Case report: A case of Norrie disease due to deletion of the entire coding region of NDPgene



Norrie disease is a rare X-linked recessive vitreoretinopathy. Variants of the NDP gene are associated with this condition. This case reports aims to demonstrate the variations of clinical presentations and exam findings of this disease.


A retrospective chart review of the patient’s ocular and systemic findings and imaging results was performed. The patient had received genetic testing, including mutational analysis of targeted genes associated with retrolental masses. The patient had a comprehensive eye exam for bilateral leukocoria, demonstrating large retrolental masses, anterior polar cataracts, stretched ciliary processes, and roving eye movements. B-scan ultrasonography and magnetic resonance imaging indicated total, funnel-shaped retinal detachments, which is a unique retinal configuration in Norrie disease. Genetic testing confirmed deletion of the coding region of all three exons in the NDP gene, which confirmed Norrie disease. He has not shown any extraocular involvement to date.

Conclusions and Importance

This is a case demonstrating the association between deletion of the coding region NDP gene and Norrie disease. The phenotypical variation of this disease warrants further studies of genotype-phenotype correlations and mutations of the NDP gene.


Norrie disease is a rare X-linked recessive disorder that is characterized by a varying degree of fibrovascular changes within the eyes. Encoded by the “Norrie disease (pseudoglioma)” ( NDP ) gene (MIM: 300658 ; cytogenetic location: Xp11.3), Norrin is a protein that is thought to be important in retinal neuroprotection and retinal angiogenesis. , Pathogenic variants of NDP are associated with Norrie disease and related vitreoretinopathies of milder phenotypes. To date, more than 100 mutations of NDP have been identified — which include missense, null, splice, and deletions — leading to an abnormal gene product. Patients with Norrie disease may have congenital blindness associated with abnormal findings such as leukocoria, iris atrophy, corneal opacity, cataract, and retinal dysgenesis with an associated fibrovascular mass (a.k.a. pseudoglioma). , Secondary tractional retinal detachment is very common at birth, and thus, there is a high risk of developing phthisis bulbi with age. In addition, there may be extraocular manifestations such as sensorineural hearing loss and mental cognitive and behavioral impairments. Herein, we present a case of Norrie disease due to a deletion of the coding region of NDP gene and the associated clinical findings, including some unique retinal configurations.

Case report

Clinical findings

A 7-week-old, African-American male was referred to our institution for bilateral leukocoria. His mother and primary care provider noted normal red reflexes until 5 weeks of age. His family history was significant for a paternal great uncle who had unilateral blindness causing strabismus at 3 years old and his paternal grandfather who had high myopia. On exam, the patient had roving eye movements and did not blink or wince to light in either eye. The anterior chamber of both eyes appeared quiet but shallow. The anterior segment was otherwise notable for an anterior polar cataract with fine persistent pupillary membrane and peripheral maldevelopment of the anterior leaflet of the iris. A large, white retrolental mass could be seen in each eye, which had an irregular surface but no prominent vascular dilatation or tortuosity. The mass appeared to be stretching the ciliary processes, particularly in the right eye ( Fig. 1 A and B). B-scan of each eye demonstrated a funnel shaped retinal detachment but no hyperechoic spots within the intraocular mass that would be consistent with calcifications ( Fig. 1 C and D). Magnetic resonance imaging (MRI) of the brain and orbits ( Fig. 2 A) showed heterogeneous masses in each globe and retinal detachment with mild microphthalmia. The optic nerves were hypoplastic with markedly diminutive prechiasmatic size and a barely discernible optic chiasm. In addition, bilateral enhancement of the intraorbital optic nerves, oculomotor nerves, and trigeminal nerves was noted — albeit partially visualized in the case of cranial nerves III ( Fig. 2 B) and V ( Fig. 2 C). The patient was followed with serial exams and B-scans to ensure there was no calcification formation, and a normal RB1 analysis helped rule out retinoblastoma. Cranial nerve enhancement raised the possibility of an infectious or inflammatory condition. TORCH titers, including for lymphocytic choriomeningitis virus (LCMV), were unremarkable. Lumbar puncture, complete blood count, and complete metabolic panel were also unremarkable. At the age of 3 months, his right eye had a funnel-shaped retinal detachment; his left eye showed central hyperechoic area with globe disorganization, posterior synechiae, retinal detachment in the periphery, and probable funnel detachment. Subsequently, he had vitrectomy of both eyes after which he was able to track light with both eyes. At surgery, the retinal detachment was directly viewed, confirming the funnel shape ( Fig. 3 ). Genetic analysis ultimately revealed complete deletion of the NDP gene, confirming the diagnosis of Norrie disease. He underwent additional vitrectomy, membranectomy, and retinal repair of the right eye. The structural outcome resulted in an open funnel-shaped retinal detachment. His most recent visit at the age of 3.5 years old indicated no measurable vision in either eye, and his left eye was phthisical.

Fig. 1

External color photographs and B-scans.

A–B: External color photographs of the right (A) and left (B) eyes highlight the large, white retrolental mass in each eye with stretched ciliary processes (right > left eye) and anterior iris atrophy (left > right eye).

C–D: B-scan ultrasonography of right (C) and left (D) eyes show a retrolental mass taking up the majority of the posterior segment and absent of discrete hyperechoic spots that would indicate calcifications. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Magnetic resonance imaging of the brain and orbits

A: Axial T1-weighted image showing heterogeneous masses in both eyes, funnel-shaped retinal detachment in the left eye, and mild microphthalmia of both eyes

B–C: Axial fat saturated, T2-weighted image highlighting bilateral enhancement of cranial nerves III (arrows in B) and V (arrows in C).

Jan 3, 2022 | Posted by in OPHTHALMOLOGY | Comments Off on Case report: A case of Norrie disease due to deletion of the entire coding region of NDPgene

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