Renal coloboma syndrome

Other Names: Papillorenal syndrome; Optic nerve coloboma with renal disease; Optic coloboma, vesicoureteral reflux, and renal anomalies; Coloboma of optic nerve with renal disease

Renal coloboma syndrome (also known as papillorenal syndrome) is a condition that primarily affects kidney (renal) and eye development.

Epidemiology

The prevalence of renal coloboma syndrome is unknown; at least 60 cases have been reported in the scientific literature.

Cause

Renal coloboma syndrome is caused by mutations in the PAX2 gene. The PAX2 gene provides instructions for making a protein that is involved in the early development of the eyes, ears, brain and spinal cord (central nervous system), kidneys, and genital tract. The PAX2 protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the PAX2 protein is called a transcription factor. After birth, the PAX2 protein is thought to protect against cell death during periods of cellular stress.

Mutations in the PAX2 gene lead to the production of a nonfunctional PAX2 protein that is unable to aid in development, causing incomplete formation of certain tissues. Why the kidneys and eyes are specifically affected by PAX2 gene mutations is unclear. Approximately half of those affected with renal coloboma syndrome do not have an identified mutation in the PAX2 gene. In these cases, the cause of the disorder is unknown.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

People with this condition typically have kidneys that are small and underdeveloped (hypoplastic), which can lead to end-stage renal disease (ESRD). This serious disease occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. It has been estimated that approximately ten percent of children with hypoplastic kidneys may have renal coloboma syndrome. The kidney problems can affect one or both kidneys.

Additionally, people with renal coloboma syndrome may have a malformation in the optic nerve, a structure that carries information from the eye to the brain. Optic nerve malformations are sometimes associated with a gap or hole (coloboma) in the light-sensitive tissue at the back of the eye (the retina). The vision problems caused by these abnormalities can vary depending on the size and location of the malformation. Some people have no visual problems, while others may have severely impaired vision.

Less common features of renal coloboma syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing loss.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Optic nerve dysplasia
• Renal insufficiency(Renal failure)

30%-79% of people have these symptoms

• Multicystic kidney dysplasia
• Myopia(Close sighted)
• Renal dysplasia
• Renal hypoplasia(Small kidneys)
• Stage 5 chronic kidney disease
• Vesicoureteral reflux
• Visual impairment(Impaired vision)

5%-29% of people have these symptoms

• Cataract(Clouding of the lens of the eye)
• Edema(Fluid retention)
• Hearing impairment(Deafness)
• Horseshoe kidney(Horseshoe kidneys)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Lens luxation(Dislocated lens)
• Macular degeneration
• Macular hyperpigmentation
• Nephrolithiasis(Kidney stones)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Optic nerve coloboma
• Renal malrotation(Abnormal rotation of the kidneys)
• Retinal coloboma(Hole in the back of the eye)
• Retinal detachment(Detached retina)
• Strabismus(Cross-eyed)

Diagnosis

The diagnosis of PAX2-related disorder is established in a proband with the characteristic renal and/or eye findings by the identification of a heterozygous pathogenic variant in PAX2 by molecular genetic testing. Among individuals with apparently nonsyndromic renal hypodysplasia and in families with autosomal dominant isolated focal segmental glomerulosclerosis, pathogenic variants in PAX2 have been identified in approximately 8% and 4%, respectively.

Treatment

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

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

NIH genetic and rare disease info

• NIH info on Renal coloboma syndrome

Renal coloboma syndrome is a rare disease.

Renal coloboma syndrome Resources
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