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Case of Coats disease associated with neurofibromatosis type 1

Published:September 28, 2020DOI:https://doi.org/10.1016/j.jcjo.2020.09.005
      A 24-month-old boy with neurofibromatosis type 1 (NF1) was found to have Coats disease during clinical follow-up examination. The relationship between the 2 conditions is discussed.
      A newborn was diagnosed with NF1 after birth based on clinical criteria
      • Ferner R.E.
      • Huson S.M.
      • Thomas N.
      • et al.
      Guidelines for the diagnosis and management of individuals with neurofibromatosis 1.
      : his mother was diagnosed with NF1, and he had more than 6 café au lait spots. The patient's mother did not have any ocular history. When the boy was 3 months old, we performed a complete ophthalmic examination for optic nerve glioma screening. Findings of the anterior segment examination and funduscopic examination were unremarkable, especially optic nerve head edema was not detected, and he was asked to come back at age of 9 months to conduct the refractive screening (Supplementary Fig. 1, available online). The patient was lost to follow-up. He was referred to our department at the age of 17 months for leukocoria in his right eye. Findings of his neurologic examination were normal. He was uncomfortable when his left eye was covered. Cycloplegic refraction performed under cyclopentolate 1% was within normal range. Anterior segment examination showed clear cornea and normal crystalline lens, and no Lisch nodules were seen.
      Funduscopic examination revealed peripheral retinal telangiectasia associated with diffuse intraretinal exudation, which was consistent with stage 2b Coats disease according to Shields et al. Classification
      • Shields J.A.
      • Shields C.L.
      • Honavar S.G.
      • Demirci H.
      • Cater J.
      Classification and management of Coats disease: the 2000 Proctor Lecture.
      (Fig. 1A). He subsequently underwent peripheral laser photocoagulation under general anaesthesia. Intraocular pressure was normal.
      Fig 1
      Fig. 1Funduscopic examination at 17 months of age showed peripheral telangiectasia with diffuse intraretinal exudation (A), which was treated by laser photocoagulation. Intraoperative optical coherence tomography demonstrated intra- and subretinal exudates (B).
      Intraoperative spectral-domain optical coherence tomography images were obtained using the Retcan 700 (Carl Zeiss Lumera 700 with integrative HD OCT, Carl Zeiss Meditec AG) and demonstrated marked intraretinal and subretinal exudation in the macular area (Fig. 1B). After 1 month, a second peripheral laser photocoagulation session was required for persistent active telangiectasia. Follow-up examination at 1 month disclosed regression of the peripheral telangiectasia and development of foveolar nodule (Supplementary Fig. 2, available online). The child did not require further laser photocoagulation during the 7 months’ follow-up.
      NF1 is an inherited autosomal dominant disease caused by mutation of the NF1 gene on chromosome 17, which encodes the protein neurofibromin. However, the diagnosis is based on clinical criteria, and mutational screening is not required for the diagnosis. The main objective of the ophthalmic examination in children with NF1 is early detection of optic nerve glioma. Other common ophthalmic signs include Lisch nodule and choroidal schwannoma, which are asymptomatic. Parrozzani et al. found that 6.1% of patients
      • Parrozzani R.
      • Pilotto E.
      • Clementi M.
      • Frizziero L.
      • Leonardi F.
      • Convento E.
      • et al.
      Retinal vascular abnormalities in a large cohort of patients affected by neurofibromatosis type 1.
      with NF1 had retinal vascular abnormalities called corkscrew vessels defined as well-defined, small, tortuous retinal vessels with a spiral aspect, originating from small tributaries of retinal veins, localized by optical coherence tomography angiography in the superficial vascular plexus. Shields et al. reported 6 patients with NF1 and retinal vasoproliferative tumours
      • Shields J.A.
      • Pellegrini M.
      • Kaliki S.
      • Mashayekhi A.
      • Shields C.L.
      Retinal vasoproliferative tumors in 6 patients with neurofibromatosis type 1.
      and hypothesized that there is retinal ischemia, retinal vascular proliferation, and glial proliferation leading to retinal vasoproliferative tumours. It has been shown experimentally that neurofibromin deficiency induced endothelial cell proliferation and retinal neovascularization.
      • Zhang H.
      • Hudson F.Z.
      • Xu Z.
      • et al.
      Neurofibromin deficiency induces endothelial cell proliferation and retinal neovascularization.
      However, we found only one previous report on the association between NF1 and Coats disease. We hypothesize that the loss of neurofibromin function leads to retinal vascular abnormalities associated with NF1 that result in localized retinal ischemia with vascular proliferation and exudation leading to Coats disease.
      Coats disease is much rarer than NF1, with an estimated prevalence of 0.09/100 000 children. It is a congenital disease but not hereditary; the ratio of boys to girls is 3:1. Characteristic features include peripheral telangiectasia, intraretinal exudation, and retinal detachment. The Norrie disease gene has been suggested as the causal gene in Coats disease.
      To the best of our knowledge, the association between NF1 and Coats disease has been described only once in the literature.
      • Chiu S.L.
      • Chen S.N.
      • Chen Y.T.
      • Chen P.J.
      Coats’ disease and neovascular glaucoma in a child with neurofibromatosis.
      There is no clue for a common genetic origin because the NF1 is much more prevalent than Coats disease.
      There are several articles describing retinal vascular abnormalities associated with NF1. Our report suggests that NF1 may be a risk factor for Coats disease; however, we acknowledged that this association may also be fortuitous given the few reported cases.
      In conclusion, this second case report of Coats disease associated with NF1 suggests that there may be an association between these entities. Further research into the pathogenesis of both conditions may elucidate the underlying mechanisms of this association.

      Consent for Publication

      The patient's parents gave verbal permission for the presentation of clinical details and images in this study. This report does not contain any personal information that could lead to the identification of the patient.

      Footnotes and Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

      Appendix. Supplementary materials

      References

        • Ferner R.E.
        • Huson S.M.
        • Thomas N.
        • et al.
        Guidelines for the diagnosis and management of individuals with neurofibromatosis 1.
        J Med Genet. 2007; 44: 81-88
        • Shields J.A.
        • Shields C.L.
        • Honavar S.G.
        • Demirci H.
        • Cater J.
        Classification and management of Coats disease: the 2000 Proctor Lecture.
        Am J Ophthalmol. 2001; 131: 572-583
        • Parrozzani R.
        • Pilotto E.
        • Clementi M.
        • Frizziero L.
        • Leonardi F.
        • Convento E.
        • et al.
        Retinal vascular abnormalities in a large cohort of patients affected by neurofibromatosis type 1.
        : A Study Using Optical Coherence Tomography Angiography. Retina (Philadelphia, Pa). 2018; 132: 585-593
        • Shields J.A.
        • Pellegrini M.
        • Kaliki S.
        • Mashayekhi A.
        • Shields C.L.
        Retinal vasoproliferative tumors in 6 patients with neurofibromatosis type 1.
        JAMA Ophthalmol. 2014; 132: 190
        • Zhang H.
        • Hudson F.Z.
        • Xu Z.
        • et al.
        Neurofibromin deficiency induces endothelial cell proliferation and retinal neovascularization.
        Invest Ophthalmol Vis Sci. 2018; 59: 2520-2528
        • Chiu S.L.
        • Chen S.N.
        • Chen Y.T.
        • Chen P.J.
        Coats’ disease and neovascular glaucoma in a child with neurofibromatosis.
        J Pediatr Ophthalmol Strabismus. 2011; 48: e1-3