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European Journal of Human Genetics :... Dec 2011Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The... (Review)
Review
Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, frequently called optic nerve coloboma or morning glory anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst and pigmentary macular dysplasia. The kidney abnormalities consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than the normal number of glomeruli and these glomeruli are enlarged, a finding called oligomeganephronia. Consequences of the ocular malformations include decreased visual acuity and retinal detachment. Consequences of the renal hypodysplasia include hypertension, proteinuria and renal insufficiency that frequently progresses to end-stage kidney disease. High frequency hearing loss has been reported. Autosomal dominant mutations in PAX2 can be identified in nearly half of all patients with clinical findings suggestive of RCS, however, the majority of published cases have mutations in PAX2, thus biasing the known information about the phenotype.
Topics: Animals; Coloboma; Disease Models, Animal; Genetic Counseling; Genetic Testing; Humans; Mutation; PAX2 Transcription Factor; Renal Insufficiency; Vesico-Ureteral Reflux
PubMed: 21654726
DOI: 10.1038/ejhg.2011.102 -
Pediatric Nephrology (Berlin, Germany) May 2024Renal ciliopathies are a common cause of kidney failure in children and adults, and this study reviewed their ocular associations. Genes affected in renal ciliopathies... (Review)
Review
Renal ciliopathies are a common cause of kidney failure in children and adults, and this study reviewed their ocular associations. Genes affected in renal ciliopathies were identified from the Genomics England Panels. Ocular associations were identified from Medline and OMIM, and the genes additionally examined for expression in the human retina ( https://www.proteinatlas.org/humanproteome/tissue ) and for an ocular phenotype in mouse models ( http://www.informatics.jax.org/ ). Eighty-two of the 86 pediatric-onset renal ciliopathies (95%) have an ocular phenotype, including inherited retinal degeneration, oculomotor disorders, and coloboma. Diseases associated with pathogenic variants in ANK6, MAPKBP1, NEK8, and TCTN1 have no reported ocular manifestations, as well as low retinal expression and no ocular features in mouse models. Ocular abnormalities are not associated with the most common adult-onset "cystic" kidney diseases, namely, autosomal dominant (AD) polycystic kidney disease and the AD tubulointerstitial kidney diseases (ADTKD). However, other kidney syndromes with cysts have ocular features including papillorenal syndrome (optic disc dysplasia), Hereditary Angiopathy Nephropathy, Aneurysms and muscle Cramps (HANAC) (tortuous retinal vessels), tuberous sclerosis (retinal hamartomas), von Hippel-Lindau syndrome (retinal hemangiomas), and Alport syndrome (lenticonus, fleck retinopathy). Ocular abnormalities are associated with many pediatric-onset renal ciliopathies but are uncommon in adult-onset cystic kidney disease. However the demonstration of ocular manifestations may be helpful diagnostically and the features may require monitoring or treatment.
Topics: Adult; Child; Animals; Mice; Humans; Kidney; Retinal Diseases; Nephritis, Hereditary; Retina; Kidney Diseases, Cystic; Ciliopathies
PubMed: 37644229
DOI: 10.1007/s00467-023-06096-5 -
Veterinary Ophthalmology Mar 2020To examine the in vivo microanatomy of retinal folds and geographic lesions in dogs with acquired or inherited retinal dysplasia.
PURPOSE
To examine the in vivo microanatomy of retinal folds and geographic lesions in dogs with acquired or inherited retinal dysplasia.
MATERIAL AND METHODS
Thirteen dogs had retinal microanatomy evaluation under general anesthesia using cSLO/sdOCT; two eyes had noninherited multifocal retinal folds, five had inherited multifocal retinal folds (drd1 or drd2), and 10 geographic retinal dysplasia. Retinas from two drd2 carrier dogs were examined by histology and immunohistochemistry (IHC) after in vivo imaging.
RESULTS
Retinal folds are the common feature of acquired focal/multifocal or geographic retinal dysplasia, are indistinguishable structurally from those associated with syndromic oculoskeletal dysplasia, and represent outer nuclear layer invaginations and rosettes visible by sdOCT. In dogs heterozygous for oculoskeletal dysplasia, the folds form clusters in a perivascular distribution along superior central vessels. IHC confirmed photoreceptor identity in the retinal folds. The geographic dysplasia plaques are not focally detached, but have inner retinal disorganization and intense autofluorescence in cSLO autofluorescence mode that is mainly limited to the geographic lesion, but is not uniform and in some extends beyond the plaques.
CONCLUSION
We propose that the autofluorescent characteristic of the geographic lesions is associated with an inner retinal disruption associated with perivascular or infiltrating macrophages and phagocytosis of cellular debris. As well, we suggest restructuring the examination forms to distinguish the folds that are sporadically distributed from those that have a perivascular distribution as the latter likely represent carriers for drd. In this latter group, DNA testing would be a helpful tool to provide specific breeding advice.
Topics: Animals; Dog Diseases; Dogs; Female; Genetic Predisposition to Disease; Male; Retinal Dysplasia
PubMed: 31746146
DOI: 10.1111/vop.12725