Papillorenal syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

Papillorenal syndrome is an autosomal dominant genetic disorder marked by underdevelopment (hypoplasia) of the kidney and colobomas of the optic nerve.^[1]

The other name for papillorenal syndrome is Renal-coloboma syndrome. It is a rare disorder that affects the development of kidneys and the eyes. Affected kidneys are usually small or underdeveloped and may progress to ESRD when the kidneys are no longer able to filter the fluids. One or both the kidneys can be involved In the eyes, various malformations noted are malformed optic nerve and occasionally a hole in the retina known as coloboma. Some of the affected individuals may experience vision loss. Hence the name is given as Renal-coloboma syndrome. Other less common symptoms associated with the disease include vesicoureteral reflux, loose abnormal joints, numerous kidney cysts, and minimal hearing loss.

Papillorenal syndrome for which another term is Renal-coloboma syndrome (RCS). This condition usually consisting of renal anomalies plus optic nerve dysplasia. It is transmitted to future generations in an Autosomal dominant fashion. First clearly described by Weaver al in 1988. In two brothers having ESRD with coloboma in the eyes. In 1995, the association of dominant mutations in the PAX2 gene with RCS was made. It was studied in a two-generation family having renal dysplasia, coloboma of the optic nerve, and also the presence of vesicoureteral reflux. There are different opinions regarding the name of this condition between the observers. Papillorenal syndrome is a combination of renal and ocular anomalies. Eccles and Schimmenti, 1999; Negrisolo et al., 2011 summarized Less common findings associated with the expression of the PAX2 gene in numerous tissues with the disease include hearing loss, CNS anomalies, joint problems, ligament laxity, soft skin.

The known cause of the Papillorenal syndrome is mutation of a copy of the PAX2 gene, a gene which is important in the development of both the eye and the kidney. However, approximately half of patients with Papillorenal syndrome do not have defects in the Pax2. This suggests that other genes play a role in the development of the syndrome, though few downstream effectors of Pax2 have been identified.

The renal coloboma syndrome differentials include most of the disease with renal and ocular anomalies. The numerous important differentials are

• CHARGE Syndrome that includes characteristic five features of the disease including Coloboma, Heart Abnormalities, Choanal Atresia, Growth and development Retardation, Genital Anomalies, Ear and hearing abnormalities. A lot of patients studied under Renal-coloboma syndrome do not have any sort of craniofacial anomalies that are typical of CHARGE Syndrome.
• Branchio-oto-renal syndrome– Renal hypoplasia in these patients makes this an important differential. Pt with PAX6 Mutations – significant overlap with eye findings in patients with PAX6 gene mutation make it an important differential but the renal anomalies that are typical for RCS are absent in these patients.
• COACH Syndrome or Joubert – Important differential due to the presence of both renal abnormalities and coloboma in these patients. However, patients with Renal-coloboma syndrome does not have any developmental abnormality, cerebellar abnormalities, and/or hepatic dysfunction.
• Cat Eye Syndrome – This genetic abnormality is having symptomatic overlap with Renal-coloboma syndrome but the Iris coloboma that is typical for RCS is usually not observed in this disorder.

The Prevalence of the disease and the prevalence at birth is still unknown. In a study conducted in 90 families, they found 177 mutation-positive cases. The number of individuals with mutation-negative is not known in that study. The conclusion derived showed no ethnic predilection for the disease. The major component found in the causation of RCS is PAX2 gene (10q24) in half of the patients with renal and optic nerve abnormalities.

The pathophysiology and the risk factors responsible for the development of Renal-coloboma syndrome is mainly genetic and related to the expression of PAX 2 gene. So the genetic inheritance is the main risk factor or the important determinant in the causation of Renal-coloboma syndrome. This genetic syndrome keeps on clustering in the future generations.

The environmental risk factors that impact the pregnancy like alcohol and some drugs may also contribute to the development of Renal-coloboma syndrome. In conclusion, RCS leads to the abnormal development of organs like kidney and eyes during the pregnancy period. The abnormal development of eyes usually happens in the third trimester during that time the eyes are formed. The abnormalities usually occur due to the impairment in the closure of the optic disc. It usually depends on which specific part or areas of optic fissure fails to close.

RCS is an autosomal dominant disorder characterized by renal and ocular anomalies. It is mainly relate to the PAX2 gene mutations. Epidemiological estimated incidence of coloboma is about 1 in 10,000 births. Only the coloboma itself is estimated to account for 3-11% of blindness in children’s worldwide. Prevalence of disease is still unknown with more than 60 cases are reported in the scientific literature. The most common complications associated are: End stage renal disease, VUR (Vesicoureteral reflux), Eyelid coloboma, Iris coloboma. The prognosis for renal coloboma syndrome depends primarily on the treatment the patient is receiving. The prognosis for renal coloboma syndrome is worse in the presence of congenital anomalies in the patient.

The Ocular and renal anomalies are the most important diagnostic findings representing in patients with characteristic signs and symptoms. Mutation in PAX2 Gene causes optic disc dysplasia and coloboma seen in most of the cases is due to the failure of the choroidal fissure to close. Despite the similarities with coloboma and morning glory anomaly, significant differences exist such that optic disc dysplasia cannot be classified as either one entity. Optic disc dysplasia is noted by an ill-defined inferior excavation, the convoluted origin of the superior retinal vessels, an excessive number of vessels, Infrapapillary pigmentary disturbance, and slight band of retinal elevation adjacent to the disk. Some patients have the normal or near-normal vision, but others have visual impairment associated with the disease, though it is not certain if this is due only to the dysplastic optic nerves, or a possible contribution from macular and retinal malformations. The most common malformation in patients with the syndrome is kidney hypoplasia, which is small and underdeveloped kidneys, often leading to end-stage renal disease (ESRD). Estimates show approximately 10% of children with hypoplastic kidneys are linked to the disease. Many different histological abnormalities have been noted, including a decrease in nephron number associated with hypertrophy, focal segmental glomerulosclerosis, interstitial fibrosis, and tubular atrophy, Multicystic dysplastic kidney.

In most of the patients, the symptoms will differ depending upon a case by case basis. People with a similar disease might have a variable presentation and may not have all the mentioned symptoms. This valuable information is usually collected from the database of Human phenotype Ontology (HPO). The HPO usually collects the symptoms is usually described or mentioned in the various publications and medical resources. The most common manifestations are Enlargement of the optic disc with blood vessels seen coming out from the periphery. Retinal vessels observed in patients with Renal-coloboma syndrome are more in number and tortuosity as compared to see in normal individuals. Less commonly seen anomalies are Scleral staphyloma, Optic nerve cyst, Microphthalmia, Reduced corneal diameters, Foveal hypoplasia, and macular anomalies. The most common renal abnormalities are Renal hypoplasia/ hypo dysplasia kidneys that have a malformed function with a small number of functional glomeruli and can develop ESRD at any point in the disease. Somewhere around 10% of the patients with these kidneys found to have PAX2 gene mutation. Oligomeganephronia Condition seen in some of the patients with Renal-coloboma syndrome and this usually refers to the marked reduction in the number of functionally intact nephrons Compensatory glomerular hypertrophy seen. Glomerulosclerosis and meningeal fibrous deposits are the most common findings seen on histopathology. Multicystic dysplastic kidneys– These are commonly seen in around 10% of the patients reported with RCS. ESRD– End-stage renal disease can happen anytime during the course of the disease.

Lab Findings

The diagnosis of Renal coloboma syndrome is mainly limited to renal and optical anomalies along with the presence of PAX2 gene mutation. So there is not many roles studied in terms of lab findings except doing the genetic workup for PAX2 Gene mutation. Some rare and variant cases of PAX2 gene may also have the Renal histological findings similar to FSGS and that can be further studied and explored in lab conditions.

Other diagnostic studies

The exact criteria for Renal-coloboma syndrome have not been established so far however by seeing the patients clinically the findings of optic nerve coloboma and hypo dysplasia of kidneys are the characteristic abnormalities seen in patients with Renal coloboma syndrome. and out of that nearly half of the patients have a mutation in PAX2 Gene. It was first observed and concluded by Bower and Schimmenti.

The medical management for the patients suffering from Renal-coloboma syndrome consists of a combination of preventive as well as a curative component for the complications or the clinical manifestations happening in patients clinically. The most important component is the clinical evaluation of patient symptoms and signs. The most common evaluation involves a careful assessment of Renal and optical manifestations. The early evaluation and workup should be done in patients to cover up all the possible aspects of clinical manifestations. The prevention of secondary complications is usually important in patients with Renal-coloboma syndrome. The ongoing treatment for hypertension or any other medical illness should be provided to the patients that will further help in the prevention of the development of End-stage renal disease. Evaluation of family members is also important and must be done to detect any asymptomatic individual in the family so he can be managed at the earliest possible time and severe complications in those patients can be avoided.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

Papillorenal syndrome for which another term is Renal-Coloboma Syndrome (RCS). This condition usually consisting of renal anomalies plus optic nerve dysplasia. It is transmitted to future generations in an Autosomal dominant fashion. First clearly described by Weaver al in 1988. In two brothers having ESRD with coloboma in the eyes. In 1995, the association of dominant mutations in PAX2 gene with RCS was made. It was studied in a two-generation family having renal dysplasia, coloboma of the optic nerve, and also the presence of vesicoureteral reflux. There are different opinions regarding the name of this condition between the observers. Papillorenal syndrome is a combination of renal and ocular anomalies. Eccles and Schimmenti, 1999; Negrisolo et al., 2011 summarized Less common findings associated with expression of PAX2 gene in numerous tissues with disease include hearing loss, CNS anomalies, joint problems, ligament laxity, soft skin.

Papillorenal syndrome for which another term used most commonly is Renal-coloboma syndrome(RCS). This condition usually consisting of renal anomalies plus optic nerve dysplasia. It is transmitted to generations in an Autosomal dominant fashion^[1].

Weaver al in 1988 First clearly described papillorenal syndrome. In two brothers having ESRD with coloboma in the eyes.

In 1995, the association of dominant mutations in PAX2 gene with RCS was made. It was studied in a two-generation family having renal dysplasia, coloboma of the optic nerve, and also the presence of vesicoureteral reflux. There are different opinions regarding the name of this condition between the observers.

Rieger in 1977 first reported a family in whom the male died because of chronic kidney disease and bilateral optic disc anomalies. His son on examination also showed eye changes involving macula and retina but on the kidney workup was normal but on the other hand, his daughter was having normal vision with no eye abnormalities suggested from renal failure. This is a variable expression not uncommon in Autosomal dominant syndrome.

Karcher in 1979 described a combined case of father and son from a family showing some eye anomalies and renal disease as well. The eye anomalies found in his son was named morning glory optic disc anomaly. There was a high uncertainty that whether morning glory includes colobomatous defects or its just the abnormal regression of mesodermal embryonic disc structures. Bron et al in 1989 described the same disorder under the term Papillorenal syndrome.

Schimmenti et al. & Sanyanusin et al. in 1995 four individuals ( One father and 3 sons) of having coloboma of the optic nerve, kidney anomalies, and also the presence of vesicoureteral reflux. The father on workup was found to be having normal with respect to the renal function. Although Eye examination showed the presence of myopia a coloboma in the eyes bilaterally. But all 3 sons were having kidneys and eyes affected to a variable extent.

Parsa in 1998 concluded that this is most likely a condition of the dysplastic disc rather than being called coloboma, so the papillorenal syndrome was the most appropriate term designated.

Amiel et al. in 2000 described a family of 3 members with striking ocular phenotypic variability. One of them was having renal hypoplasia along with eye manifestation while the other 2 were having renal anomalies ( Unilateral cystic renal hypoplasia) with optic disc anomalies bilaterally.

According to PubMed search performed in November 2010, The RCS is more common with 131 citations identified when the people searched for the term ‘Renal-coloboma syndrome‘ as compared to only 18 citations that have been identified when people used the search term as ‘Papillorenal syndrome‘. The difference in results and the observation is mainly due to the differences in the explanation or description of phenotypic changes in the eye. For many ophthalmologists, the eye findings are mainly due to the failure of the optic fissure to close during eye development and should be called coloboma. For others, eye manifestation should be regarded as Dysplasia.

Eccles and Schimmenti, 1999; Negrisolo et al., 2011^[2] summarized Less common findings associated with expression of the PAX2 gene in numerous tissues with the disease include hearing loss, CNS anomalies, joint problems, ligament laxity, soft skin.

Schimmenti in 2011- Summarized The ocular and renal anomalies result in a wide range of manifestations. They commonly result in decreased visual activity along with retinal detachment, renal insufficiency, proteinuria, hypertension, which can rapidly go on to develop end-stage renal disease.

Negrisolo et al., 2011; latropoulos at al., 2012.- This disorder has shown a wide variety of familial variability with a variable presentation in different family members. The patients under the category of CAKUT that are ‘congenital anomalies of the kidney and urinary tract‘ present with renal features without remarkable ocular changes, the same is the case with some patients having PAX2 mutations^[3][4]. In these patients the ocular manifestations may be hard to detect without the use of advanced screening techniques or it can be normal.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

The known cause of the Papillorenal syndrome is mutation of a copy of the PAX2 gene, a gene which is important in the development of both the eye and the kidney. However, approximately half of patients with Papillorenal syndrome do not have defects in the Pax2. This suggests that other genes play a role in the development of the syndrome, though few downstream effectors of Pax2 have been identified.

The majority of mutations occur in exons 2,3 and 4, which encode the paired domain and frame shift mutations that lead to a null allele.^[2] The missense mutations appear to disrupt hydrogen bonds, leading to decreased transactivation of Pax2^[3], but do not seem to effect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind to its DNA consensus sequence.^[4] Mutations related to the disease have also been noted in exons 7,8, and 9, with milder phenotypes than the other mutations.^[2]

Pax2 is expressed in the kidney, midbrain, hindbrain, cells in the spinal column, developing ear, and developing eye. Homozygous negative Pax2 mutation is lethal, but heterozygote mutants showed many symptoms of papillorenal syndrome, including optic nerve dysplasia with abnormal vessels emerging from the periphery of the optic cup and small dysplastic kidneys. It is shown that Pax2 is under upstream control of Shh in both mice and zebrafish, which is expressed in the precordial plate.^[2]

PAX2 gene mutation is expressed in the development of Kidneys, Otic, optic cup and, midbrain–hindbrain boundary. For pathogenesis, The PAX2 mutations have believed to cause the loss of function of one allele known as haploinsufficiency. This PAX2 haploinsufficiency is mostly seen in the conditions associated with the ocular, urogenital, and other abnormalities in humans. Some of the patients with Renal coloboma syndrome also reported having missense mutations.

The exact mechanism by which this causes the disease is still not explained. Scientists have explored the association between this mouse mutation with the paired domain mutation usually seen in humans, The science has tried to explain the expression of mutant proteins in vitro as well as in vivo at a slow pace and lower level as compared to with wild type protein.

The patients with missense mutations in PAX2^[5] will develop Papillorenal syndrome due to the hypomorphic nature of the alleles and the residual function of these couldn’t suppress the development of the ocular and renal disease.

Genetics

Renal coloboma syndrome or papillorenal syndrome is an autosomal dominant disorder that mainly results due to the mutation in the PAX2 gene. This mutation is located on the chromosome 10q24.3-q25.1.Pa­pil­lore­nal syn­drome is an au­to­so­mal dom­i­nant dis­or­der that re­sults from a mu­ta­tion of one copy of the Pax2 gene, lo­cated on chro­mo­some 10q24.3-q25.1.

The gene is related to the de­vel­op­ment of eyes and the kid­neys

Au­to­so­mal dom­i­nant in­her­i­tance- The gene for the papillorenal syndrome is located on an autosome and the one mutated copy of the gene is good enough to cause the renal coloboma syndrome when inherited from the parent to offspring.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

The renal coloboma syndrome differentials include most of the disease with renal and ocular anomalies. The numerous important differentials are CHARGE Syndrome that includes characteristic five features of the disease including Coloboma, Heart Abnormalities, Choanal Atresia, Growth and development Retardation, Genital Anomalies, Ear and hearing abnormalities. A lot of patients studied under renal coloboma syndrome do not have any sort of craniofacial anomalies that are typical of CHARGE Syndrome. Other differentials include Branchio-oto-renal syndrome – Renal hypoplasia in these patients makes this an important differential. Pt with PAX6 Mutations – significant overlap with eye findings in patients with PAX6 gene mutation make it an important differential but the renal anomalies that are typical for RCS are absent in these patients. COACH Syndrome or Joubert – Important differential due to the presence of both renal abnormalities and coloboma in these patients. However, patients with Renal coloboma syndrome does not have any developmental abnormality, cerebellar abnormalities, and/or hepatic dysfunction. Cat Eye Syndrome – This genetic abnormality is having symptomatic overlap with renal coloboma syndrome but the Iris coloboma that is typical for RCS is usually not observed in this disorder.

Various differential diagnosis of renal coloboma syndrome are as follows^[1][2]:

• CHARGE syndrome^[3]
  • Coloboma
  • Heart Abnormalities
  • Choanal Atresia
  • Growth and development Retardation
  • Genital Anomalies
  • Ear and hearing abnormalities

A lot of patients studied under renal coloboma syndrome do not have any sort of craniofacial anomalies that are typical of CHARGE Syndrome.

• Branchio-oto-renal syndrome– Renal hypoplasia in these patients makes this an important differential.

• PAX6 Mutations – significant overlap with eye findings in patients with PAX6 gene mutation make it an important differential
  • The renal anomalies that are typical for RCS are not present in these patients.

• COACH Syndrome or Joubert^{[4] [5]}– Important differential due to the presence of both renal abnormalities and coloboma in these patients.
  • However, patients with Renal coloboma syndrome does not have any characteristic features of Joubert syndrome that is:
    • Developmental abnormality
    • Cerebellar abnormalities

      

    • Hepatic dysfunction
  • Important symptoms of this syndrome include:
    • Abnormally large head and forehead
    • Renal Cyst
    • Jerky Eye movements
    • Developmental delays
    • Hypotonia with unsteadiness

• Cat Eye Syndrome – This genetic abnormality is having symptoms overlapping with renal coloboma syndrome
  • The Iris colobomas that are typical for RCS are usually not observed in this disorder.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

The Prevalence of the disease and the prevalence at birth is still unknown. In a study conducted in 90 families, they found 177 mutation-positive cases. The number of individuals with mutation-negative is not known in that study. The conclusion derived showed no ethnic predilection for the disease. The major component found in the causation of RCS is PAX2 gene (10q24) in half of the patients with renal and optic nerve abnormalities.

• The Prevalence^[1] of the disease and the prevalence at birth is still unknown.
• In a study conducted in 90 families, they found 177 mutation-positive cases. The number of individuals with mutation-negative is not known in that [study]]. The conclusion derived showed no ethnic predilection for the disease.
• The major component found in the causation of RCS is the PAX2 gene (10q24) in half of the patients with renal and optic nerve abnormalities.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

The pathophysiology and the risk factors responsible for the development of Renal-coloboma syndrome is mainly genetic and related to the expression of PAX 2 gene. So the genetic inheritance is the main risk factor or the important determinant in the causation of Renal-coloboma syndrome. This genetic syndrome keeps on clustering in the future generations.

The environmental risk factors that impact the pregnancy like alcohol and some drugs may also contribute to the development of Renal-coloboma syndrome. In conclusion, RCS leads to the abnormal development of organs like kidney and eyes during the pregnancy period. The abnormal development of eyes usually happens in the third trimester during that time the eyes are formed. The abnormalities usually occur due to the impairment in the closure of the optic disc. It usually depends on which specific part or areas of optic fissure fails to close.

The pathophysiology and the risk factors responsible for the development of Renal-coloboma syndrome is mainly genetic and related to the expression of PAX2^[1][2] gene. So the genetic inheritance is the main risk factor and this genetic syndrome keeps on clustering in the future generations. The environmental risk factors that impact the pregnancy like alcohol and some drugs may contribute to the development of Renal-coloboma syndrome. In conclusion, RCS leads to the abnormal development of organs like kidney and eyes during the pregnancy period. The abnormal development of eyes usually happens in the third trimester during that time the eyes are formed. The abnormalities usually happen when there is a failure of optic disc closure. It usually depends on which specific part or areas of optic fissure fails to close.

Coloboma^[3] or keyhole pupil might occurs all of sudden at its own during the pregnancy or it may be acquired. Some cases reported that even isolated coloboma is passed from one generation to another.

Prenatal care and diagnostic evaluation are possible for the cases where there is a high index of suspicion or if there is a clear cut family history of PAX2 gene mutation running in the family. This Renal-coloboma syndrome usually presents in autosomal dominant pattern with variations and complications due to other associated genetic manipulations like variable expression, genetic mosaicism and/or incomplete penetrance.

The eyes in the fetus develop during the first 3 months. Choroidal fissure forms the eye. This usually closes by the seventh week of pregnancy and failure of closure of this results in the development of coloboma. Usually affects one eye but at point seen affecting both eyes as well. There are different types of coloboma based on the structural and functional tissue of the eye affected.

Lens coloboma– The missing part is the lens piece

Eyelid coloboma– The missing tissue here is part of the upper or lower eyelids.

Optic nerve coloboma– Optic nerve is affected that results in the impairment of vision.

Uveal coloboma– If the coloboma affects the iris then it is given a special name called Cat-eye appearance.

Chorio-retinal coloboma– Retina is the missing part in this case.

Macular coloboma– The development of macula is abnormal in this case.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

RCS is an autosomal dominant disorder characterized by renal and ocular anomalies. It is mainly relate to the PAX2 gene mutations. Epidemiological estimated incidence of coloboma is about 1 in 10,000 births. Only the coloboma itself is estimated to account for 3-11% of blindness in children’s worldwide. Prevalence of disease is still unknown with more than 60 cases are reported in the scientific literature. The most common complications associated are: End stage renal disease, VUR (Vesicoureteral reflux), Eyelidcoloboma, Iris coloboma. The prognosis for renal coloboma syndrome depends primarily on the treatment the patient is receiving. The prognosis for renal coloboma syndrome is worse in the presence of congenital anomalies in the patient.

RCS is an autosomal dominant disorder characterized by renal and ocular anomalies. It is mainly relate to the PAX2^[1] gene mutations. Epidemiological estimated incidence of coloboma is about 1 in 10,000 births. Only the coloboma itself is estimated to account for 3-11% of blindness in children’s worldwide. Prevalence of disease is still unknown with more than 60 cases are reported in the scientific literature. Patients with this disorder typically has small underdeveloped or hypoplastic kidneys leading in most of the cases into ESRD^[2]. Additionally in the eyes the malformation of optic nerve leads to the development of colobomas, which are mainly referred to as hole in the eye tissue.

There are numerous complications associated with patients of renal coloboma syndrome mainly involving renal and ocular manifestations.

The most common complications associated are:

End stage renal disease

VUR (Vesicoureteral reflux)

Eyelid coloboma^[3]

Iris coloboma

• Photophobia.
• Presence of double vision or blurring in the eyes.

Choroidoretinal coloboma

• Amblyopia
• Anisometropia,
• Retinal detachment ( Most common complication seen in patients with Choroidoretinal and optic disc coloboma)
• Strabismus
• Lens subluxation
• Cataracts
• Lens subluxation (uncommon).
• Glaucoma
• Morning glory disc anomaly
  

The prognosis for Renal-coloboma syndrome depends primarily on the adequacy and accuracy of treatment the patient is receiving.

Renal failure or ESRD can occur at any age

• Treatment modalities used are dialysis and renal transplantation.

The prognosis for RCS is worse in the presence of congenital anomalies in the patient^[4].

• If concomitant congenital heart disease ( cyanotic), anomalies with the brain and spinal cord, and esophageal atresia
• The prognosis is bad/unfavorable

Formal longitudinal studies of visual prognosis have not been carried out^[5].

Ocular prognosis or prognosis for the vision mainly depends on:

• The severity

• The Location of colobomas in the eye ( in relation to the optic nerve and maculopapular bundle and macula)

• The Presence of complications like
  • Amblyopia
  • Retinal detachment.

The prognosis in patients with morning glory syndrome is usually poor^[6].

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