retinal vascular anomalies

Papillorenal Syndrome

Clinical Characteristics
Ocular Features: 

Optic disc dysplasia is the ocular hallmark of this disease.  The nerve head often has the appearance of the ‘morning glory’ anomaly but some authors describe this as a coloboma or an optic pit.  Iris colobomas do not occur and only two patients have been reported with retinal colobomas.  There may be severe visual impairment due to the dysplastic optic nerves, but macular and retinal malformations may also contribute.  Other patients have near normal vision. The central retinal vessels are anomalous or even absent with the multiple smaller vessels exiting from the periphery of the disc.  The retina and fovea have been described as hypoplastic and have pigmentary changes. There is often a superonasal visual field defect.  Retrobulbar optic nerve cysts, high myopia, and posterior staphylomas have been noted in a few patients.  As in most autosomal dominant disorders, there is considerable clinical variability.

Systemic Features: 

Kidney dysfunction leading to chronic renal disease is the most common systemic abnormality in this condition.  It can occur at any age.  This often but not always is the result of pyelonephritis secondary to urogenital anomalies causing vesicoureteral reflux.  Other renal disease such as cystic renal hypoplasia may be present.  Other patients have only mild kidney malfunction with proteinuria and elevated serum creatinine.  A minority of patients has a mild high frequency hearing loss and rare individuals have CNS malformations.  Joint laxity and soft skin have also been described.

Genetics

This is an autosomal dominant disorder resulting from heterozygous mutations in the PAX2 gene (10q24.31). Nearly half of reported cases are sporadic secondary to new mutations.  Yet other well-studied families do not have mutations in the PAX2 gene suggesting genetic heterogeneity.

Optic nerve colobomas (120430) may also result from mutations in PAX6.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Kidney failure may require renal transplantation.  Vesicoureteral reflex has been treated with ureteral reimplantation.  Low vision aids may be beneficial in some patients.  Renal hypertension requires treatment.

References
Article Title: 

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus specific database

Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Birk Jensen U, Cochat P, Decramer S, Dixon J, Drouin R, Falk M, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morini?(r)re 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 D, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand D, Eccles M, Schimmenti LA, Heidet L. Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus specific database. Hum Mutat. 2011 Dec 29. [Epub ahead of print]

PubMed ID: 
22213154

Vitreoretinochoroidopathy

Clinical Characteristics
Ocular Features: 

Clinical features are variable in this ocular disorder. Small corneas and shallow anterior chambers have been described in some patients.  Chronic narrow angle glaucoma or frank angle closure glaucoma attacks may occur.  Microphthalmia has been reported but nanophthalmos has not been documented.  Presenile cataracts, nystagmus, and strabismus are sometimes present.  Some patients have normal vision but others have a severe reduction in acuity, even blindness.

The vitreous is often liquefied and some patients have a fibrillary vitreous with pleocytosis.  Preretinal white dots and neovascularization are often seen, even in children.  Peripapillary atrophy may extend to the macula which may have cystic edema.  Peripherally in annular fashion there is often a pigmentary retinopathy extending to an equatorial demarcation line at the posterior border.  The ERG is usually moderately abnormal with evidence of rod and cone dystrophy generally in older patients in which some degree of dyschromatopsia is often present.  Some patients demonstrate a concentric reduction in visual field that progresses with age.  A reduced light/dark ratio has also been documented in several families.  Retinal detachment is a risk.  A posterior staphylomas has been noted in a few patients. 

Systemic Features: 

No systemic abnormalities have been reported. 

Genetics

This is an autosomal dominant disorder resulting from mutations in BEST1 (11q13), which is also responsible for Best vitelliform macular dystrophy (153700). 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No prophylactic treatment has been reported but patients need lifelong monitoring to detect and treat glaucoma, retinal neovascularization, and detachments. 

References
Article Title: 

Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)

Yardley J, Leroy BP, Hart-Holden N, Lafaut BA, Loeys B, Messiaen LM, Perveen R, Reddy MA, Bhattacharya SS, Traboulsi E, Baralle D, De Laey JJ, Puech B, Kestelyn P, Moore AT, Manson FD, Black GC. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3683-9.

PubMed ID: 
15452077
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