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NPHP1-Associated Retinal Degeneration

Home / Retina and Vitreous Retinal Degenerations Associated with Systemic Disease

Title: NPHP1-Associated Retinal Degeneration
Author (s): Sam Wilkinson, MD, Cecinio Ronquillo, MD, PhD
Date: 08/05/2020
Keywords/Main Subjects: NPHP1, Senior-Løken Syndrome, Retinitis pigmentosa

Diagnosis: NPHP1-associated retinal degeneration (Senior-Løken Syndrome)

Description of Case: A 35-year-old female presented with worsening vision loss in both eyes. Her past medical history includes end-stage renal disease status post kidney transplant secondary to medullary cystic kidney disease, migraine with aura, and hypertension.

Her ophthalmic examination was remarkable for best corrected visual acuity of OD: 20/30 and OS: 20/40. Her visual fields were severely constricted, bilaterally. Ishihara test resulted in OD: 8/11 and OS: 6/11. Her pupils, external, and motility examinations were within normal limits. A funduscopic examination was remarkable for OU 3+ disc pallor, RPE changes, vascular attenuation, bone spicule pigment changes, and cobblestone degeneration (Figure 1).

Fundus autofluorescence imaging (Figure 2) showed a ring of hyperautofluorescence around the macula. Goldmann visual field testing showed severely constricted visual fields (Figure 3).

The patient’s examination, image findings, and kidney disease were consistent with Senior-Løken Syndrome.

Epidemiology: Senior-Løken Syndrome is a rare condition affecting approximately 1 in 1 million people globally.

Genetics: Senior-Løken Syndrome is an autosomal recessive disease. Mutations of several genes called nephrocystins can cause Senior-Løken Syndrome, including NPHP1, Inversin/NPHP2, NPHP3, NPHP4, IQCB1/NPHP5, CEP290/NPHP6, GLIS2/NPHP7, RPGRIP1L/NPHP8, NEK8/NPHP9, SDCAAG8/NPHP10, TMEM67/NPHP11, TTC21B/NPHP12, and WDR19/NPHP13. Nephrocystins are proteins found in cilium of photoreceptor cells as well as in cilium of renal cells. Defective connective cilium are thought to impair cell signaling, which leads to the retinal and renal dysfunction. NPHP1 mutations comprise 21% of all nephronophthisis cases. Retinal dystrophy occurs in less than 40% of patients with a mutation in NPHP1-4 and 100% of the patients with NPHP5 and NPHP6.

The specific role of nephrocystin-1 is unknown but is thought to be important for the normal function of cilia in the retina, kidney, and respiratory tract.

Clinical Exam: Mutations in NPHP1 can cause RP. Like other mutations causing Senior-Løken Syndrome, patients harboring mutations in NPHP1 also have nephronophthisis, which causes cortico-medullary cysts in the kidneys ultimately leading to kidney failure. Other findings for NPHP1 mutations include oculomotor apraxia, hyperpnea, hypotonia, mental retardation, and ataxia.

Diagnosis/Testing: Diagnosis is based on the clinical picture of renal impairment and retinal degeneration. Clinical suspicion should lead to genetic testing. Referral to a nephrologist is warranted; however, renal symptoms typically precede eye problems. A renal ultrasound will show cortico-medullary cysts.

Clinical Course: Patients typically present with nyctalopia and experience progressive visual impairment. Patients also progress to end-stage renal disease (ESRD) requiring renal transplantation.

Management: There are no treatments available that halt or reverse disease progression. Management is primarily supportive treatment, especially regarding renal complications. Supportive treatments include adequate hydration, erythropoietin and iron for patients with anemia, and vitamin D supplementation and phosphate binders for patients with secondary hyperparathyroidism. Renal transplantation is an effective treatment for ESRD; tubular injury typically does not recur.

Images or video:

OD

Wilkinson-Ronquillo-NPHP1-Figure-1.1

OS

Wilkinson-Ronquillo-NPHP1-Figure-1.2

Figure 1. Montage photos showing optic nerve pallor, vascular attenuation and significant bone spicules in both eyes.

 

OD

Wilkinson-Ronquillo-NPHP1-Figure-2.1

OS

Wilkinson-Ronquillo-NPHP1-Figure-2.2

Figure 2. Fundus autofluorescence showing a ring of hyperreflectivity around the macula and peripheral hypofluorescent spots.

 

OD

Wilkinson-Ronquillo-NPHP1-Figure-3.1

 

OS

Wilkinson-Ronquillo-NPHP1-Figure-3.2

Figure 3. Goldmann visual perimetry showing severely diminished visual fields.

 

Summary of the Case:

Format: Image

References:

Faculty Approval by: Cecinio Ronquillo, MD, PhD and Paul S. Bernstein, MD, PhD

Copyright statement: Copyright Sam Wilkinson, MD, Cecinio Ronquillo, MD, PhD, ©2021. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/

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