Clinical Diagnosis

The diagnosis of renal coloboma syndrome (papillorenal syndrome) is based on clinical findings in the kidneys and eyes. Formal clinical diagnostic criteria have not been established.

Renal findings

• Hypoplastic kidneys characterized on ultrasound examination by hypoplasia (small size for age) and hyperechogenicity [Schimmenti et al 1995]. Renal hypoplasia is usually bilateral, although marked variability between kidneys can be observed, e.g., one small or absent kidney and one of normal size.

• Renal hypodysplasia (RHD), characterized histologically by reduced number of nephrons, small kidney size, and disorganized renal tissue [Weber et al 2006]

• Multicystic dysplastic kidney, characterized histologically by cystic or dysplastic kidneys, exhibiting some degree of disorganization of the kidney architecture. Multicystic dysplastic kidneys are observed in about 10% of individuals with renal coloboma syndrome [Fletcher et al 2005].

• Oligomeganephronia, characterized histologically by fewer than normal glomeruli that are enlarged in size [Salomon et al 2001]

• Renal insufficiency and end-stage renal disease (ESRD)

• Vesicoureteral reflux

Eye findings

• The primary eye finding is dysplasia of the optic nerve, a phenotypic spectrum of disc malformations that ranges from severe to mild.

  • The most severe form is characterized by an apparently enlarged disc in which the vessels that normally exit from the center of the disc, exit instead from the periphery [Schimmenti et al 2003]. Associated abnormalities may include redundant fibroglial tissue.

  • A milder form is an optic nerve pit characterized by a relatively localized (or sub-total) excavation of the optic disc.

  • The mildest form is the exiting of the retinal vessels from the periphery of the disc without malformation of the disc itself.

Note: (1) Differences exist in the terminology used to designate dysplasia of the optic nerve with abnormal passage of retinal vessels from the periphery of the optic nerve head. Some ophthalmologists refer to this finding as congenital excavation of the optic nerve and others "optic nerve coloboma." However, the use of the term coloboma can be confusing in this setting because coloboma usually refers to non-closure of the optic fissure during the seventh week of gestation, resulting in typical uveal colobomas (iris and retinal colobomas). The developmental mechanism underlying the optic nerve abnormalities observed in renal coloboma syndrome is unknown and is under investigation in animal models. (2) Some have described one of the optic nerve findings in this syndrome as "morning glory anomaly," defined as a wide and deeply excavated optic nerve with a central glial tuft and all vessels exiting abnormally at the periphery of the nerve, giving the appearance of a morning glory flower. However, it is debated whether use of the term morning glory anomaly is appropriate to describe the optic nerve malformation in renal coloboma syndrome because it may be a misnomer for the dysplasia of the optic nerve typically seen in this syndrome.

• Less common associated eye malformations in individuals with documented mutations in PAX2 [Sanyanusin et al 1995, Schimmenti et al 1995, Schimmenti et al 1999, Amiel et al 2000, Dureau et al 2001, Schimmenti et al 2003] include the following:

  • Scleral staphyloma, defined as posterior bulging of the eye wall (sclera) is likely a secondary thinning of neural-crest-derived tissue in the area of the anatomically-abnormal optic nerve head. Retinal thinning and myopia are secondary to enlargement of the globe.

  • Optic nerve cyst, a cystic dilatation of the optic nerve posterior to the globe, is observed by cranial imaging, such as MRI. The cyst likely results from incomplete regression of the primordial optic stalk, followed by accumulation of fluid in its potential space.

• Retinal coloboma, defined as absence of retinal tissue in the nasal ventral portion of the retina resulting from failure of closure of the uveal tract. This is a rare finding, observed in two of 50 persons with PAX2 mutations [Schimmenti et al 1997, Schimmenti et al 1999].

  Note: (1) Some individuals with renal coloboma syndrome may not have vision loss and hence, examination of the fundus through a dilated pupil may be necessary to observe optic nerve abnormalities [Chung et al 2001]. (2) Iris coloboma has not been observed in persons with PAX2 mutations.

Molecular Genetic Testing

Gene.   PAX2 is the only gene known to be associated with renal coloboma syndrome.

Other loci.  It is estimated that about half of individuals with renal coloboma syndrome do not have a known genetic basis [Dureau et al 2001, Parsa et al 2001]. Thus, genetic heterogeneity is a possibility.

Clinical testing

• Sequence analysis.  Mutations in PAX2 have been identified in 50% of persons with renal coloboma syndrome [Dureau et al 2001].

Table 1. Summary of Molecular Genetic Testing Used in Renal Coloboma Syndrome

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Test Method	Mutations Detected	Mutation Detection Frequency  1	Test Availability
Sequence analysis	PAX2 point mutations/small deletions/duplications	~50%	Clinical

Test Availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1.  Proportion of affected individuals with a mutation(s) as classified by gene/locus, phenotype, population group, genetic mechanism, and/or test method

Interpretation of test results.  For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

Confirmation of the diagnosis in a proband.   PAX2 molecular genetic testing should be considered in a proband who has eye findings and/or renal findings of renal coloboma syndrome.

Predictive testing for at-risk family members could be used to clarify the genetic status of at-risk relatives in order to begin expectant management of renal disease and/or eye disease. Predictive testing requires prior identification of the disease-causing mutation in an affected family member.

Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutation in an affected family member.

Genetically Related (Allelic) Disorders

Although Nishimoto et al (2001) suggested that the finding of apparently isolated renal hypoplasia in one proband with a PAX2 mutation could represent allelic heterogeneity in PAX2 mutations, data are insufficient at this time to draw such conclusions (see Clinical Description).

Natural History

Renal coloboma syndrome is characterized by hypodysplastic kidneys and optic nerve abnormalities (most commonly optic nerve dysplasia) with or without optic nerve or retinal coloboma [Schimmenti et al 2003].

The clinical findings vary even within families, with some family members having either renal manifestations or optic nerve abnormalities and others having both.

In some instances a detailed eye examination is necessary to reveal the ocular findings of renal coloboma syndrome in individuals presenting with characteristic renal findings. For example:

• In 20 probands ascertained for apparently isolated renal hypoplasia/dysplasia without known eye malformations, Nishimoto et al (2001) found PAX2 mutations in two; on ophthalmologic examination, one of the two PAX2-positive probands had eye findings consistent with renal coloboma syndrome.

• Of nine probands ascertained for oligomeganephronia by Salomon et al (2001), three were found to have a PAX2 mutation. On further evaluation all three with a PAX2 mutation were found to have minor eye findings consistent with renal coloboma syndrome; none had visual impairment.

• In an individual who had undergone renal transplantation for end-stage renal disease (ESRD), an optic nerve coloboma was found incidentally. Subsequently a mutation in PAX2 was identified [Chung et al 2001].

Conversely, in a family ascertained because of eye abnormalities, Parsa et al (2001) found renal hypoplasia in several members and previously unsuspected ESRD in one family member. Molecular genetic testing for PAX2 was carried out, but no mutations were identified.

Renal disease.  ESRD occurs in 33% of persons with PAX2 mutations. ESRD occurs in almost 100% of individuals with a PAX2 mutation and renal hypoplasia.

Renal insufficiency/failure can occur at any age. A fetus with a PAX2 mutation had oligohydramnios and absent kidneys resulting in a Potter syndrome phenotype [Ford et al 2001]. Newborns have been reported with oligohydramnios and renal failure. Other affected individuals have not developed renal failure until the sixth decade [Schimmenti et al 2003].

The natural history of vesicoureteral reflux varies: in some individuals ureteral reimplantation has been required [Schimmenti et al 1995], while in others the reflux has spontaneously resolved [Ford et al 2001].

Eye abnormalities.  Visual acuity ranges from near normal to severely impaired, with a reduction in visual acuity of one or both eyes present in 75% of affected individuals. Other findings can include nystagmus and strabismus.

The natural history of visual acuity in individuals with renal coloboma syndrome has not been prospectively studied. Of the 60 individuals with renal coloboma syndrome reported to date, visual acuity deteriorated in one person as a result of retinal detachment [Ford et al 2001]. One person previously reported acute vision loss resulting in a change of visual acuity from 20/80 to light perception only [Schimmenti et al 1995]; however, the cause of vision loss was unexplained as there was no evidence of detachment or macular changes [Schimmenti, unpublished observation].

Other.  Less commonly reported findings in affected individuals include high-frequency hearing loss, soft skin, and ligamentous laxity.

Genotype-Phenotype Correlations

PAX2 mutations in exons 2, 3, and 4, the exons that encode the DNA binding (paired) domain, are associated with both the ocular and renal manifestations of renal coloboma syndrome, although individuals with milder ocular manifestations have been reported with mutations in these exons.

PAX2 mutations in exons 7 and 9 are typically associated with renal hypoplasia/dysplasia and milder ocular manifestations [Porteous et al 2000, Nishimoto et al 2001].

Penetrance

In individuals with mutations in PAX2, the penetrance of eye malformations is greater than 90% and the penetrance of abnormalities in kidney morphogenesis or function is approximately 65%.

Anticipation

Anticipation has not been observed in this condition.

Nomenclature

Renal coloboma syndrome may be a misnomer because the eye malformation most commonly seen in this disorder is optic nerve dysplasia, not the eye malformations associated with typical uveal coloboma.

Other terms that have been used for renal coloboma syndrome:

• Coloboma-ureteral-renal syndrome

• Optic nerve coloboma with renal disease

• Coloboma of the optic nerve with renal disease

• Optic coloboma-vesicoureteral reflux-renal anomalies

Prevalence

The prevalence of renal coloboma syndrome is unknown. More than 60 affected individuals have been reported.

In a study of 20 persons with renal hypoplasia/dysplasia, two were found to have mutations in PAX2 [Nishimoto et al 2001].

In a study of 99 unrelated individuals with renal hypodysplasia, four were found to have PAX2 mutations [Weber et al 2006].

In a study of 100 persons with colobomatous eye defects, only one was found to have a PAX2 mutation; this person also had renal disease [Cunliffe et al 1998].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with renal coloboma syndrome, the following are recommended:

• Evaluation of renal structure and function including renal ultrasound examination

• Measurement of serum electrolyte concentrations, BUN, and creatinine

• Urinalysis to evaluate for the presence of blood and protein

• Evaluation for vesicoureteral reflux, if clinically indicated

• Dilated eye examination

• Audiologic assessment (See Deafness and Hereditary Hearing Loss Overview for details of audiologic assessment.)

Treatment of Manifestations

A team approach that includes specialists in ophthalmology, nephrology, medical genetics, and audiology is recommended.

Management is focused on preventing complications of end-stage renal disease (ESRD) and/or vision loss resulting from retinal detachment.

Treatment of hypertension, and/or vesicoureteral reflux, if present, may preserve renal function.

ESRD is treated with renal replacement therapy (i.e., dialysis and/or renal transplantation).

Low vision experts can assist with adaptive functioning of those with significant vision loss.

Prevention of Secondary Complications

Prevention of retinal detachment in those with congenital optic nerve abnormalities includes close follow up with an ophthalmologist and use of protective lenses.

Surveillance

• Follow-up by a nephrologist to monitor renal function and blood pressure

• Follow-up by an ophthalmologist to monitor vision. Any change in vision could indicate a retinal detachment and should be treated as a medical emergency.

Testing of Relatives at Risk

At-risk relatives should be offered molecular genetic testing if a mutation in PAX2 has been identified in an affected family member.

For those in whom a mutation in PAX2 cannot be identified, dilated ophthalmologic examination and renal ultrasound examination, tests of renal function, urinalysis, and blood pressure evaluation should be performed.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Other

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.

Mode of Inheritance

Renal coloboma syndrome is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

• Approximately half of the individuals diagnosed with renal coloboma syndrome have an affected parent and half have the disorder as the result of a new gene mutation.

• If the disease-causing mutation found in the proband cannot be detected in the DNA extracted from the leukocytes of either parent, two possible explanations are germline mosaicism in a parent or a de novo mutation in the proband. Germline mosaicism has been reported in renal coloboma syndrome.

• Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include molecular genetic testing if the PAX2 mutation has been identified in the proband, dilated ophthalmologic evaluation, and renal evaluation. Evaluation of parents may determine that one is affected but has escaped previous diagnosis because of failure by health care professionals to recognize the syndrome and/or a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed until appropriate evaluations have been performed.

Note: (1) Although nearly half of the individuals diagnosed with renal coloboma syndrome have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or reduced penetrance. (2) If the parent is the individual in whom the mutation first occurred s/he may have somatic mosaicism for the mutation and may be mildly/minimally affected. A family with documented germline mosaicism has been reported [Amiel et al 2000].

Sibs of a proband

• The risk to the sibs of the proband depends upon the genetic status of the proband's parents.

• If a parent of the proband is affected, the risk to the sibs is 50%.

• When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low, but greater than that of the general population because germline mosaicism has been documented for this disorder.

Offspring of a proband.  Each child of an individual with renal coloboma syndrome has a 50% chance of inheriting the mutation.

Other family members of a proband.  The risk to other family members depends upon the status of the proband's parents. If a parent is found to be affected, his or her family members are at risk .

Related Genetic Counseling Issues

See Testing of Relatives at Risk for information on testing at-risk relatives for the purpose of early diagnosis and treatment.

Considerations in families with an apparent de novo mutation.  When neither parent of a proband with an autosomal dominant condition has the disease-causing mutation or clinical evidence of the disorder, it is likely that the proband has a de novo mutation. However, possible non-medical explanations including alternate paternity or undisclosed adoption could also be explored.

Family planning.  The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.

DNA banking.  DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%, molecular genetic testing is available on a research basis only, or some of the genes in which disease-causing mutations occur have not been identified. See DNA Banking for a list of laboratories offering this service.

Prenatal Testing

Molecular genetic testing.  Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. The disease-causing allele of an affected family member must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Prenatal fetal ultrasound examination of an at-risk pregnancy or known affected pregnancy may be used during the later stages of pregnancy to detect renal malformations that could affect the well-being of the newborn or warrant further evaluation after birth.

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified in an affected family member. For laboratories offering PGD, see .

Molecular Genetic Pathogenesis

The pattern of abnormalities in renal coloboma syndrome is consistent with the known expression pattern of PAX2 during embryonic development. Porteous et al (2000) and Torban et al (2000) have demonstrated in mouse models and tissue culture that normal biallelic PAX2 dosage is needed to prevent programmed cell death.

Normal allelic variants: PAX2 is encoded in 12 exons.

Pathologic allelic variants: See Table 2 (pdf).

Normal gene product: Paired box protein PAX-2 is a DNA-binding protein characterized by an N-terminal paired domain, a bipartite helix-loop-helix domain, a small octapeptide domain, a truncated homeodomain, and a proline/serine/threonine-rich C-terminal domain. Multiple isoforms, by alternative splicing of at least exons 6 and 10, exist.

Abnormal gene product: The majority of identified missense, nonsense, and protein truncating mutations occur in the paired domain of the protein, apparently resulting in a null protein product or haploinsufficiency.

Literature Cited

1. Amiel J, Audollent S, Joly D, Dureau P, Salomon R, Tellier AL, Auge J, Bouissou F, Antignac C, Gubler MC, Eccles MR, Munnich A, Vekemans M, Lyonnet S, Attie-Bitach T. PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism. Eur J Hum Genet. 2000;8:820–6. [PubMed: 11093271]
2. Azuma N, Yamaguchi Y, Handa H, Tadokoro K, Asaka A, Kawase E, Yamada M. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am J Hum Genet. 2003;72:1565–70. [PMC free article: PMC1180317] [PubMed: 12721955]
3. Bohn S, Thomas H, Turan G, Ellard S, Bingham C, Hattersley AT, Ryffel GU. Distinct molecular and morphogenetic properties of mutations in the human HNF1beta gene that lead to defective kidney development. J Am Soc Nephrol. 2003;14:2033–41. [PubMed: 12874457]
4. Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R III. Renal-coloboma syndrome: report of a novel PAX2 gene mutation. Am J Ophthalmol. 2001;132:910–4. [PubMed: 11730657]
5. Cunliffe HE, McNoe LA, Ward TA, Devriendt K, Brunner HG, Eccles MR. The prevalence of PAX2 mutations in patients with isolated colobomas or colobomas associated with urogenital anomalies. J Med Genet. 1998;35:806–12. [PMC free article: PMC1051454] [PubMed: 9783702]
6. Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL. Renal coloboma syndrome. Ophthalmology. 2001;108:1912–6. [PubMed: 11581073]
7. Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M, Juppner H, Alexander SI. Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2. J Am Soc Nephrol. 2005;16:2754–61. [PubMed: 16049068]
8. Ford B, Rupps R, Lirenman D, Van Allen MI, Farquharson D, Lyons C, Friedman JM. Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family. Am J Med Genet. 2001;99:137–41. [PubMed: 11241473]
9. Gentile M, Di Carlo A, Susca F, Gambotto A, Caruso ML, Panella C, Vajro P, Guanti G. COACH syndrome: report of two brothers with congenital hepatic fibrosis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation. Am J Med Genet. 1996;64:514–20. [PubMed: 8862632]
10. Nishimoto K, Iijima K, Shirakawa T, Kitagawa K, Satomura K, Nakamura H, Yoshikawa N. PAX2 gene mutation in a family with isolated renal hypoplasia. J Am Soc Nephrol. 2001;12:1769–72. [PubMed: 11461952]
11. Parsa CF, Silva ED, Sundin OH, Goldberg MF, De Jong MR, Sunness JS, Zeimer R, Hunter DG. Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity. Ophthalmology. 2001;108:738–49. [PubMed: 11297491]
12. 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. Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/- mutant mice. Hum Mol Genet. 2000;9:1–11. [PubMed: 10587573]
13. Salomon R, Tellier AL, Attie-Bitach T, Amiel J, Vekemans M, Lyonnet S, Dureau P, Niaudet P, Gubler MC, Broyer M. PAX2 mutations in oligomeganephronia. Kidney Int. 2001;59:457–62. [PubMed: 11168927]
14. Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont ME, Sullivan MJ, Dobyns WB, Eccles MR. Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet. 1995;9:358–64. [PubMed: 7795640]
15. 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. Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations. Am J Hum Genet. 1997;60:869–78. [PMC free article: PMC1712484] [PubMed: 9106533]
16. Schimmenti LA, Manligas GS, Sieving PA. 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. 2003;24:191–202. [PubMed: 14566649]
17. Schimmenti LA, Pierpont ME, Carpenter BL, Kashtan CE, Johnson MR, Dobyns WB. Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies. Am J Med Genet. 1995;59:204–8. [PubMed: 8588587]
18. Schimmenti LA, Shim HH, Wirtschafter JD, Panzarino VA, Kashtan CE, Kirkpatrick SJ, Wargowski DS, France TD, Michel E, Dobyns WB. Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome. Hum Mutat. 1999;14:369–76. [PubMed: 10533062]
19. Sikora P, Zajaczkowska M, Katska E, Niedzielska G. [A nineteen year observation of a boy with branchio-oto-renal syndrome and chronic renal failure] Pol Merkur Lekarski. 2001;10:291–3. [PubMed: 11434182]
20. Tellier AL, Amiel J, Delezoide AL, Audollent S, Auge J, Esnault D, Encha-Razavi F, Munnich A, Lyonnet S, Vekemans M, Attie-Bitach T. Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome. Am J Med Genet. 2000;93:85–8. [PubMed: 10869107]
21. Torban E, Eccles MR, Favor J, Goodyer PR. PAX2 suppresses apoptosis in renal collecting duct cells. Am J Pathol. 2000;157:833–42. [PMC free article: PMC1885702] [PubMed: 10980123]
22. Verloes A, Lambotte C. Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. Am J Med Genet. 1989;32:227–32. [PubMed: 2929661]
23. Weber S, Moriniere V, Knuppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiene A, Mir S, Montini G, Peco-Antic A, Wuhl E, Zurowska AM, Mehls O, Antignac C, Schaefer F, Salomon R. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol. 2006;17:2864–70. [PubMed: 16971658]

Published Statements and Policies Regarding Genetic Testing

No specific guidelines regarding genetic testing for this disorder have been developed.

Suggested Readings

1. Eccles MR. PAX2 and Renal-Coloboma Syndrome. In: Inborn Errors of Development. Epstein C, Erickson R, Wynshaw-Boris A (Eds). Oxford University Press, San Francisco. 2004
2. Eccles MR, Stayner CK, Bockett N. PAX2 and Renal-Coloboma syndrome. In: The Kidney, From Normal Development to Congenital Abnormalities. Vize PD, Woolf AS, Bard JBL (Eds), Academic Press, London. 2003
3. Horsford DJ, Hanson I, Freund F, McInnes RR, van Heyningen V. Transcription factors in eye disease and ocular development. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B (eds) The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, Chap 240. revised 2002

Revision History

• 8 June 2007 (me) Review posted to live Web site

• 8 December 2006 (las) Original submission