- Email: [email protected]
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FIG 2. Magnetic resonance imaging. A, Axial T2-weighted image demonstrating hyperintense signal abnormalities (large arrows) throughout the white matter and deep gray structures. There are cystic changes (black arrowhead) and calcification (small arrows) within the bilateral thalami with additional calcifications (small arrows) in the right periatrial and occipital subcortical white matter. B, Post-contrast T1-weighted images of the brain demonstrating multifocal enhancement (large arrows) within the bilateral thalami and focal calcification (small arrow) within the right thalamus.
abnormalities and associated deafness and delayed milestones led to early neuroimaging. We conclude that neuroimaging should be performed when peripheral retinal vasculature abnormalities are associated with neurological or syndromic features, however mild or seemingly unrelated, because it is likely that the entire phenotype of this rare disease has not yet been identified.
References 1. Polvi A, Linnankivi T, Kivel€a T, et al. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am J Hum Genet 2012;90:540-49. 2. Anderson BH, Kasher PR, Mayer J, et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet 2012;44:338-42. 3. Linnankivi T, Valanne L, Paetau A, et al. Cerebroretinal microangiopathy with calcifications and cysts. Neurology 2006; 67:1437-43. 4. Toiviainen-Salo S, Linnankivi T, Saarinen A, M€ayr€anp€a€a MK, Karikoski R, M€akitie O. Cerebroretinal microangiopathy with calcifications and cysts: characterization of the skeletal phenotype. Am J Med Genet A 2011;155A:1322-8. 5. Linnankivi T, Polvi A, M€akitie O, Lehesjoki AE, Kivela T. Cerebroretinal microangiopathy with calcifications and cysts, Revesz syndrome and aplastic anemia. Bone Marrow Transplant 2013;48:153. 6. Jenkinson EM, Rodero MP, Kasher PR, et al. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet 2016;48:1185-92. 7. Takai H, Jenkinson E, Kabir S, et al. A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus. Genes Dev 2016;30:812-26. 8. Simon AJ, Lev A, Zhang Y, et al. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med 2016;213:1429-40. 9. Bisserbe A, Tertian G, Buffet C, et al. Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene. Rev Nuerol (Paris) 2015;171:445-9.
10. Briggs TA, Hubbard M, Hawkins C, et al. Treatment of gastrointestinal bleeding in a probable case of cerebroretinal microangiopathy with calcifications and cysts. Mol Syndromol 2011;1:159-62.
Revesz syndrome masquerading as traumatic retinal detachment Kareem Moussa, MD,a James N. Huang, MD,b and Anthony T. Moore, MA, FRCOphtha A 13-month-old boy with mild hemophilia A presented for strabismus evaluation and was found to have retinal hemorrhages in the right eye, left exotropia, and left total retinal detachment. These findings were attributed to trauma and hemophilia A. Routine blood work for hemophilia A subsequently showed pancytopenia. A bone marrow aspirate showed marked hypocellularity consistent with severe aplastic anemia, and telomere testing revealed very short telomeres. The patient was found to have a TINF2 mutation consistent with a diagnosis of Revesz syndrome, a variant of dyskeratosis
Author affiliations: a Department of Ophthalmology, University of California, San Francisco; bDepartment of Pediatrics, University of California, San Francisco, and UCSF Benioff Children’s Hospital Financial support: That Man May See Inc. This work was made possible in part, by NIH-NEI EY002162 - Core Grant for Vision Research and by the Research to Prevent Blindness Unrestricted Grant. Submitted September 15, 2016. Revision accepted April 25, 2017. Published online September 1, 2017. Correspondence: Anthony T. Moore, MA, FRCOphth, UCSF School of Medicine, Koret Vision Center, 10 Koret Way, San Francisco CA 94133 (email: [email protected]). J AAPOS 2017;21:422-425. Copyright Ó 2017, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2017.04.016
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congenita. He underwent successful bone marrow transplantation, and on subsequent evaluation was found to have retinal hemorrhages, vessel sclerosis, and cotton wool spots in the right eye associated with peripheral retinal nonperfusion. He underwent retinal laser treatment to the areas of retinal nonperfusion which resulted in stable visual function.
Case Report A 13-month-old boy with mild hemophilia A was seen at his local clinic for evaluation of intermittent left exotropia. Two months prior to presentation he had suffered accidental head trauma after falling on his head as he was squatting. Computed tomography (CT) of the brain at that time demonstrated intracranial calcifications of uncertain origin. On examination, he was able to fix and follow with the right eye and objected to occlusion of the right eye. A left exotropia was noted. Dilated fundus examination revealed an abnormal fundus in the left eye. He was referred to a pediatric retina specialist, who noted retinal hemorrhages temporal to the macula of the right eye and a total retinal detachment with preretinal fibrosis in the left eye; no retinal tear was identified. Although rhe cause of the retinal detachment was uncertain, it was thought to be possibly related to the recent head trauma and a propensity to bleeding due to hemophilia A. Retinal detachment surgery was unlikely to restore vision; observation was recommended. Two months later, routine blood testing showed pancytopenia. A bone marrow aspirate revealed hypocellularity consistent with severe aplastic anemia. Magnetic resonance imaging of the brain was performed because of concerns for developmental delay and showed the aforementioned intracranial calcification and cerebellar hypoplasia (Figure 1). Telomere testing revealed very short telomeres (\1%) in all cell types. Targeted gene sequence analysis revealed a heterozygous R282H mutation in the TINF2 gene, consistent with a diagnosis of Revesz syndrome. The patient was subsequently referred to University of California, San Francisco, where he underwent successful bone marrow transplantation. On evaluation at the age of 3 years, he was on topical dorzolamide in the left eye for secondary glaucoma. Visual acuity was 20/50 in the right eye by HOTV testing, and no light perception in the left eye. Intraocular pressure was 13 mm Hg in both eyes by iCare tonometry. Examination was notable for retinal hemorrhages and incomplete retinal vascularization in the right eye and a white cataract in the left eye. B-scan ultrasonography of the left eye confirmed a total retinal detachment. Inspection of the hands revealed dystrophic nails (eFigure 1). On examination under anesthesia, retinal hemorrhages and vessel sclerosis in the temporal periphery of the right
Journal of AAPOS
FIG 1. Magnetic resonance imaging (MRI) of the brain performed at 15 months of age. A, Axial T2 susceptibility–weighted angiography (SWAN) MRI showing multiple bilateral thalamic calcifications. B, Sagittal T1-weighted MRI showing cerebellar hypoplasia.
eye were noted (Figure 2A,B). Fluorescein angiography showed nonperfusion of the temporal retina (Figure 2C). Retinal laser was applied to the nonperfused retina (Figure 2D). Three months later, additional laser was applied in the nasal periphery adjacent to a new area of hemorrhage. At that time, optical coherence tomography showed subretinal hemorrhage and intraretinal cystic fluid in the temporal macula (Figure 3). At the most recent evaluation, 3 weeks later, visual acuity remained 20/50 in the right eye by HOTV testing.
Discussion Dyskeratosis congenita is a rare inherited bone marrow failure syndrome characterized by short telomeres. Dysplastic nails, lacy reticular pigmentation of the skin, and oral leukoplakia comprise the classic diagnostic triad, but the phenotype is variable and not all of these features are present in all cases.1 Revesz syndrome is a part of the dyskeratosis congenita spectrum is characterized by aplastic anemia, nail dystrophy, retinopathy, and central nervous system abnormalities such as cerebellar hypoplasia and intracranial calcification.2 This syndrome is caused by a mutation in the TINF2 gene, which encodes telomeric repeat binding protein 1 interacting protein (TIN2), which is involved in the maintenance of telomeres. It affects males three times more commonly than females, and most affected individuals develop aplastic anemia by 10 years of age.3 The reason for the male sex predilection is unknown. The pathophysiologic mechanisms that give rise to this phenotype remain unknown. A recent review on dyskeratosis congenita reported mutations in 13 genes linked to this disease, all of which are involved in telomere maintenance.4 The downstream effects that lead to the characteristic phenotypic changes are unclear.
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FIG 2. A, Fundus photograph of the right eye showing hemorrhages in the temporal macula and inferior retina, and cotton wool spots and vessel sclerosis in the temporal retina. B, High-magnification photograph of the right macula showing hemorrhage in the temporal macula, cotton wool spots, and vessel sheathing. C, Late-phase fluorescein angiography of the right eye showing non-perfusion in the temporal retina, and blockage by hemorrhage. D, Fundus photograph of the right eye following laser treatment.
FIG 3. Optical coherence tomography, horizontal scan, of the right macula showing subretinal hyperreflective material in the temporal macula consistent with subretinal hemorrhage, as well as cystic intraretinal fluid. The foveal contour is well preserved.
In 2010 Tsilou and colleagues5 reviewed the ocular and orbital manifestations of dyskeratosis congenita in 28 patients. The most common abnormalities involved the lacrimal system (29%), followed by the retina (21%), the eyelid (10.5%), and the lens (3.5%). The retinal abnormalities included retinal pigment epithelial changes, retinal neovascularization, retinal detachment, vascular sheathing, incomplete retinal vascularization, and exudative retinopathy. Other abnormalities included absence of puncta, nasolacrimal duct obstruction, cicatricial entropion, trichiasis, and cataracts. Our patient also has mild hemophilia A, a coincidental association, and the retinal findings on initial examination were incorrectly, but understandably, attributed to this diagnosis. The cause of the retinal
hemorrhages and the retinal detachment is likely to be secondary to peripheral retinal nonperfusion and neovascularization associated with dyskeratosis congenita, although the extent of the bleeding may have been influenced by the hemophilia. The retinal vascular changes of dyskeratosis congenita can precede the development of progressive bone marrow failure, on occasion by many months, making early specific diagnosis more difficult.6,7 References 1. Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol 2013;6:327-37. 2. Revesz T, Fletcher S, al-Gazali LI, DeBuse P. Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome? J Med Genet 1992;29:673-5. 3. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008;112:3594-600. 4. Gupta MP, Talcott KE, Kim DY, Agarwal S, Mukai S. Retinal findings and a novel TINF2 mutation in Revesz syndrome: clinical and molecular correlations with pediatric retinal vasculopathies. Ophthalmic Genet 2017;38:51-60. 5. Tsilou ET, Giri N, Weinstein S, Mueller C, Savage SA, Alter BP. Ocular and orbital manifestations of the inherited bone marrow failure syndromes: Fanconi anemia and dyskeratosis congenita. Ophthalmology 2010;117:615-22. 6. Teixeira LF, Shields CL, Marr B, Horgan N, Shields JA. Bilateral retinal vasculopathy in a patient with dyskeratosis congenita. Arch Ophthalmol 2008;126:134-5.
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7. Johnson CA, Hatfield M, Pulido JS. Retinal vasculopathy in a family with autosomal dominant dyskeratosis congenita. Ophthalmic Genet 2009;30:181-4.
Forceps trauma in a newborn presenting as iris heterochromia Sarah M. Simpson, MD,a Gary Yau, MD, FRCSC,a Kanwal K. Nischal, MD, FRCOphth,b and Yi Ning J. Strube, MD, MS, FRCSC, DABOa Birth-associated ocular trauma is common and often minor, including subconjunctival and retinal haemorrhage and eyelid edema. Significant ocular trauma during birth, usually associated with forceps-assisted delivery, is rarer and can include Descemet’s membrane rupture, lid lacerations, hyphema, Purtcher retinopathy, facial nerve palsy, corneal edema, and corneal laceration. We report the first case of ocular birth trauma from forceps presenting as isolated iris heterochromia and a pseudo rubeosis iridis, which completely resolved by 1 month of age with no known adverse ocular sequelae.
FIG 1. Iris heterochromia secondary to trauma in a 4-day-old girl. A, Right iris is hazel/brown secondary to heme in the iris stroma and overlying prominent iris vessels and fibrin in the anterior chamber. The left iris is blue and normal appearing, with no conjunctival hemorrhage or prominent iris vessels. Both corneas were clear. Note resolving forceps-induced indented scar on forehead, right of midline. B, Right eye, showing conjunctival hemorrhage medially, prominent iris vessels at the pupillary margin, iris stromal heme, and hazel/brown iris coloration. The conjunctiva was friable and easily bled with minimal manipulation; a small amount of blood can be seen on palpebral conjunctiva from use of the eyelid speculum.
Case Report An infant girl was born at 41 weeks’ gestational age, the result of a normal pregnancy, weighing 3700 g. Forceps assistance was required during vaginal delivery due to left occiput anterior positioning; there was no shoulder dystocia or other complications during delivery. The mother noted right upper eyelid swelling and cloudy appearance of the right eye immediately following delivery. The child was otherwise systemically well. Family history was negative for ocular disease. On routine screening examination, an absent red reflex of the right eye was noted by the pediatrician. An ophthalmic assessment was completed at 4 days of age in the Department of Ophthalmology, Hotel Dieu Hospital, Kingston, Ontario. Gross examination revealed a rightsided mid-forehead indented scar secondary to forceps use. Eyelids and periorbita were normal, with no ptosis, swelling, or pigmented lesions. The pupils appeared equally round and reactive to light prior to dilation, with
Author affiliations: aDepartment of Ophthalmology, Queen’s University, Kingston, Ontario, Canada; bDepartment of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Submitted March 9, 2017. Revision accepted June 7, 2017. Published online September 1, 2017. Correspondence: Dr. Yi Ning J. Strube, MD, MS, FRCSC, DABO, Department of Ophthalmology, Queen’s University, Hotel Dieu Hospital, 166 Brock Street, Kingston, ON, K7L 5G2 Canada (email: [email protected]). J AAPOS 2017;21:425-426. Copyright Ó 2017, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2017.06.015
Journal of AAPOS
FIG 2. Photograph of patient’s eyes taken at 6 months of age showing symmetry of iris pigmentation. Corneal diameters were 11.0 mm in each eye, with normal intraocular pressures bilaterally.
no anisocoria in both light and dark settings noted, no relative afferent pupillary defect, and a normal red reflex in both eyes. However, after dilation with cyclopentolate hydrochloride 0.2%, phenylephrine hydrochloride 1% eyedrops, the right pupil only dilated 5 mm compared to 7.5 mm on the left. Intraocular pressure, measured using the iCare PRO tonometer (ICare Finland Oy), was normal in both eyes, 12.5 mm Hg in the right eye and 12.8 mm Hg in the left eye. There was a faint subconjunctival hemorrhage medially in the right eye. Horizontal corneal diameters measured 11 mm in each eye. Corneas were clear, with no Descemet’s membrane rupture. The anterior chambers were deep and well formed, with no anterior chamber cell or flare seen bilaterally; however, there were fibrin strands overlying the anterior lens capsule. Iris heterochromia was present, with a darker iris and prominent stromal iris vessels on the right compared to a normal blue iris on the left (Figure 1A). Fine lacy vessels were seen at the iris pupillary margin, similar to typical iris rubeosis (Figure 1B). Dilated fundus examination was unremarkable, with no evidence of retinal or vitreous hemorrhage, intraocular mass, or neovascularization. A- and B-scan ultrasounds and ultrasound biomicroscopy were performed to rule out intraocular masses, including choroidal hemangioma, and were unremarkable.
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eFIG 1. Photograph of the patient’s left hand showing dystrophic nails, obtained at 3 years of age.
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FIG 2. Magnetic resonance imaging. A, Axial T2-weighted image demonstrating hyperintense signal abnormalities (large arrows) throughout the white matter and deep gray structures. There are cystic changes (black arrowhead) and calcification (small arrows) within the bilateral thalami with additional calcifications (small arrows) in the right periatrial and occipital subcortical white matter. B, Post-contrast T1-weighted images of the brain demonstrating multifocal enhancement (large arrows) within the bilateral thalami and focal calcification (small arrow) within the right thalamus.
abnormalities and associated deafness and delayed milestones led to early neuroimaging. We conclude that neuroimaging should be performed when peripheral retinal vasculature abnormalities are associated with neurological or syndromic features, however mild or seemingly unrelated, because it is likely that the entire phenotype of this rare disease has not yet been identified.
References 1. Polvi A, Linnankivi T, Kivel€a T, et al. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am J Hum Genet 2012;90:540-49. 2. Anderson BH, Kasher PR, Mayer J, et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet 2012;44:338-42. 3. Linnankivi T, Valanne L, Paetau A, et al. Cerebroretinal microangiopathy with calcifications and cysts. Neurology 2006; 67:1437-43. 4. Toiviainen-Salo S, Linnankivi T, Saarinen A, M€ayr€anp€a€a MK, Karikoski R, M€akitie O. Cerebroretinal microangiopathy with calcifications and cysts: characterization of the skeletal phenotype. Am J Med Genet A 2011;155A:1322-8. 5. Linnankivi T, Polvi A, M€akitie O, Lehesjoki AE, Kivela T. Cerebroretinal microangiopathy with calcifications and cysts, Revesz syndrome and aplastic anemia. Bone Marrow Transplant 2013;48:153. 6. Jenkinson EM, Rodero MP, Kasher PR, et al. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet 2016;48:1185-92. 7. Takai H, Jenkinson E, Kabir S, et al. A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus. Genes Dev 2016;30:812-26. 8. Simon AJ, Lev A, Zhang Y, et al. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med 2016;213:1429-40. 9. Bisserbe A, Tertian G, Buffet C, et al. Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene. Rev Nuerol (Paris) 2015;171:445-9.
10. Briggs TA, Hubbard M, Hawkins C, et al. Treatment of gastrointestinal bleeding in a probable case of cerebroretinal microangiopathy with calcifications and cysts. Mol Syndromol 2011;1:159-62.
Revesz syndrome masquerading as traumatic retinal detachment Kareem Moussa, MD,a James N. Huang, MD,b and Anthony T. Moore, MA, FRCOphtha A 13-month-old boy with mild hemophilia A presented for strabismus evaluation and was found to have retinal hemorrhages in the right eye, left exotropia, and left total retinal detachment. These findings were attributed to trauma and hemophilia A. Routine blood work for hemophilia A subsequently showed pancytopenia. A bone marrow aspirate showed marked hypocellularity consistent with severe aplastic anemia, and telomere testing revealed very short telomeres. The patient was found to have a TINF2 mutation consistent with a diagnosis of Revesz syndrome, a variant of dyskeratosis
Author affiliations: a Department of Ophthalmology, University of California, San Francisco; bDepartment of Pediatrics, University of California, San Francisco, and UCSF Benioff Children’s Hospital Financial support: That Man May See Inc. This work was made possible in part, by NIH-NEI EY002162 - Core Grant for Vision Research and by the Research to Prevent Blindness Unrestricted Grant. Submitted September 15, 2016. Revision accepted April 25, 2017. Published online September 1, 2017. Correspondence: Anthony T. Moore, MA, FRCOphth, UCSF School of Medicine, Koret Vision Center, 10 Koret Way, San Francisco CA 94133 (email: [email protected]). J AAPOS 2017;21:422-425. Copyright Ó 2017, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2017.04.016
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congenita. He underwent successful bone marrow transplantation, and on subsequent evaluation was found to have retinal hemorrhages, vessel sclerosis, and cotton wool spots in the right eye associated with peripheral retinal nonperfusion. He underwent retinal laser treatment to the areas of retinal nonperfusion which resulted in stable visual function.
Case Report A 13-month-old boy with mild hemophilia A was seen at his local clinic for evaluation of intermittent left exotropia. Two months prior to presentation he had suffered accidental head trauma after falling on his head as he was squatting. Computed tomography (CT) of the brain at that time demonstrated intracranial calcifications of uncertain origin. On examination, he was able to fix and follow with the right eye and objected to occlusion of the right eye. A left exotropia was noted. Dilated fundus examination revealed an abnormal fundus in the left eye. He was referred to a pediatric retina specialist, who noted retinal hemorrhages temporal to the macula of the right eye and a total retinal detachment with preretinal fibrosis in the left eye; no retinal tear was identified. Although rhe cause of the retinal detachment was uncertain, it was thought to be possibly related to the recent head trauma and a propensity to bleeding due to hemophilia A. Retinal detachment surgery was unlikely to restore vision; observation was recommended. Two months later, routine blood testing showed pancytopenia. A bone marrow aspirate revealed hypocellularity consistent with severe aplastic anemia. Magnetic resonance imaging of the brain was performed because of concerns for developmental delay and showed the aforementioned intracranial calcification and cerebellar hypoplasia (Figure 1). Telomere testing revealed very short telomeres (\1%) in all cell types. Targeted gene sequence analysis revealed a heterozygous R282H mutation in the TINF2 gene, consistent with a diagnosis of Revesz syndrome. The patient was subsequently referred to University of California, San Francisco, where he underwent successful bone marrow transplantation. On evaluation at the age of 3 years, he was on topical dorzolamide in the left eye for secondary glaucoma. Visual acuity was 20/50 in the right eye by HOTV testing, and no light perception in the left eye. Intraocular pressure was 13 mm Hg in both eyes by iCare tonometry. Examination was notable for retinal hemorrhages and incomplete retinal vascularization in the right eye and a white cataract in the left eye. B-scan ultrasonography of the left eye confirmed a total retinal detachment. Inspection of the hands revealed dystrophic nails (eFigure 1). On examination under anesthesia, retinal hemorrhages and vessel sclerosis in the temporal periphery of the right
Journal of AAPOS
FIG 1. Magnetic resonance imaging (MRI) of the brain performed at 15 months of age. A, Axial T2 susceptibility–weighted angiography (SWAN) MRI showing multiple bilateral thalamic calcifications. B, Sagittal T1-weighted MRI showing cerebellar hypoplasia.
eye were noted (Figure 2A,B). Fluorescein angiography showed nonperfusion of the temporal retina (Figure 2C). Retinal laser was applied to the nonperfused retina (Figure 2D). Three months later, additional laser was applied in the nasal periphery adjacent to a new area of hemorrhage. At that time, optical coherence tomography showed subretinal hemorrhage and intraretinal cystic fluid in the temporal macula (Figure 3). At the most recent evaluation, 3 weeks later, visual acuity remained 20/50 in the right eye by HOTV testing.
Discussion Dyskeratosis congenita is a rare inherited bone marrow failure syndrome characterized by short telomeres. Dysplastic nails, lacy reticular pigmentation of the skin, and oral leukoplakia comprise the classic diagnostic triad, but the phenotype is variable and not all of these features are present in all cases.1 Revesz syndrome is a part of the dyskeratosis congenita spectrum is characterized by aplastic anemia, nail dystrophy, retinopathy, and central nervous system abnormalities such as cerebellar hypoplasia and intracranial calcification.2 This syndrome is caused by a mutation in the TINF2 gene, which encodes telomeric repeat binding protein 1 interacting protein (TIN2), which is involved in the maintenance of telomeres. It affects males three times more commonly than females, and most affected individuals develop aplastic anemia by 10 years of age.3 The reason for the male sex predilection is unknown. The pathophysiologic mechanisms that give rise to this phenotype remain unknown. A recent review on dyskeratosis congenita reported mutations in 13 genes linked to this disease, all of which are involved in telomere maintenance.4 The downstream effects that lead to the characteristic phenotypic changes are unclear.
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FIG 2. A, Fundus photograph of the right eye showing hemorrhages in the temporal macula and inferior retina, and cotton wool spots and vessel sclerosis in the temporal retina. B, High-magnification photograph of the right macula showing hemorrhage in the temporal macula, cotton wool spots, and vessel sheathing. C, Late-phase fluorescein angiography of the right eye showing non-perfusion in the temporal retina, and blockage by hemorrhage. D, Fundus photograph of the right eye following laser treatment.
FIG 3. Optical coherence tomography, horizontal scan, of the right macula showing subretinal hyperreflective material in the temporal macula consistent with subretinal hemorrhage, as well as cystic intraretinal fluid. The foveal contour is well preserved.
In 2010 Tsilou and colleagues5 reviewed the ocular and orbital manifestations of dyskeratosis congenita in 28 patients. The most common abnormalities involved the lacrimal system (29%), followed by the retina (21%), the eyelid (10.5%), and the lens (3.5%). The retinal abnormalities included retinal pigment epithelial changes, retinal neovascularization, retinal detachment, vascular sheathing, incomplete retinal vascularization, and exudative retinopathy. Other abnormalities included absence of puncta, nasolacrimal duct obstruction, cicatricial entropion, trichiasis, and cataracts. Our patient also has mild hemophilia A, a coincidental association, and the retinal findings on initial examination were incorrectly, but understandably, attributed to this diagnosis. The cause of the retinal
hemorrhages and the retinal detachment is likely to be secondary to peripheral retinal nonperfusion and neovascularization associated with dyskeratosis congenita, although the extent of the bleeding may have been influenced by the hemophilia. The retinal vascular changes of dyskeratosis congenita can precede the development of progressive bone marrow failure, on occasion by many months, making early specific diagnosis more difficult.6,7 References 1. Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol 2013;6:327-37. 2. Revesz T, Fletcher S, al-Gazali LI, DeBuse P. Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome? J Med Genet 1992;29:673-5. 3. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008;112:3594-600. 4. Gupta MP, Talcott KE, Kim DY, Agarwal S, Mukai S. Retinal findings and a novel TINF2 mutation in Revesz syndrome: clinical and molecular correlations with pediatric retinal vasculopathies. Ophthalmic Genet 2017;38:51-60. 5. Tsilou ET, Giri N, Weinstein S, Mueller C, Savage SA, Alter BP. Ocular and orbital manifestations of the inherited bone marrow failure syndromes: Fanconi anemia and dyskeratosis congenita. Ophthalmology 2010;117:615-22. 6. Teixeira LF, Shields CL, Marr B, Horgan N, Shields JA. Bilateral retinal vasculopathy in a patient with dyskeratosis congenita. Arch Ophthalmol 2008;126:134-5.
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Simpson et al
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7. Johnson CA, Hatfield M, Pulido JS. Retinal vasculopathy in a family with autosomal dominant dyskeratosis congenita. Ophthalmic Genet 2009;30:181-4.
Forceps trauma in a newborn presenting as iris heterochromia Sarah M. Simpson, MD,a Gary Yau, MD, FRCSC,a Kanwal K. Nischal, MD, FRCOphth,b and Yi Ning J. Strube, MD, MS, FRCSC, DABOa Birth-associated ocular trauma is common and often minor, including subconjunctival and retinal haemorrhage and eyelid edema. Significant ocular trauma during birth, usually associated with forceps-assisted delivery, is rarer and can include Descemet’s membrane rupture, lid lacerations, hyphema, Purtcher retinopathy, facial nerve palsy, corneal edema, and corneal laceration. We report the first case of ocular birth trauma from forceps presenting as isolated iris heterochromia and a pseudo rubeosis iridis, which completely resolved by 1 month of age with no known adverse ocular sequelae.
FIG 1. Iris heterochromia secondary to trauma in a 4-day-old girl. A, Right iris is hazel/brown secondary to heme in the iris stroma and overlying prominent iris vessels and fibrin in the anterior chamber. The left iris is blue and normal appearing, with no conjunctival hemorrhage or prominent iris vessels. Both corneas were clear. Note resolving forceps-induced indented scar on forehead, right of midline. B, Right eye, showing conjunctival hemorrhage medially, prominent iris vessels at the pupillary margin, iris stromal heme, and hazel/brown iris coloration. The conjunctiva was friable and easily bled with minimal manipulation; a small amount of blood can be seen on palpebral conjunctiva from use of the eyelid speculum.
Case Report An infant girl was born at 41 weeks’ gestational age, the result of a normal pregnancy, weighing 3700 g. Forceps assistance was required during vaginal delivery due to left occiput anterior positioning; there was no shoulder dystocia or other complications during delivery. The mother noted right upper eyelid swelling and cloudy appearance of the right eye immediately following delivery. The child was otherwise systemically well. Family history was negative for ocular disease. On routine screening examination, an absent red reflex of the right eye was noted by the pediatrician. An ophthalmic assessment was completed at 4 days of age in the Department of Ophthalmology, Hotel Dieu Hospital, Kingston, Ontario. Gross examination revealed a rightsided mid-forehead indented scar secondary to forceps use. Eyelids and periorbita were normal, with no ptosis, swelling, or pigmented lesions. The pupils appeared equally round and reactive to light prior to dilation, with
Author affiliations: aDepartment of Ophthalmology, Queen’s University, Kingston, Ontario, Canada; bDepartment of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Submitted March 9, 2017. Revision accepted June 7, 2017. Published online September 1, 2017. Correspondence: Dr. Yi Ning J. Strube, MD, MS, FRCSC, DABO, Department of Ophthalmology, Queen’s University, Hotel Dieu Hospital, 166 Brock Street, Kingston, ON, K7L 5G2 Canada (email: [email protected]). J AAPOS 2017;21:425-426. Copyright Ó 2017, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2017.06.015
Journal of AAPOS
FIG 2. Photograph of patient’s eyes taken at 6 months of age showing symmetry of iris pigmentation. Corneal diameters were 11.0 mm in each eye, with normal intraocular pressures bilaterally.
no anisocoria in both light and dark settings noted, no relative afferent pupillary defect, and a normal red reflex in both eyes. However, after dilation with cyclopentolate hydrochloride 0.2%, phenylephrine hydrochloride 1% eyedrops, the right pupil only dilated 5 mm compared to 7.5 mm on the left. Intraocular pressure, measured using the iCare PRO tonometer (ICare Finland Oy), was normal in both eyes, 12.5 mm Hg in the right eye and 12.8 mm Hg in the left eye. There was a faint subconjunctival hemorrhage medially in the right eye. Horizontal corneal diameters measured 11 mm in each eye. Corneas were clear, with no Descemet’s membrane rupture. The anterior chambers were deep and well formed, with no anterior chamber cell or flare seen bilaterally; however, there were fibrin strands overlying the anterior lens capsule. Iris heterochromia was present, with a darker iris and prominent stromal iris vessels on the right compared to a normal blue iris on the left (Figure 1A). Fine lacy vessels were seen at the iris pupillary margin, similar to typical iris rubeosis (Figure 1B). Dilated fundus examination was unremarkable, with no evidence of retinal or vitreous hemorrhage, intraocular mass, or neovascularization. A- and B-scan ultrasounds and ultrasound biomicroscopy were performed to rule out intraocular masses, including choroidal hemangioma, and were unremarkable.
Volume 21 Number 5 / October 2017
eFIG 1. Photograph of the patient’s left hand showing dystrophic nails, obtained at 3 years of age.
Journal of AAPOS
Moussa, Huang, and Moore
425.e1