Severe ophthalmic findings in arterial tortuosity syndrome, with SCL2A10 variant

Severe ophthalmic findings in arterial tortuosity syndrome, with SCL2A10 variant | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Severe ophthalmic findings in arterial tortuosity syndrome, with SCL2A10 variant Arnaud SIMON, Vincent Michaud, Caroline Rooryck-Thambo, Guillaume Jedraszak, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8742755/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder caused by pathogenic variants in SLC2A10 , which encodes the glucose transporter GLUT10. This deficiency disrupts elastic fiber integrity, primarily affecting the vasculature but also involving skin, skeleton, and ocular tissues. While vascular manifestations such as arterial elongation, tortuosity, and stenosis are well-documented, detailed ophthalmologic descriptions—particularly corneal involvement—remain limited in the literature. This case report addresses this gap by presenting severe corneal pathology in an adult patient with genetically confirmed ATS, highlighting the importance of comprehensive ocular evaluation in this syndrome. Case presentation A 45-year-old woman with no relevant family history presented with congenital multilevel pulmonary artery stenosis, scoliosis, and migraines. Physical examination revealed characteristic dysmorphic features, including a long face, beaked nose, and hypertelorism. Ophthalmologic assessment showed best-corrected visual acuity of 20/50 (right eye) and 20/200 (left eye), with high myopic astigmatism. Slit-lamp examination identified bilateral globular corneal protrusion, peripheral thinning, and neovascularization. Anterior segment optical coherence tomography confirmed extreme corneal thinning (69 µm and 89 µm at the thinnest points) and irregular topography, with mean keratometry values of 64 and 67.5 diopters. These findings were consistent with keratoglobus, a rare ectatic disorder. Genetic analysis revealed compound heterozygous SLC2A10 variants (c.243C>G/p.Ser81Arg and c.1334del/p.Gly445GlufsTer40), confirming ATS. Conclusions This case underscores the potential for severe corneal involvement in ATS, supported by detailed imaging and genetic confirmation. The documentation of keratoglobus with extreme corneal thinning expands the known ophthalmologic spectrum of ATS and emphasizes the need for systematic ocular screening in affected individuals. Early recognition of such manifestations may guide multidisciplinary management and improve long-term visual outcomes. Arterial tortuosity syndrome Corneal thinning Keratectasia Keratoconus Keratoglobus SLC2A10 variant Figures Figure 1 Figure 2 Figure 3 1. Background Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder caused by variants in SLC2A10 , a gene that encodes the facilitative glucose transporter GLUT10. This defect leads to severe elastin fragmentation, affecting all connective tissues, but mainly the vasculature. (1–3) Individuals with ATS typically present with vascular elongation, tortuosity, and stenosis and are at risk for aneurysm formation and arterial dissection involving large and medium-sized arteries. Additional connective tissue features may be identified in the skeleton, skin, and other elastic soft tissues.(1,2,4–7) Ophthalmic findings in patients with ATS include myopia, keratoconus, or keratoglobus (8–11) However, detailed ophthalmologic findings in patients with ATS such as corneal thickness measurements, corneal topography, and refraction, remain scarce in the literature. Here, we report a case of severe corneal involvement with detailed ophthalmologic findings in an adult patient diagnosed with ATS carrying variants in SLC2A10 . 2. Case presentation We report the case of a 45 year-old woman with no relevant family medical history. Her past medical history included congenital multilevel pulmonary arteries stenosis (distal on the left and proximal on the right), atrial situs solitus, atrioventricular concordance and minimal ventricular septal defect. She had previously undergone stenting of the right pulmonary artery. Additional medical conditions included scoliosis, migraines and endometriosis. She had previously undergone surgery to remove a bilateral blepharochalasis. General physical examination revealed characteristic dysmorphic features, including a long face, elongated philtrum, micrognathia, beaked nose, downslanting palpebral fissures, blepharophimosis and hypertelorism (Figure 1). Best corrected visual acuity was 20/50 in the right eye and 20/200 in the left eye. Subjective refraction was –2.50 (-8x100°) and –2.00 (-5,75 x105°), respectively. Slit-lamp examination showed a bilateral globular corneal protrusion associated with a gutter in the periphery, and peripheral corneal neovascularization. The anterior chamber and crystalline lens were unremarkable ( Figure 2). Anterior segment Optical Coherence Tomography (OCT) demonstrated extremely reduced corneal thickness with corneal thinnest point (CTP) values of 69 μm in the right eye and 89 μm in the left eye. Corneal topography showed high irregular astigmatism, with mean keratometry values of 64 and 67,5 diopters, and maximum keratometry values of 78,4 and 84,4 diopters for the right and left eyes, respectively (Figure 3). Fundus examination and intra-ocular pressure were normal. The clinical, pachymetric and topographical findings were consistent with keratoglobus, a rare bilateral, noninflammatory corneal ectatic disorder characterized by diffuse thinning, often more pronounced in the mid-periphery. Previous genetic analyses revealed normal array-CGH. Whole genome analysis revealed two compound heterozygous variants in SLC2A10 gene, confirming the diagnosis of ATS. First variant (c.243C>G/p.Ser81Arg) is a rare missense variant described pathogenic in Clinvar patient database (Clinvar ID 4588) inherited from her mother. Second variant (c.1334del/p.Gly445GlufsTer40)) is a rare frameshift variant described pathogenic in Clinvar patient database (Clinvar ID 4587) inherited from her father 3. Discussion ATS is a rare autosomal recessive connective tissue disorder caused by pathogenic variants in SLC2A10 .(10,12,13) In ATS, GLUT10 deficiency is thought to increase TGF-β signaling which causes elastin fragmentation and impaired cellular differentiation. (2,14) As a result, patients develop arterial stenosis, aneurysms, and dissection involving large- and medium-sized vessels. (15) In addition to vascular manifestations, skin laxity, inguinal hernias, joint laxity, and skeletal overgrowth reflect generalized connective tissue involvement as seen in other inherited elastinopathies. (6,10,12,16–19) Ocular involvement in ATS has been sporadically reported, with descriptions of myopia, keratoconus, and keratoglobus. However, most published cases lack complete and well-documented ophthalmologic examinations and references to ocular pathology were often made based on historical information alone. Furthermore, detailed corneal imaging and pachymetruc measurments are rarely reported. To our knowledge, this is the first case report describing such severe ocular findings supported by extensive clinical, topographical and tomographic documentation. (1,3,9,11,17,20,21) Abbreviations ATS : Arterial Tortuosity Syndrome SLC2A10 : Solute Carrier Family 2 Member 10 GLUT10 : Glucose Transporter 10 TGF-β : Transforming Growth Factor Beta OCT : Optical Coherence Tomography CTP : Corneal Thinnest Point Array-CGH : Array Comparative Genomic Hybridization VSD : Ventricular Septal Defect (communication interventriculaire) Declarations Ethics approval and consent to participate : This case report was conducted in accordance with the ethical standards of the Declaration of Helsinki Written informed consent was obtained from the patient for participation in this study and for the use of her clinical data and images for research purposes Consent for publication Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Availability of data and materials : All data and materials are available from the corresponding author upon reasonable request, in accordance with patient confidentiality and ethical guidelines. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding No funding support. Authors' contributions Arnaud Simon drafted the manuscript. Vincent Michaud and Valentine Saunier reviewed the manuscript. David Touboul and Valentine Saunier collected the ophthalmologic data. Vincent Michaud, Caroline Rooryck-Thambo, and Guillaume Jedraszak performed the genetic analyses. All authors read and approved the final manuscript. Acknowledgements This research was made possible through access to the data generated by the 2025 French Genomic Medicine Initiative Authors' information (optional) Arnaud SIMON, Valentine SAUNIER and David TOUBOUL avec ophtalmologists specialized in corneal pathologies Vincent Michaud, Caroline Rooryck-Thambo, and Guillaume Jedraszak are geneticians References Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. janv 2008;29(1):150‑8. Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. avr 2006;38(4):452‑7. Coucke PJ, Wessels MW, Van Acker P, Gardella R, Barlati S, Willems PJ, et al. Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13. J Med Genet. oct 2003;40(10):747‑51. Abdul Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz Ul Haque M, Teebi AS. A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr Oslo Nor 1992. avr 2003;92(4):456‑62. Franceschini P, Guala A, Licata D, Di Cara G, Franceschini D. Arterial tortuosity syndrome. Am J Med Genet. 13 mars 2000;91(2):141‑3. Ertugrul, A. Diffuse tortuosity and lengthening of the arteries. Circulation 1967;36:400–407. Ovid [Internet].. A family exhibiting arterial tortuosity syndrome... : Clinical Genetics Alharbi SS, Algorinees RM, Alshehri MA. Ophthalmic Manifestations of Arterial Tortuosity Syndrome: Case Series of Patient and Carriers. Cornea. 1 avr 2023;42(4):476‑81. Hasler S, Stürmer J, Kaufmann C. Keratoglobus and deep stromal corneal opacification in a case of arterial tortuosity syndrome. Klin Monatsbl Augenheilkd. avr 2011;228(4):345‑6. Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. janv 2008;29(1):150‑8. Hardin JS, Zarate YA, Callewaert B, Phillips PH, Warner DB. Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series. Ophthalmic Genet. 2018;39(1):29‑34. Zaidi SHE, Meyer S, Peltekova VD, Lindinger A, Teebi AS, Faiyaz-Ul-Haque M. A novel non-sense mutation in the SLC2A10 gene of an arterial tortuosity syndrome patient of Kurdish origin. Eur J Pediatr. juill 2009;168(7):867‑70. Faiyaz-Ul-Haque M, Zaidi SHE, Al-Sanna N, Alswaid A, Momenah T, Kaya N, et al. A novel missense and a recurrent mutation in SLC2A10 gene of patients affected with arterial tortuosity syndrome. Atherosclerosis. avr 2009;203(2):466‑71. Callewaert B, De Paepe A, Coucke P. Arterial Tortuosity Syndrome. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, éditeurs. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 Rivera IR, Gomes L, Moisés VA, Silva CC, Andrade JL, Carvalho AC. Multiple arterial anomalies in the newborn infant. Echocardiographic and angiographic diagnosis. Arq Bras Cardiol. août 2000;75(2):137‑44. Beuren AJ, Hort W, Kalbfleisch H, Müller H, Stoermer J. Dysplasia of the systemic and pulmonary arterial system with tortuosity and lengthening of the arteries. A new entity, diagnosed during life, and leading to coronary death in early childhood. Circulation. janv 1969;39(1):109‑15. Franceschini P, Guala A, Licata D, Di Cara G, Franceschini D. Arterial tortuosity syndrome. Am J Med Genet. 13 mars 2000;91(2):141‑3. Abdul Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz Ul Haque M, Teebi AS. A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr Oslo Nor 1992. avr 2003;92(4):456‑62. Wessels MW, Catsman-Berrevoets CE, Mancini GMS, Breuning MH, Hoogeboom JJM, Stroink H, et al. Three new families with arterial tortuosity syndrome. Am J Med Genet A. 1 déc 2004;131(2):134‑43. Gardella R, Zoppi N, Assanelli D, Muiesan ML, Barlati S, Colombi M. Exclusion of candidate genes in a family with arterial tortuosity syndrome. Am J Med Genet A. 30 avr 2004;126A(3):221‑8. Ritelli M, Chiarelli N, Dordoni C, Reffo E, Venturini M, Quinzani S, et al. Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review. BMC Med Genet. 6 nov 2014;15:122. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8742755","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":602587141,"identity":"14cb4375-d3e7-49a6-9b37-fcb7b9e4b630","order_by":0,"name":"Arnaud SIMON","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIiWNgGAWjYNACNjBiYPjAcICBQQLI4AELMz4gqIVxBqoWZgO8WsBKeIjRwj/77MHPPGUM9nxih489tqm5k9gg3Xzsw5sKu8QNB5jZPmDRInEuL1ma5xxDYpt0WrpxzrFniQ0yx5JnzjmTnDizgZl5BjZrzvAYSPO2MSSwSeeYSec2HE7cfyPHmJm3jTmxn4H/MDYd8md4jH8DtdiDtVgCtTRIgLT8q09sY2BmxqbF4AyPGcgWxjaQFka4FiCjH4cWQ6AWyznnJEB+SZPsOXbYGOQXxjnHjhvPbMauRQ7osBtvymzs5WcnH5P4UXNYFhhihxne1FTLbjjejFULLOCwCeLTMApGwSgYBaMALwAAjIBYv8VJOHgAAAAASUVORK5CYII=","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":true,"prefix":"","firstName":"Arnaud","middleName":"","lastName":"SIMON","suffix":""},{"id":602587142,"identity":"bc9a9594-636e-49a2-a40a-ecf13d60c6de","order_by":1,"name":"Vincent Michaud","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"Vincent","middleName":"","lastName":"Michaud","suffix":""},{"id":602587143,"identity":"88ff4944-f795-474b-ba8b-bccb1fdc492b","order_by":2,"name":"Caroline Rooryck-Thambo","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"Caroline","middleName":"","lastName":"Rooryck-Thambo","suffix":""},{"id":602587144,"identity":"27abc4df-2351-4bd1-ae81-f59a8108a34f","order_by":3,"name":"Guillaume Jedraszak","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Amiens-Picardie","correspondingAuthor":false,"prefix":"","firstName":"Guillaume","middleName":"","lastName":"Jedraszak","suffix":""},{"id":602587145,"identity":"14c708b0-8428-43fb-832a-d1d15d4eeb2a","order_by":4,"name":"Valentine SAUNIER","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"Valentine","middleName":"","lastName":"SAUNIER","suffix":""},{"id":602587146,"identity":"06fa1463-8735-43a8-8369-236b661e295c","order_by":5,"name":"David Touboul","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Touboul","suffix":""}],"badges":[],"createdAt":"2026-01-30 15:25:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8742755/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8742755/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104510741,"identity":"b1e0387a-f1e1-4c75-bfef-516d772dc140","added_by":"auto","created_at":"2026-03-12 15:56:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":493485,"visible":true,"origin":"","legend":"\u003cp\u003ePictures ofpatient [MV1] showing a long face, elongated philtrum, micrognathia, beaked nose, downslanting palpebral fissures, blepharophimosis and hypertelorism\u003c/p\u003e\n\u003cp\u003e[MV1]La patiente a acccepté la publication des photos donc on peut enlever les points noirs\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8742755/v1/4908e2511ef2c7f374c70033.png"},{"id":104510740,"identity":"76140f56-a2ca-4cb8-90f0-de54156c3abf","added_by":"auto","created_at":"2026-03-12 15:56:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":731145,"visible":true,"origin":"","legend":"\u003cp\u003eSlit lamp photographs\u003c/p\u003e\n\u003cp\u003eA. B. C. Right eye showing marked peripheral corneal thinnng \u0026nbsp;associated with peripheral corneal neovascularization, predominantly in the nasal and inferior quadrants\u003c/p\u003e\n\u003cp\u003eD. Left eye showing similar peripheral corneal thinning, with peripheral neovascularization.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8742755/v1/4627558c5319428b2039eee4.png"},{"id":104510742,"identity":"0357aee3-0df2-455a-9d70-45dd03e08627","added_by":"auto","created_at":"2026-03-12 15:56:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":144616,"visible":true,"origin":"","legend":"\u003cp\u003eAnterior Segment Optical Coherence Tomography (CASIA2-Tomey)\u003c/p\u003e\n\u003cp\u003eA. Right eye showing severe peripheral \u0026nbsp;corneal thinning with severe protusion, and stromal hyperreflectivity in the area of maximal thinning.\u003c/p\u003e\n\u003cp\u003eB. Left eye showing more pronounced peripheral thinning of the cornea with severe protrusion, and stromal hyperreflectivity.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8742755/v1/2c34a61ae4fee48f994ffc2f.png"},{"id":107049280,"identity":"97cc0cc5-67fb-4204-8621-6c520abcc388","added_by":"auto","created_at":"2026-04-16 07:59:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2461848,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8742755/v1/dacb9d0a-ecf2-4800-b8b2-aabdbcc5c694.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe ophthalmic findings in arterial tortuosity syndrome, with SCL2A10 variant","fulltext":[{"header":"1. Background","content":"\u003cp\u003eArterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder caused by variants in \u003cem\u003eSLC2A10\u003c/em\u003e, a gene that encodes the facilitative glucose transporter GLUT10. This defect leads to severe elastin fragmentation, affecting all connective tissues, but mainly the vasculature. (1\u0026ndash;3)\u003c/p\u003e \u003cp\u003eIndividuals with ATS typically present with vascular elongation, tortuosity, and stenosis and are at risk for aneurysm formation and arterial dissection involving large and medium-sized arteries. Additional connective tissue features may be identified in the skeleton, skin, and other elastic soft tissues.(1,2,4\u0026ndash;7)\u003c/p\u003e \u003cp\u003eOphthalmic findings in patients with ATS include myopia, keratoconus, or keratoglobus (8\u0026ndash;11)\u003c/p\u003e \u003cp\u003eHowever, detailed ophthalmologic findings in patients with ATS such as corneal thickness measurements, corneal topography, and refraction, remain scarce in the literature.\u003c/p\u003e \u003cp\u003eHere, we report a case of severe corneal involvement with detailed ophthalmologic findings in an adult patient diagnosed with ATS carrying variants in \u003cem\u003eSLC2A10\u003c/em\u003e.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eWe report the case of a 45 year-old woman with no relevant family medical history. Her past medical history included congenital multilevel pulmonary arteries stenosis (distal on the left and proximal on the right), atrial situs solitus, atrioventricular concordance and minimal ventricular septal defect. She had previously undergone stenting of the right pulmonary artery. Additional medical conditions included scoliosis, migraines and endometriosis. She had previously undergone surgery to remove a bilateral blepharochalasis.\u003c/p\u003e\n\u003cp\u003eGeneral physical examination revealed characteristic dysmorphic features, including a long face, elongated philtrum, micrognathia, beaked nose, downslanting palpebral fissures, blepharophimosis and hypertelorism \u003cem\u003e(Figure 1).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBest corrected visual acuity was 20/50 in the right eye and 20/200 in the left eye. Subjective refraction was –2.50 (-8x100°) and –2.00 (-5,75 x105°), respectively.\u003c/p\u003e\n\u003cp\u003eSlit-lamp examination showed a bilateral globular corneal protrusion associated with a gutter in the periphery, and peripheral corneal neovascularization. The anterior chamber and crystalline lens were unremarkable (\u003cem\u003eFigure 2).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAnterior segment Optical Coherence Tomography (OCT) demonstrated extremely reduced corneal thickness with corneal thinnest point (CTP) values of 69 μm in the right eye and 89 μm in the left eye. Corneal topography showed high irregular astigmatism, with mean keratometry values of 64 and 67,5 diopters, and maximum keratometry values of 78,4 and 84,4 diopters for the right and left eyes, respectively \u003cem\u003e(Figure 3).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFundus examination and intra-ocular pressure were normal.\u003c/p\u003e\n\u003cp\u003eThe clinical, pachymetric and topographical findings were consistent with \u0026nbsp;keratoglobus, a rare bilateral, noninflammatory corneal ectatic disorder characterized by diffuse thinning, often more pronounced in the mid-periphery.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Previous genetic analyses revealed normal array-CGH.\u003c/p\u003e\n\u003cp\u003eWhole genome analysis revealed two compound heterozygous variants in \u003cem\u003eSLC2A10\u003c/em\u003e gene, confirming the diagnosis of ATS. First variant (c.243C\u0026gt;G/p.Ser81Arg) is a rare missense variant described pathogenic in Clinvar patient database (Clinvar ID 4588) inherited from her mother. Second variant (c.1334del/p.Gly445GlufsTer40)) is a rare frameshift variant described pathogenic in Clinvar patient database (Clinvar ID 4587) inherited from her father\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eATS is a rare autosomal recessive connective tissue disorder caused by pathogenic variants in \u003cem\u003eSLC2A10\u003c/em\u003e.(10,12,13) In ATS, GLUT10 deficiency is thought to increase TGF-β signaling which causes elastin fragmentation and impaired cellular differentiation. (2,14) As a result, patients develop arterial stenosis, aneurysms, and dissection involving large- and medium-sized vessels. (15) In addition to vascular manifestations, skin laxity, inguinal hernias, joint laxity, and skeletal overgrowth reflect generalized connective tissue involvement as seen in other inherited elastinopathies. (6,10,12,16–19) Ocular involvement in ATS has been sporadically reported, with descriptions of myopia, keratoconus, and keratoglobus. However, most published cases lack complete and well-documented ophthalmologic examinations and references to ocular pathology were often made based on historical information alone. Furthermore, detailed corneal imaging and pachymetruc measurments are rarely reported.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the first case report describing such severe ocular findings supported by extensive clinical, topographical and tomographic documentation. (1,3,9,11,17,20,21)\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eATS\u003c/strong\u003e : Arterial Tortuosity Syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSLC2A10\u003c/strong\u003e : \u003cem\u003eSolute Carrier Family 2 Member 10\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGLUT10\u003c/strong\u003e : Glucose Transporter 10\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTGF-\u0026beta;\u003c/strong\u003e : \u003cem\u003eTransforming Growth Factor Beta\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOCT\u003c/strong\u003e : Optical Coherence Tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCTP\u003c/strong\u003e : Corneal Thinnest Point\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eArray-CGH\u003c/strong\u003e : \u003cem\u003eArray Comparative Genomic Hybridization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVSD\u003c/strong\u003e : Ventricular Septal Defect (communication interventriculaire)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was conducted in accordance with the ethical standards of the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for participation in this study and for the use of her clinical data and images for research purposes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eAll data and materials are available from the corresponding author upon reasonable request, in accordance with patient confidentiality and ethical guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArnaud Simon drafted the manuscript. Vincent Michaud and Valentine Saunier reviewed the manuscript. David Touboul and Valentine Saunier collected the ophthalmologic data. Vincent Michaud, Caroline Rooryck-Thambo, and Guillaume Jedraszak performed the genetic analyses. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was made possible through access to the data generated by the 2025 French Genomic Medicine Initiative\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArnaud SIMON, Valentine SAUNIER and David TOUBOUL avec ophtalmologists specialized in corneal pathologies\u003c/p\u003e\n\u003cp\u003eVincent Michaud, Caroline Rooryck-Thambo, and Guillaume Jedraszak are geneticians\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCallewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. janv 2008;29(1):150‑8. \u003c/li\u003e\n\u003cli\u003eCoucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. avr 2006;38(4):452‑7. \u003c/li\u003e\n\u003cli\u003eCoucke PJ, Wessels MW, Van Acker P, Gardella R, Barlati S, Willems PJ, et al. Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13. J Med Genet. oct 2003;40(10):747‑51. \u003c/li\u003e\n\u003cli\u003eAbdul Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz Ul Haque M, Teebi AS. A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr Oslo Nor 1992. avr 2003;92(4):456‑62. \u003c/li\u003e\n\u003cli\u003eFranceschini P, Guala A, Licata D, Di Cara G, Franceschini D. Arterial tortuosity syndrome. Am J Med Genet. 13 mars 2000;91(2):141‑3. \u003c/li\u003e\n\u003cli\u003eErtugrul, A. Diffuse tortuosity and lengthening of the arteries. Circulation 1967;36:400\u0026ndash;407. \u003c/li\u003e\n\u003cli\u003eOvid [Internet].. A family exhibiting arterial tortuosity syndrome... : Clinical Genetics\u003c/li\u003e\n\u003cli\u003eAlharbi SS, Algorinees RM, Alshehri MA. Ophthalmic Manifestations of Arterial Tortuosity Syndrome: Case Series of Patient and Carriers. Cornea. 1 avr 2023;42(4):476‑81. \u003c/li\u003e\n\u003cli\u003eHasler S, St\u0026uuml;rmer J, Kaufmann C. Keratoglobus and deep stromal corneal opacification in a case of arterial tortuosity syndrome. Klin Monatsbl Augenheilkd. avr 2011;228(4):345‑6. \u003c/li\u003e\n\u003cli\u003eCallewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. janv 2008;29(1):150‑8. \u003c/li\u003e\n\u003cli\u003eHardin JS, Zarate YA, Callewaert B, Phillips PH, Warner DB. Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series. Ophthalmic Genet. 2018;39(1):29‑34. \u003c/li\u003e\n\u003cli\u003eZaidi SHE, Meyer S, Peltekova VD, Lindinger A, Teebi AS, Faiyaz-Ul-Haque M. A novel non-sense mutation in the SLC2A10 gene of an arterial tortuosity syndrome patient of Kurdish origin. Eur J Pediatr. juill 2009;168(7):867‑70. \u003c/li\u003e\n\u003cli\u003eFaiyaz-Ul-Haque M, Zaidi SHE, Al-Sanna N, Alswaid A, Momenah T, Kaya N, et al. A novel missense and a recurrent mutation in SLC2A10 gene of patients affected with arterial tortuosity syndrome. Atherosclerosis. avr 2009;203(2):466‑71. \u003c/li\u003e\n\u003cli\u003eCallewaert B, De Paepe A, Coucke P. Arterial Tortuosity Syndrome. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, \u0026eacute;diteurs. GeneReviews\u0026reg; [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u003c/li\u003e\n\u003cli\u003eRivera IR, Gomes L, Mois\u0026eacute;s VA, Silva CC, Andrade JL, Carvalho AC. Multiple arterial anomalies in the newborn infant. Echocardiographic and angiographic diagnosis. Arq Bras Cardiol. ao\u0026ucirc;t 2000;75(2):137‑44. \u003c/li\u003e\n\u003cli\u003eBeuren AJ, Hort W, Kalbfleisch H, M\u0026uuml;ller H, Stoermer J. Dysplasia of the systemic and pulmonary arterial system with tortuosity and lengthening of the arteries. A new entity, diagnosed during life, and leading to coronary death in early childhood. Circulation. janv 1969;39(1):109‑15. \u003c/li\u003e\n\u003cli\u003eFranceschini P, Guala A, Licata D, Di Cara G, Franceschini D. Arterial tortuosity syndrome. Am J Med Genet. 13 mars 2000;91(2):141‑3. \u003c/li\u003e\n\u003cli\u003eAbdul Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz Ul Haque M, Teebi AS. A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr Oslo Nor 1992. avr 2003;92(4):456‑62. \u003c/li\u003e\n\u003cli\u003eWessels MW, Catsman-Berrevoets CE, Mancini GMS, Breuning MH, Hoogeboom JJM, Stroink H, et al. Three new families with arterial tortuosity syndrome. Am J Med Genet A. 1 d\u0026eacute;c 2004;131(2):134‑43. \u003c/li\u003e\n\u003cli\u003eGardella R, Zoppi N, Assanelli D, Muiesan ML, Barlati S, Colombi M. Exclusion of candidate genes in a family with arterial tortuosity syndrome. Am J Med Genet A. 30 avr 2004;126A(3):221‑8. \u003c/li\u003e\n\u003cli\u003eRitelli M, Chiarelli N, Dordoni C, Reffo E, Venturini M, Quinzani S, et al. Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review. BMC Med Genet. 6 nov 2014;15:122.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Arterial tortuosity syndrome, Corneal thinning, Keratectasia, Keratoconus, Keratoglobus, SLC2A10 variant ","lastPublishedDoi":"10.21203/rs.3.rs-8742755/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8742755/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder caused by pathogenic variants in \u003cem\u003eSLC2A10\u003c/em\u003e, which encodes the glucose transporter GLUT10. This deficiency disrupts elastic fiber integrity, primarily affecting the vasculature but also involving skin, skeleton, and ocular tissues. While vascular manifestations such as arterial elongation, tortuosity, and stenosis are well-documented, detailed ophthalmologic descriptions—particularly corneal involvement—remain limited in the literature. This case report addresses this gap by presenting severe corneal pathology in an adult patient with genetically confirmed ATS, highlighting the importance of comprehensive ocular evaluation in this syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 45-year-old woman with no relevant family history presented with congenital multilevel pulmonary artery stenosis, scoliosis, and migraines. Physical examination revealed characteristic dysmorphic features, including a long face, beaked nose, and hypertelorism. Ophthalmologic assessment showed best-corrected visual acuity of 20/50 (right eye) and 20/200 (left eye), with high myopic astigmatism. Slit-lamp examination identified bilateral globular corneal protrusion, peripheral thinning, and neovascularization. Anterior segment optical coherence tomography confirmed extreme corneal thinning (69 µm and 89 µm at the thinnest points) and irregular topography, with mean keratometry values of 64 and 67.5 diopters. These findings were consistent with keratoglobus, a rare ectatic disorder. Genetic analysis revealed compound heterozygous \u003cem\u003eSLC2A10\u003c/em\u003e variants (c.243C\u0026gt;G/p.Ser81Arg and c.1334del/p.Gly445GlufsTer40), confirming ATS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case underscores the potential for severe corneal involvement in ATS, supported by detailed imaging and genetic confirmation. The documentation of keratoglobus with extreme corneal thinning expands the known ophthalmologic spectrum of ATS and emphasizes the need for systematic ocular screening in affected individuals. Early recognition of such manifestations may guide multidisciplinary management and improve long-term visual outcomes.\u003c/p\u003e","manuscriptTitle":"Severe ophthalmic findings in arterial tortuosity syndrome, with SCL2A10 variant","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-12 15:55:57","doi":"10.21203/rs.3.rs-8742755/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8f95d89b-122d-4169-be77-1963d3e37ed1","owner":[],"postedDate":"March 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T07:57:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-12 15:55:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8742755","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8742755","identity":"rs-8742755","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}