Clinical Guidance

Review of all reported cases to date does not reveal a consistent genotype/phenotype correlation. This is most dramatically illustrated by the tremendous intrafamilial variability in the severity of ocular and renal findings. To date, no clear evidence suggests that the location of a pathogenic variant (paired domain, octapeptide domain, partial homeodomain, or transactivation domain) or the type of pathogenic variant (missense variant, nonsense variant, or gene deletion) consistently predicts the clinical phenotype.

Source: GeneReviews — "PAX2-Related Disorder"

Penetrance

Only one individual with a pathogenic variant in PAX2 in whom renal and ophthalmologic examinations were performed and documented as normal has been reported . Thus, penetrance appears to be greater than 99%. In individuals with pathogenic variants in PAX2, the penetrance of eye malformations is at least 77% . This should be viewed as a minimum figure, as fully 21% of individuals with PAX2 pathogenic variants have not had a dilated eye examination to evaluate for subclinical abnormalities of the optic nerve. The penetrance for renal malformations or renal disease is at least 92%. Again, this figure should be viewed as a minimum, as some individuals with pathogenic variants have not had full renal evaluations.

Source: GeneReviews — "PAX2-Related Disorder"

Diagnostic Criteria

Renal coloboma syndrome (or papillorenal syndrome) was the name given to an autosomal dominant condition associated with renal hypodysplasia and abnormalities of the optic nerve and a heterozygous pathogenic variant in PAX2. With improved access to molecular genetic testing, more individuals have been identified and it has become clear that multiple phenotypes beyond that of classic renal coloboma syndrome may be associated with pathogenic variants in PAX2. The authors feel that the term "PAX2-related disorder" best reflects this wide phenotypic variability. There are no formal diagnostic criteria for PAX2-related disorder.

Suggestive Findings

PAX2-related disorder should be suspected in individuals with the following clinical findings in the and/or . Note: PAX2 pathogenic variants are more ...

Source: GeneReviews — "PAX2-Related Disorder"

Differential Diagnosis

Table 2. Disorders to Consider in the Differential Diagnosis of PAX2-Related Disorder

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PAX2-related disorder, the following are recommended if they have not already been completed:

• Evaluation of renal structure by renal ultrasound examination

• Measurement of renal function by serum electrolyte concentrations, BUN, and creatinine

• Urinalysis to evaluate for the presence of blood and protein

• Evaluation for vesicoureteral reflux, by voiding cystourethrogram (VCUG)

• Dilated eye examination

• Audiologic assessment (See Genetic Hearing Loss Overview for details of audiologic assessment.)

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

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.

Prevention of Secondary Complications

Prevention of retinal detachment in those with congenital optic nerve abnormalities includes close follow up with an ophthalmologist and use of protective eyewear.

Surveillance

No disease-specific guidelines hav...

Source: GeneReviews — "PAX2-Related Disorder"

Clinical Guidance

Avoid the following:

• Use of medications known to affect renal function (requires consultation with a specialist in nephrology)

• Contact sports

Source: GeneReviews — "PAX2-Related Disorder"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "PAX2-Related Disorder"

Surveillance Guidelines

No disease-specific guidelines have been developed. The following ongoing evaluations are recommended in all individuals with PAX2-related disorder.

• Follow up by a nephrologist to monitor renal function and blood pressure

• Follow up by an ophthalmologist to monitor vision. Any change in vision could indicate a retinal detachment and should be treated as a medical emergency.

• Audiometric evaluation with periodic follow up

Source: GeneReviews — "PAX2-Related Disorder"