
56359
Concept ID:
C0155285
Finding
Coloboma of optic disc
MedGen UID:
57832
Concept ID:
C0155299
Disease or Syndrome
Retinal coloboma
MedGen UID:
66820
Concept ID:
C0240896
Congenital Abnormality
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Chiari malformation type I
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Chiari malformation type I (CM1) is the protrusion of the cerebellar tonsils through the foramen magnum, defined radiologically as tonsillar descent of 5 mm or more. CM1 is associated with syringomyelia (see 186700) in up to 80% of cases. Although many individuals with CM1 are asymptomatic, the malformation can cause headaches, ocular disturbances, otoneurologic disturbances, lower cranial nerve signs, cerebellar ataxia, or spasticity. Onset of symptoms is usually in the third decade of life (Speer et al., 2003). Since many cases of CM1 are asymptomatic, prevalence estimates may not be accurate. However, a retrospective investigation of brain MRIs reported the prevalence of CM1 to be 1 in 1,280 individuals (Meadows et al., 2000).
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpitation of the skin.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
Multicystic kidney dysplasia
MedGen UID:
811388
Concept ID:
C3714581
Disease or Syndrome
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Chorioretinal atrophy
MedGen UID:
884881
Concept ID:
C4048273
Disease or Syndrome
Atrophy of the choroid and retinal layers of the fundus.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRenal coloboma syndrome
Follow this link to review classifications for Renal coloboma syndrome in Orphanet.

Professional guidelines

PubMed

Bower M, Eccles M, Heidet L, Schimmenti LA
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Feb 16 doi: 10.1038/ejhg.2011.16. PMID: 21326282Free PMC Article

Recent clinical studies

Etiology

Burchell AE, Rodrigues JC, Charalambos M, Ratcliffe LE, Hart EC, Paton JF, Baumbach A, Manghat NE, Nightingale AK
J Clin Hypertens (Greenwich) 2017 Jan;19(1):13-22. Epub 2016 Oct 19 doi: 10.1111/jch.12920. PMID: 27759186
Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Iatropoulos P, Daina E, Mele C, Maranta R, Remuzzi G, Noris M
Pediatr Nephrol 2012 Oct;27(10):1989-93. Epub 2012 Jun 4 doi: 10.1007/s00467-012-2205-x. PMID: 22660956
Gucev ZS, Kirovski I, Jancevska A, Popjordanova N, Tasic V
Ren Fail 2009;31(7):602-5. PMID: 19839859
Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL
Ophthalmology 2001 Oct;108(10):1912-6. PMID: 11581073

Diagnosis

Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, Hara A, Iwata Y, Sakai N, Sugiyama K, Kaneko S, Wada T
PLoS One 2015;10(11):e0142843. Epub 2015 Nov 16 doi: 10.1371/journal.pone.0142843. PMID: 26571382Free PMC Article
Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Laimutis K, Jackson C, Xu X, Warman B, Sarunas R, Andriuskeviciute I, Birute P, Schimmenti LA, Raca G
Am J Med Genet A 2012 Jun;158A(6):1437-41. Epub 2012 May 11 doi: 10.1002/ajmg.a.35342. PMID: 22581475Free PMC Article
Ohtsubo H, Morisada N, Kaito H, Nagatani K, Nakanishi K, Iijima K
Pediatr Nephrol 2012 Jul;27(7):1189-92. Epub 2012 Feb 21 doi: 10.1007/s00467-012-2125-9. PMID: 22350371
Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morinière V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton DW, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand DJ, Eccles M, Schimmenti LA, Heidet L
Hum Mutat 2012 Mar;33(3):457-66. Epub 2012 Jan 31 doi: 10.1002/humu.22020. PMID: 22213154

Therapy

Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Gucev ZS, Kirovski I, Jancevska A, Popjordanova N, Tasic V
Ren Fail 2009;31(7):602-5. PMID: 19839859
Porteous S, Torban E, Cho NP, Cunliffe H, Chua L, McNoe L, Ward T, Souza C, Gus P, Giugliani R, Sato T, Yun K, Favor J, Sicotte M, Goodyer P, Eccles M
Hum Mol Genet 2000 Jan 1;9(1):1-11. PMID: 10587573

Prognosis

Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Alur RP, Vijayasarathy C, Brown JD, Mehtani M, Onojafe IF, Sergeev YV, Boobalan E, Jones M, Tang K, Liu H, Xia CH, Gong X, Brooks BP
PLoS Genet 2010 Mar 5;6(3):e1000870. doi: 10.1371/journal.pgen.1000870. PMID: 20221250Free PMC Article
Gucev ZS, Kirovski I, Jancevska A, Popjordanova N, Tasic V
Ren Fail 2009;31(7):602-5. PMID: 19839859
Shim HH, Nakamura BN, Cantor RM, Schimmenti LA
Mol Genet Metab 1999 Dec;68(4):507-10. doi: 10.1006/mgme.1999.2931. PMID: 10607481

Clinical prediction guides

Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, Hara A, Iwata Y, Sakai N, Sugiyama K, Kaneko S, Wada T
PLoS One 2015;10(11):e0142843. Epub 2015 Nov 16 doi: 10.1371/journal.pone.0142843. PMID: 26571382Free PMC Article
Hoefele J, Gabert M, Heinrich U, Benz K, Rompel O, Rost I, Klein HG, Kunstmann E
Eur J Med Genet 2012 Mar;55(3):211-5. Epub 2012 Jan 31 doi: 10.1016/j.ejmg.2012.01.011. PMID: 22361651
Miyazawa T, Nakano M, Takemura Y, Miyazaki K, Yanagida H, Fujita S, Sugimoto K, Okada M, Takemura T
Clin Nephrol 2009 Dec;72(6):497-500. PMID: 19954729
Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R 3rd
Am J Ophthalmol 2001 Dec;132(6):910-4. PMID: 11730657
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
Am J Hum Genet 1997 Apr;60(4):869-78. PMID: 9106533Free PMC Article

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