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Renal coloboma syndrome
A genetic condition characterized by optic nerve dysplasia and renal hypodysplasia.
ORPHA:1475Classification level: Disorder
Prevalence and prevalence at birth are not known. 177 mutation-positive cases (90 different families) have been reported. The number of mutation-negative individuals with clinical findings of Renal coloboma syndrome (RCS) is not known. There is no ethnic predilection.
RCS is characterized primarily by ocular signs (77%) and renal manifestations (92%). Eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with emergence of the retinal vessels from the disc periphery, frequently called optic nerve coloboma or ''morning glory'' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, reduced corneal diameter, optic nerve cyst, microphthalmia, foveal hypoplasia and pigmentary macular dysplasia. Nystagmus and myopia have also been reported. Consequences include decreased visual acuity, blindness, and retinal detachment. Renal malformations and/or insufficiency are frequently the presenting feature and consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than normal enlarged glomeruli (oligomeganephronia). Other renal findings include multicystic dysplastic kidney and horseshoe kidney. Consequences include hypertension, proteinuria, vesicoureteral reflux, and renal insufficiency that frequently progresses to end-stage renal disease (ESRD). ESRD may present prenatally with severely hypoplastic or dysplastic kidneys and oligohydramnios resulting in fetal loss due to Potter sequence. Patients can progress to stage 5 chronic kidney disease at any age. High frequency (HF) hearing loss is reported in 7% of patients.
Mutations in thePAX2gene (10q24) have been identified in about 1/2 of patients with renal hypodysplasia and abnormalities of the optic nerve. PAX2 mutations have been identified in about 9% of unselected individuals presenting with renal hypoplasia. The genetic basis of the remaining cases is not known.
Formal diagnostic criteria have not been established. However, the disorder should be suspected in patients who have the classical findings of optic nerve dysplasia or coloboma and renal hypodysplasia. Oligomeganephronia is a common histologic finding in renal hypodysplasia but it is not pathognomonic for RCS.
The differential diagnosis includes conditions where colobomas and renal anomalies have been identified such as CHARGE syndrome and Joubert syndrome with oculorenal defect (see these terms). However these disorders generally have other characteristic findings not found in RCS.
Prenatal diagnosis or pre-implantation genetic testing is possible if a clearly pathogenic PAX2 mutation has been identified in a family.
RCS is inherited in an autosomal dominant pattern, though this is complicated by de novo cases, variable expression, incomplete clinical penetrance, and maternal and paternal gonosomal mosaicism.
Management and treatment
Management involves care for the renal and ophthalmologic manifestations. Patient evaluation should include renal function testing, renal ultrasound, urinalysis (proteinuria), blood pressure measurements and evaluation for vesicouretal reflux if clinically indicated. Long-term follow-up by a nephrologist and ophthalmologist are recommended. Low vision experts may also be called upon if needed. Audiologic evaluation for HF hearing loss is indicated as it may affect verbal communication.
Prognosis depends primarily on appropriate specialized treatment. Renal failure can occur at any age requiring dialysis and renal transplantation. Formal longitudinal studies of visual prognosis have not been carried out. However, decreased visual acuity over time has been reported.