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Why has this 72-year-old woman with a history of kidney disease developed visual changes that affect only her left eye?

When the patient presented for an eye exam, M. Tariq Bhatti, MD, and colleagues at Kaiser Permanente-Northern California in Roseville, learned that she had been living with kidney disease for much of her life. By the age of 50, she had developed end-stage renal disease and received a kidney transplant. This was followed by a second kidney transplant 15 years later, they reported in .

They pointed out that the patient's medical records could not be obtained from the hospital that had provided treatment at the time. The patient could not remember if she had received any precise diagnosis, but she reported having proteinuria since she was age 7.

She also had high cholesterol, arterial hypertension, and a lung infection caused by Mycobacterium avium complex. The patient's family history offered no additional relevant information; she noted having two healthy adult children.

The patient told clinicians that her first eyesight problem had developed a year after she received the first kidney transplant. At that time, she noted an inferior visual field defect affecting her left eye, which was diagnosed as nonarteritic anterior ischemic optic neuropathy. Several years after that diagnosis, she underwent uncomplicated bilateral cataract procedures.

On presentation, clinicians performed an eye examination that revealed a visual acuity with distance correction of 20/25 for the right eye and 20/30 for the left eye. External and slit-lamp examinations revealed bilateral pseudophakia.

Other findings included:

• Color vision: 14/14 plates, each eye
• Left relative afferent pupillary defect
• Confrontation visual field: full for right eye and inferior defect for the left eye

Anomalies were noted in both optic discs: the right optic disc was dysplastic, with a subtle appearance of the peripherally located blood vessels emanating from the central disc. The left eye showed greater central excavation than the right eye, with peripherally located blood vessels and the absence of central vessels. The rest of the posterior pole and retinal vessels appeared normal in both eyes.

Based on the appearance of the patient's optic discs (especially her left eye), Bhatti and team arrived at a clinical diagnosis of vacant optic disc associated with autosomal dominant papillorenal syndrome (PAPRS). Genetic testing was performed.

Regarding other diagnostic options, the team said that cranial MRI was not necessary since the patient did not have a morning glory disc anomaly (MGDA) that might be associated with a basal encephalocele or moyamoya disease.

Blood tests were not needed, since the symptoms were unlikely to be due to an underlying vasculitic condition, they noted, and a PET scan was unnecessary since a vacant optic disc is not associated with an underlying malignancy.

The diagnosis was confirmed by findings of sequence analysis, which revealed a heterogeneous pathological variant (c.335G>A) in the .

Bhatti and colleagues referred the patient for genetic counseling, to help explain the implications of the PAX2 gene variant and the 50% risk that her children may also carry this genetic variant.

Discussion

PAPRS -- also referred to as renal-coloboma syndrome, and optic coloboma vesicoureteral reflux-renal anomalies, among other terms -- was . Its clinical characteristics were described in greater detail about two decades later. In 1995, PAPRS was determined to be of the PAX2 gene.

Because it was caused by a variety of different gene mutations, experts have suggested that PAPRS be termed PAX2-related disorders, Bhatti and team wrote. "However, have a known PAX2 variant."

Clinically, the syndrome presents with abnormalities affecting the kidneys, and one or both eyes. Optic disc abnormalities are reported in about 70% of patients, and about one in 10 have retinal anomalies. "A forme fruste of the disease may present with only one of these conditions," the authors noted.

End-stage kidney disease due to renal dysfunction can affect patients of any age, and causes a variety of pathologies, including:

• Kidney hypoplasia or dysplasia
• Multicystic dysplastic kidney
• Oligomeganephronia
• Vesicoureteral reflux
• Focal segmental glomerulosclerosis
• Uric acid nephrolithiasis

"Systemic manifestations include hearing loss, growth retardation, microcephaly, developmental delay, gout, joint laxity, and soft skin," Bhatti and colleagues wrote. "The hallmark eye finding is an anomalous optic disc, which was initially termed a coloboma."

However, they suggested that based on its clinical characteristics and suggested embryogenesis, vacant optic disc describes the syndrome more closely.

Some patients with PAPRS may also develop retinal coloboma, scleral staphyloma, optic nerve cyst, foveal hypoplasia, macular changes, and microphthalmia. "Excavated or cavitary optic disc anomalies comprise a group of congenital, morphologically distinct conditions, which include vacant optic disc, MGDA, optic disc coloboma, megalopapilla, optic disc pit, and peripapillary staphyloma," they explained.

These anomalies have been suggested to represent a spectrum "because certain optic discs do not conform to any one particular entity," they added. The PAX2 gene is one of a family that includes eight other PAX genes. Located on chromosome 10, the PAX2 gene encodes a transcriptional factor that is integral to eye, kidney, and central nervous system development.

Bhatti's group referred to a theoretical etiology proposed in 2001 suggesting that "the vacant optic disc arises from deficiency in vascular development during embryogenesis, resulting in the absence of central retinal vessels within the excavated optic disc, with the peripheral vasculature representing cilioretinal vessels." In contrast, an optic disc coloboma is marked by "an absence of tissue in the inferonasal quadrant of the disc and the central retinal vessels emerge superotemporally from the unaffected portion of the disc."

The team emphasized the importance of "recognizing a vacant optic disc and differentiating it from MGDA and optic disc coloboma" to facilitate timely identification and treatment of .

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