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A. B. Daniels, C. Westerfeld, C. M. Andreoli, S. Mukai; Initially Misdiagnosed Norrie Disease Diagnosed by NDP Sequencing. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5241.
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Norrie disease (ND) is a rare X-linked recessive primary retinal vasculopathy leading to total retinal detachment (RD) and retinal dysplasia. It is frequently misdiagnosed clinically as retinoblastoma (RB) or RD not from ND. Prompt genetic diagnosis is possible by sequencing the Norrie gene (NDP). We evaluated the clinical and genetic features of ND.
We performed a retrospective chart review of all consecutive cases of ND seen in the Retina Service at Massachusetts Eye and Ear Infirmary from 1996-2008. All cases were confirmed by identification of a matching mutation in the NDP gene in the male patient and the mother.
Three boys with ND were identified. In all cases, leukocoria was noted by age 1 month. Two cases were referred for advanced bilateral RB. First case had positive family history of RB (father’s cousin) and was referred for enucleation. Second case had been treated by 6 cycles of systemic chemotherapy with no response and was referred for radiotherapy. Third case was referred for surgical management of RD after attempted repair by pars plana vitrectomy in the other eye led to phthisis. In all cases, there was a dense whitish plaque adherent to the posterior lens. One case had significant vitreous hemorrhage bilaterally. Direct sequencing of the NDP gene detected matching null mutations in the child and the mother. The three mutations were stop codon in exon 3, complete deletion of NDP, and nonsense mutation in exon 2. No additional procedures were recommended for the eyes.
NDP is a small gene that can be sequenced relatively quickly. In cases where ND is a significant part of the differential diagnosis, direct sequencing of NDP for null mutations is extremely useful. Even in cases of RB, a delay of days for NDP testing will not compromise management. The correct diagnosis can avoid high risk procedures such as systemic chemotherapy, radiotherapy, enucleation, and RD surgery. Avoidance of carboplatin, a chemotherapeutic agent commonly used in RB therapy, is especially important since it carries a risk of hearing loss; this is of special concern since, in addition to blindness, ND causes hearing loss in approximately 30% of cases.
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