Oliver R Marmoy1,2, Veronica A Kinsler3,4, Robert H Henderson5,4, Sian E Handley5,4, Will Moore5, Dorothy A Thompson5,4. 1. Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, UK. O.Marmoy@nhs.net. 2. Manchester Metropolitan University, Manchester, UK. O.Marmoy@nhs.net. 3. Paediatric Dermatology, Great Ormond Street Hospital for Children, London, UK. 4. UCL-GOSH Institute of Child Health, University College London, London, UK. 5. Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, UK.
Abstract
PURPOSE: Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, causing a disproportionate overgrowth of affected tissues. A small number of ocular complications have been reported. We present the unique findings in a patient who had molecular confirmation of AKT1 mosaicism alongside fulfilling the clinical criteria for Proteus syndrome. METHODS: Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics. RESULTS: Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina. CONCLUSION: We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation, either through disruption in the retinal PI3K-AKT1 signalling pathway or through mechanical distortion of ocular growth, resulting in disproportionate inner retinal development. The findings expand the ocular phenotype of Proteus syndrome and encourage early assessment to identify any incipient ocular abnormalities.
PURPOSE: Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, causing a disproportionate overgrowth of affected tissues. A small number of ocular complications have been reported. We present the unique findings in a patient who had molecular confirmation of AKT1 mosaicism alongside fulfilling the clinical criteria for Proteus syndrome. METHODS: Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics. RESULTS: Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina. CONCLUSION: We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation, either through disruption in the retinal PI3K-AKT1 signalling pathway or through mechanical distortion of ocular growth, resulting in disproportionate inner retinal development. The findings expand the ocular phenotype of Proteus syndrome and encourage early assessment to identify any incipient ocular abnormalities.
Authors: Jamie S Wee; Peter S Mortimer; Marjorie J Lindhurst; Heung Chong; Leslie G Biesecker; Colin A Holden Journal: JAMA Dermatol Date: 2014-09 Impact factor: 10.282
Authors: E A Bouzas; D Krasnewich; M Koutroumanidis; A Papadimitriou; J C Marini; M I Kaiser-Kupfer Journal: Ophthalmology Date: 1993-03 Impact factor: 12.079
Authors: Marjorie J Lindhurst; Julie C Sapp; Jamie K Teer; Jennifer J Johnston; Erin M Finn; Kathryn Peters; Joyce Turner; Jennifer L Cannons; David Bick; Laurel Blakemore; Catherine Blumhorst; Knut Brockmann; Peter Calder; Natasha Cherman; Matthew A Deardorff; David B Everman; Gretchen Golas; Robert M Greenstein; B Maya Kato; Kim M Keppler-Noreuil; Sergei A Kuznetsov; Richard T Miyamoto; Kurt Newman; David Ng; Kevin O'Brien; Steven Rothenberg; Douglas J Schwartzentruber; Virender Singhal; Roberto Tirabosco; Joseph Upton; Shlomo Wientroub; Elaine H Zackai; Kimberly Hoag; Tracey Whitewood-Neal; Pamela G Robey; Pamela L Schwartzberg; Thomas N Darling; Laura L Tosi; James C Mullikin; Leslie G Biesecker Journal: N Engl J Med Date: 2011-07-27 Impact factor: 91.245