Myotonic Dystrophy 1 Complicated with Tetralogy of Fallot: A Rare Clinical Case Report

Myotonic Dystrophy 1 Complicated with Tetralogy of Fallot: A Rare Clinical Case Report | 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 Myotonic Dystrophy 1 Complicated with Tetralogy of Fallot: A Rare Clinical Case Report Fangzheng Chen, Benyan Zhang, Rujing Ren, Xiaoyu Xin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9506307/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 No abstract for letters . Neurology No keywords for letters. Figures Figure 1 Full Text Type 1 myotonic dystrophy (DM1) is an autosomal dominant hereditary muscular disorder caused by abnormal expansion of the trinucleotide CTG in the dystrophic myotonia protein kinase (DMPK) gene. 1 Tetralogy of Fallot (TOF) is a common congenital heart disease (CHD). 2 The co-existence of DM1 and TOF is extremely rare. Here, we present the first genetically and clinically fully confirmed case of adult-onset DM1 complicated with TOF, aiming to expand the clinical spectrum of DM1-associated comorbidities and explore their potential association and clinical implications. A 36-year-old male presented with a chronic onset of progressive hand weakness and lower limb myoatrophy for more than 2 years, accompanied by slurred speech and incomplete eyelid closure. No family history of hereditary diseases was noted. No treatment was given. Physical examination revealed distal weakness of both upper limbs with inability to clench fists, and marked atrophy of the bilateral tibialis anterior muscles (right > left), which was radiologically confirmed by lower limb MRI ( Fig. 1A ). The patient also exhibited significant alopecia and a hatchet face due to bilateral buccinator muscle atrophy, which are classic facial manifestations of DM1. Lower limb electromyography revealed myogenic myoelectric damage with widespread myotonic discharges. Cardiac echocardiography identified classic TOF (aortic overriding, right ventricular hypertrophy, perimembranous ventricular septal defect, and right ventricular outflow tract obstruction; Fig. 1B ). Right tibialis anterior muscle biopsy showed muscular dystrophy features ( Fig. 1C ). Whole-exome sequencing confirmed DM1 (DMPK CTG repeats: 12 and >50); family genetic testing was declined. The patient also had diabetes mellitus, incomplete right bundle branch block, first-degree atrioventricular block, Hashimoto’s thyroiditis, hyperhomocysteinemia, and hyperlipidemia, reflecting the multisystem nature of DM1. Cardiac surgical correction for TOF was recommended by surgeons but declined by the patient. The clinical presentation of this patient was consistent with the adult-onset DM1. 4 Prior to this report, Klompe L et al. described a case of DM1 complicated by TOF in a patient who underwent cardiac surgery, but the diagnosis of DM1 in that study lacked genetic and pathological confirmation. 3 The authors of that study speculated that the coexistence of DM1 and TOF was a coincidental event, a conclusion limited by the lack of definitive DM1 diagnostic evidence. However, our study provides comprehensive evidence confirming both DM1 and TOF, representing the first fully validated case of this rare comorbidity in a DM1 patient. This finding challenges the previous hypothesis of mere coincidence and suggests a potential non-random association between DM1 and congenital conotruncal heart malformations such as TOF. We postulate DMPK, beyond its neuromuscular role, may function in embryonic cardiac conotruncal development; abnormal CTG expansion may disrupt cardiac morphogenesis-related molecules, elevating CHD risk. Alternatively, DM1-associated multisystem developmental perturbations may create an embryonic milieu predisposing to cardiac malformation. This case expands DM1’s cardiac comorbidity spectrum and highlights the need for comprehensive cardiac imaging screening and multidisciplinary follow-up in DM1 patients. Future cohort and molecular studies are warranted to elucidate the DM1-CHD mechanistic link, providing a basis for early screening and personalized management of DM1 patients with cardiac comorbidities. Declarations Acknowledgments We appreciate our cooperative and collaborative patient and his family, and their permission to publish this case. Data availability statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding This study was supported by Youth Cultivation Program of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (2025PY125). References Kuntawala DH, Vitorino R, Cruz AC, Martins F, Rebelo S. Multisystem Symptoms in Myotonic Dystrophy Type 1: A Management and Therapeutic Perspective. Int J Mol Sci . 2025; 26 . Khan SM, Drury NE, Stickley J, Barron DJ, Brawn WJ, Jones TJ , et al. Tetralogy of Fallot: morphological variations and implications for surgical repair. Eur J Cardiothorac Surg . 2019; 56 : 101-09. Klompe L, Lancé M, van der Woerd D, Scohy T, Bogers AJ. Anaesthesiological and ventilatory precautions during cardiac surgery in Steinert's disease. J Card Surg . 2007; 22 : 74-75. Hartman, J., Patki, T. & Johnson, N. E. Diagnosis and Management of Myotonic Dystrophy Type 1. JAMA 331 , 1227-1228 (2024). Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9506307","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":628351714,"identity":"35999658-5e31-4666-bf28-5a3988ae7ac0","order_by":0,"name":"Fangzheng Chen","email":"","orcid":"","institution":"Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fangzheng","middleName":"","lastName":"Chen","suffix":""},{"id":628356399,"identity":"0c15706e-f630-4b64-a390-3f2939ff2be5","order_by":1,"name":"Benyan Zhang","email":"","orcid":"","institution":"Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Benyan","middleName":"","lastName":"Zhang","suffix":""},{"id":628356400,"identity":"459d07a6-fe0d-40bc-a7dd-3359d254613e","order_by":2,"name":"Rujing Ren","email":"","orcid":"","institution":"Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Rujing","middleName":"","lastName":"Ren","suffix":""},{"id":628356401,"identity":"ea0d6956-f75c-4faf-868a-a560272f1bf9","order_by":3,"name":"Xiaoyu Xin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACZgglx8bMkPggoaKGeC3G/OwNjw0enDlGvGWJM3sOPpN82MJMWKnBceaHj3nbDjNuuJGcVpHYwMbA396dgFeLZDObsTFvWxqzwY20tBuJO2QYJM6c3YBXCz8zg5k0b5sNm8GNHKCWM2wMBhK5+LWwMbN/A2qR4DG4kf+tILGNmbAWfmYesC0Skj0H0hiI0iLZzFNsOOdcmgEwkJMlEs4c4yHoF4Pzxzc+eFN2uB5ofuLHHxU1cvztvfi1gAATDxKHB6cyZMD4gyhlo2AUjIJRMGIBACGwRcPoJujcAAAAAElFTkSuQmCC","orcid":"","institution":"Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Xin","suffix":""}],"badges":[],"createdAt":"2026-04-23 11:47:42","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9506307/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9506307/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107697037,"identity":"016a6c10-0294-4e98-ace1-7e661ec763fa","added_by":"auto","created_at":"2026-04-24 07:19:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3498899,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical presentation of the patient. (A) \u003c/strong\u003eT2-weighted MRI showing right tibialis anterior atrophy (white arrow). \u003cstrong\u003e(B) \u003c/strong\u003eEchocardiogram showing obvious overriding aorta and ventricular septal defect (white arrow). RV: right ventricle. LV: left ventricle. LA: left atrium. AO: aorta.\u003cstrong\u003e \u003c/strong\u003eVSD: ventricular septal defect. \u003cstrong\u003e(C) \u003c/strong\u003eMuscle biopsy showing fiber atrophy (black arrowheads) and myonuclear internalization (*). Scale bar: 2000 μm.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9506307/v1/cc8b9ca82ca4dc3dba518e7c.png"},{"id":107707671,"identity":"2994c630-0dba-4d15-ae0a-b01b1869f745","added_by":"auto","created_at":"2026-04-24 09:20:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4830134,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9506307/v1/feeede87-55a5-4af0-9039-3876db90f70b.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eMyotonic Dystrophy 1 Complicated with Tetralogy of Fallot: A Rare Clinical Case Report\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eType 1 myotonic dystrophy (DM1) is an autosomal dominant hereditary muscular disorder caused by abnormal expansion of the trinucleotide CTG in the dystrophic myotonia protein kinase (DMPK) gene.\u003csup\u003e1\u003c/sup\u003e Tetralogy of Fallot (TOF) is a common congenital heart disease (CHD).\u003csup\u003e2\u003c/sup\u003e The co-existence of DM1 and TOF is extremely rare. Here, we present the first genetically and clinically fully confirmed case of adult-onset DM1 complicated with TOF, aiming to expand the clinical spectrum of DM1-associated comorbidities and explore their potential association and clinical implications.\u003c/p\u003e\n\u003cp\u003eA 36-year-old male presented with a chronic onset of progressive hand weakness and lower limb myoatrophy for more than 2 years, accompanied by slurred speech and incomplete eyelid closure. No family history of hereditary diseases was noted. No treatment was given. Physical examination revealed distal weakness of both upper limbs with inability to clench fists, and marked atrophy of the bilateral tibialis anterior muscles (right \u0026gt; left), which was radiologically confirmed by lower limb MRI (\u003cstrong\u003eFig. 1A\u003c/strong\u003e). The patient also exhibited significant alopecia and a hatchet face due to bilateral buccinator muscle atrophy, which are classic facial manifestations of DM1. Lower limb electromyography revealed myogenic myoelectric damage with widespread myotonic discharges. Cardiac echocardiography identified classic TOF (aortic overriding, right ventricular hypertrophy, perimembranous ventricular septal defect, and right ventricular outflow tract obstruction; \u003cstrong\u003eFig. 1B\u003c/strong\u003e). Right tibialis anterior muscle biopsy showed muscular dystrophy features (\u003cstrong\u003eFig. 1C\u003c/strong\u003e). Whole-exome sequencing confirmed DM1 (DMPK CTG repeats: 12 and \u0026gt;50); family genetic testing was declined. The patient also had diabetes mellitus, incomplete right bundle branch block, first-degree atrioventricular block, Hashimoto\u0026rsquo;s thyroiditis, hyperhomocysteinemia, and hyperlipidemia, reflecting the multisystem nature of DM1. Cardiac surgical correction for TOF was recommended by surgeons but declined by the patient.\u003c/p\u003e\n\u003cp\u003eThe clinical presentation of this patient was consistent with the adult-onset DM1.\u003csup\u003e4\u003c/sup\u003e Prior to this report, Klompe L et al. described a case of DM1 complicated by TOF in a patient who underwent cardiac surgery, but the diagnosis of DM1 in that study lacked genetic and pathological confirmation.\u003csup\u003e3\u003c/sup\u003e The authors of that study speculated that the coexistence of DM1 and TOF was a coincidental event, a conclusion limited by the lack of definitive DM1 diagnostic evidence. However, our study provides comprehensive evidence confirming both DM1 and TOF, representing the first fully validated case of this rare comorbidity in a DM1 patient. This finding challenges the previous hypothesis of mere coincidence and suggests a potential non-random association between DM1 and congenital conotruncal heart malformations such as TOF. We postulate DMPK, beyond its neuromuscular role, may function in embryonic cardiac conotruncal development; abnormal CTG expansion may disrupt cardiac morphogenesis-related molecules, elevating CHD risk. Alternatively, DM1-associated multisystem developmental perturbations may create an embryonic milieu predisposing to cardiac malformation.\u003c/p\u003e\n\u003cp\u003eThis case expands DM1\u0026rsquo;s cardiac comorbidity spectrum and highlights the need for comprehensive cardiac imaging screening and multidisciplinary follow-up in DM1 patients. Future cohort and molecular studies are warranted to elucidate the DM1-CHD mechanistic link, providing a basis for early screening and personalized management of DM1 patients with cardiac comorbidities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate our cooperative and collaborative patient and his family, and their permission to publish this case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Youth Cultivation Program of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (2025PY125).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKuntawala DH, Vitorino R, Cruz AC, Martins F, Rebelo S. Multisystem Symptoms in Myotonic Dystrophy Type 1: A Management and Therapeutic Perspective. \u003cem\u003eInt J Mol Sci\u003c/em\u003e. 2025; \u003cstrong\u003e26\u003c/strong\u003e .\u003c/li\u003e\n\u003cli\u003eKhan SM, Drury NE, Stickley J, Barron DJ, Brawn WJ, Jones TJ\u003cem\u003e, et al.\u003c/em\u003e Tetralogy of Fallot: morphological variations and implications for surgical repair. \u003cem\u003eEur J Cardiothorac Surg\u003c/em\u003e. 2019; \u003cstrong\u003e56\u003c/strong\u003e: 101-09.\u003c/li\u003e\n\u003cli\u003eKlompe L, Lanc\u0026eacute; M, van der Woerd D, Scohy T, Bogers AJ. Anaesthesiological and ventilatory precautions during cardiac surgery in Steinert\u0026apos;s disease. \u003cem\u003eJ Card Surg\u003c/em\u003e. 2007; \u003cstrong\u003e22\u003c/strong\u003e: 74-75.\u003c/li\u003e\n\u003cli\u003eHartman, J., Patki, T. \u0026amp; Johnson, N. E. Diagnosis and Management of Myotonic Dystrophy Type 1. \u003cem\u003eJAMA\u003c/em\u003e \u003cstrong\u003e331\u003c/strong\u003e, 1227-1228 (2024).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":" Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","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":"No keywords for letters.","lastPublishedDoi":"10.21203/rs.3.rs-9506307/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9506307/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNo abstract for \u003cem\u003eletters\u003c/em\u003e.\u003c/p\u003e","manuscriptTitle":"Myotonic Dystrophy 1 Complicated with Tetralogy of Fallot: A Rare Clinical Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 07:19:18","doi":"10.21203/rs.3.rs-9506307/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":"24dbf50a-1978-4b14-91bf-01d7cc8c8906","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66879109,"name":"Neurology"}],"tags":[],"updatedAt":"2026-04-24T07:19:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 07:19:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9506307","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9506307","identity":"rs-9506307","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}