RARE DISEASE
Marfan syndrome
Marfan syndrome
Marfan syndrome
Synonyms: MFS
Synonyms: MFS
Synonyms: MFS
Drug discovery
3
drugs
With orphan designations
Overview
Marfan syndrome is an autosomal dominant connective tissue disorder caused by fibrillin-1 gene mutations, leading to cardiovascular, skeletal, ocular, and vascular manifestations. Key features include aortic root dilation, lens dislocation, and disproportionate skeletal growth. Complications such as aortic dissection, mitral valve prolapse, and retinal detachment drive morbidity and mortality. Management involves beta-blockers, angiotensin receptor blockers, prophylactic aortic surgery (at 4.5–5 cm), and multidisciplinary monitoring [1][6][11].
Therapies
Pharmacologic: Beta-blockers (atenolol) or ARBs (losartan) to reduce aortic stress [3][10][16].
Surgical: Prophylactic aortic root replacement at 4.5–5 cm; valve-sparing techniques preferred [6][11][17].
Multidisciplinary care: Annual cardiac imaging, ophthalmologic exams, and orthopedic/physiotherapy interventions [8][16].
Categories: rare bone diseases, rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare ophthalmic disorders, rare surgical thoracic diseases, rare systemic and rheumatological diseases
Research Papers
1,626 drug discovery papers related to Marfan syndrome, with 3 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,626 drug discovery papers related to Marfan syndrome, with 3 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-04 | Marfan Syndrome: Molecular Basis, Clinical Spectrum, Diagnosis, and Management- A Comprehensive Review
Marfan syndrome (MFS) is a hereditary connective tissue disorder primarily caused by mutations in the FBN1 gene, leading to abnormalities in extracellular microfibril formation and dysregulation of transforming growth factor-beta (TGF-β) signaling. The disorder exhibits autosomal dominant inheritance and presents with significant clinical variability, affecting the cardiovascular, skeletal, and ocular systems. Among these, cardiovascular complications such as aortic root dilation, aneurysm, and dissection represent the most life-threatening manifestations. Advances in diagnostic approaches, particularly the revised Ghent criteria, have improved diagnostic accuracy by integrating clinical features, imaging findings, and genetic testing. Imaging modalities such as echocardiography, magnetic resonance imaging, and computed tomography play a critical role in early detection and monitoring of disease progression. Genetic testing further enhances diagnostic precision, especially in atypical cases. Management strategies focus on preventing complications and improving survival. Pharmacological treatments, including beta-blockers and angiotensin receptor blockers, reduce hemodynamic stress and modulate TGF-β signaling. Surgical interventions, particularly prophylactic aortic root replacement, are essential in high-risk patients. A multidisciplinary approach involving cardiology, genetics, ophthalmology, and orthopedics is crucial for optimal patient care. Emerging diagnostic tools such as next-generation sequencing and biomarker-based assessments, along with novel therapeutic strategies including gene therapy and targeted molecular treatments, hold promise for future disease management. Continued research into the molecular mechanisms of MFS is essential to transition from symptomatic treatment to disease-modifying therapies and to further improve patient outcomes.
2026-06-30 | Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses
Heritable thoracic aortic diseases (HTADs) comprise a genetically heterogeneous group of disorders predisposing patients to thoracic aortic aneurysm and dissection, yet current medical therapies remain limited to slowing disease progression rather than preventing aortic wall failure. Although pathogenic variants affect diverse genes encoding extracellular matrix (ECM) components, smooth muscle contractile proteins, and signaling molecules, these defects converge on disruption of the mechanobiological systems that maintain aortic wall integrity. The thoracic aorta functions as a mechanically integrated tissue in which endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells and ECM continuously sense and respond to pulsatile biomechanical forces. Genetic perturbations affecting ECM architecture, contractile force generation, or growth factor signaling alter force transmission across this multicellular network, leading to maladaptive mechanotransduction, cellular phenotypic modulation, and progressive aneurysm formation. Using Marfan syndrome as a paradigmatic ECM-driven aortic disease, this review synthesizes current understanding of how altered biomechanics, biochemical signaling and immune responses reshape intercellular communication and activate disease-associated signaling pathways, including dysregulated TGF-β, nitric oxide, angiotensin receptor, calcium-dependent, and metabolic signaling. We highlight how single-cell transcriptomic analyses have elaborated changes in different cell-level functions including, ECM degradation, iron homeostasis, circadian/stress responses. Changes in iron metabolism in different cell types in the aorta suggest possible coordinated metabolic changes in aneurysm progression. These mechanistic insights enable the identification of cell-type–specific pathogenic programs and therapeutic discovery through systems-level approaches. We highlight the translational opportunities and challenges emerging from mouse models and human studies, emphasizing that therapeutic efficacy depends not only on pathway selection but also on disease stage, cellular context, and timing of intervention. Together, these findings support a model in which HTAD progression reflects dynamic, multicellular failure of mechanobiological homeostasis and provide a framework for the development of more precise, mechanism-based therapies.
2026-06-30 | Multidisciplinary management of Grade III circumferential mixed hemorrhoids in a patient with Marfan syndrome receiving long-term anticoagulation: a case report.
Management of advanced hemorrhoidal disease in patients with Marfan syndrome (MFS) who require lifelong anticoagulation is clinically complex because perioperative care must balance prosthetic valve thrombosis against postoperative anorectal bleeding. We report the case of a 33-year-old male with MFS, status post-aortic dissection repair (Sun's procedure and Bentall operation) on continuous warfarin therapy, who presented with persistent Grade III circumferential mixed hemorrhoids that had not responded adequately to prior conservative outpatient management. Physical examination confirmed characteristic MFS musculoskeletal signs and severe hemorrhoidal prolapse. A structured multidisciplinary team (MDT) pathway involving colorectal surgery, cardiovascular medicine, vascular surgery, anesthesia, pharmacy, and nutrition was used to individualize perioperative management. After cardiology consultation, and based on the patient's high thromboembolic risk, preoperative warfarin interruption was shortened to 3 days with enoxaparin bridging, and the INR decreased to 1.01 on the day before surgery. Rubber band ligation was avoided because of concern for delayed bleeding after sloughing in an anticoagulated patient. Because the disease involved circumferential mixed hemorrhoids with a prominent external component and prolapse, repeated sclerotherapy alone was considered unlikely to provide adequate definitive control. The patient therefore underwent external dissection and internal ligation combined with liquid polidocanol injection sclerotherapy, with minimal intraoperative blood loss. Postoperatively, a 25-day inpatient observation period enabled close INR titration during warfarin reinitiation, controlled bowel management, staged low-residue enteral nutrition, avoidance of rectal suppositories, and direct monitoring for delayed bleeding. Following minor self-limiting hematochezia, the patient was discharged with an INR of 1.8 as a pragmatic compromise between bleeding and thrombotic risks. At 41 months of follow-up, the wounds remained well healed, with no recurrent prolapse or severe hemorrhagic complications. This case suggests that surgical intervention for advanced hemorrhoids in anticoagulated MFS patients may be feasible when embedded within a structured, individualized multidisciplinary pathway. The anticoagulation, nutritional, and inpatient-monitoring strategies described here should be interpreted as patient-specific measures requiring further validation.
2026-07-04 | Marfan Syndrome: Molecular Basis, Clinical Spectrum, Diagnosis, and Management- A Comprehensive Review
Marfan syndrome (MFS) is a hereditary connective tissue disorder primarily caused by mutations in the FBN1 gene, leading to abnormalities in extracellular microfibril formation and dysregulation of transforming growth factor-beta (TGF-β) signaling. The disorder exhibits autosomal dominant inheritance and presents with significant clinical variability, affecting the cardiovascular, skeletal, and ocular systems. Among these, cardiovascular complications such as aortic root dilation, aneurysm, and dissection represent the most life-threatening manifestations. Advances in diagnostic approaches, particularly the revised Ghent criteria, have improved diagnostic accuracy by integrating clinical features, imaging findings, and genetic testing. Imaging modalities such as echocardiography, magnetic resonance imaging, and computed tomography play a critical role in early detection and monitoring of disease progression. Genetic testing further enhances diagnostic precision, especially in atypical cases. Management strategies focus on preventing complications and improving survival. Pharmacological treatments, including beta-blockers and angiotensin receptor blockers, reduce hemodynamic stress and modulate TGF-β signaling. Surgical interventions, particularly prophylactic aortic root replacement, are essential in high-risk patients. A multidisciplinary approach involving cardiology, genetics, ophthalmology, and orthopedics is crucial for optimal patient care. Emerging diagnostic tools such as next-generation sequencing and biomarker-based assessments, along with novel therapeutic strategies including gene therapy and targeted molecular treatments, hold promise for future disease management. Continued research into the molecular mechanisms of MFS is essential to transition from symptomatic treatment to disease-modifying therapies and to further improve patient outcomes.
2026-06-30 | Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses
Heritable thoracic aortic diseases (HTADs) comprise a genetically heterogeneous group of disorders predisposing patients to thoracic aortic aneurysm and dissection, yet current medical therapies remain limited to slowing disease progression rather than preventing aortic wall failure. Although pathogenic variants affect diverse genes encoding extracellular matrix (ECM) components, smooth muscle contractile proteins, and signaling molecules, these defects converge on disruption of the mechanobiological systems that maintain aortic wall integrity. The thoracic aorta functions as a mechanically integrated tissue in which endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells and ECM continuously sense and respond to pulsatile biomechanical forces. Genetic perturbations affecting ECM architecture, contractile force generation, or growth factor signaling alter force transmission across this multicellular network, leading to maladaptive mechanotransduction, cellular phenotypic modulation, and progressive aneurysm formation. Using Marfan syndrome as a paradigmatic ECM-driven aortic disease, this review synthesizes current understanding of how altered biomechanics, biochemical signaling and immune responses reshape intercellular communication and activate disease-associated signaling pathways, including dysregulated TGF-β, nitric oxide, angiotensin receptor, calcium-dependent, and metabolic signaling. We highlight how single-cell transcriptomic analyses have elaborated changes in different cell-level functions including, ECM degradation, iron homeostasis, circadian/stress responses. Changes in iron metabolism in different cell types in the aorta suggest possible coordinated metabolic changes in aneurysm progression. These mechanistic insights enable the identification of cell-type–specific pathogenic programs and therapeutic discovery through systems-level approaches. We highlight the translational opportunities and challenges emerging from mouse models and human studies, emphasizing that therapeutic efficacy depends not only on pathway selection but also on disease stage, cellular context, and timing of intervention. Together, these findings support a model in which HTAD progression reflects dynamic, multicellular failure of mechanobiological homeostasis and provide a framework for the development of more precise, mechanism-based therapies.
2026-06-30 | Multidisciplinary management of Grade III circumferential mixed hemorrhoids in a patient with Marfan syndrome receiving long-term anticoagulation: a case report.
Management of advanced hemorrhoidal disease in patients with Marfan syndrome (MFS) who require lifelong anticoagulation is clinically complex because perioperative care must balance prosthetic valve thrombosis against postoperative anorectal bleeding. We report the case of a 33-year-old male with MFS, status post-aortic dissection repair (Sun's procedure and Bentall operation) on continuous warfarin therapy, who presented with persistent Grade III circumferential mixed hemorrhoids that had not responded adequately to prior conservative outpatient management. Physical examination confirmed characteristic MFS musculoskeletal signs and severe hemorrhoidal prolapse. A structured multidisciplinary team (MDT) pathway involving colorectal surgery, cardiovascular medicine, vascular surgery, anesthesia, pharmacy, and nutrition was used to individualize perioperative management. After cardiology consultation, and based on the patient's high thromboembolic risk, preoperative warfarin interruption was shortened to 3 days with enoxaparin bridging, and the INR decreased to 1.01 on the day before surgery. Rubber band ligation was avoided because of concern for delayed bleeding after sloughing in an anticoagulated patient. Because the disease involved circumferential mixed hemorrhoids with a prominent external component and prolapse, repeated sclerotherapy alone was considered unlikely to provide adequate definitive control. The patient therefore underwent external dissection and internal ligation combined with liquid polidocanol injection sclerotherapy, with minimal intraoperative blood loss. Postoperatively, a 25-day inpatient observation period enabled close INR titration during warfarin reinitiation, controlled bowel management, staged low-residue enteral nutrition, avoidance of rectal suppositories, and direct monitoring for delayed bleeding. Following minor self-limiting hematochezia, the patient was discharged with an INR of 1.8 as a pragmatic compromise between bleeding and thrombotic risks. At 41 months of follow-up, the wounds remained well healed, with no recurrent prolapse or severe hemorrhagic complications. This case suggests that surgical intervention for advanced hemorrhoids in anticoagulated MFS patients may be feasible when embedded within a structured, individualized multidisciplinary pathway. The anticoagulation, nutritional, and inpatient-monitoring strategies described here should be interpreted as patient-specific measures requiring further validation.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Marfan syndrome.
3 orphan drug designations for Marfan syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
enzastaurin | small molecules | FDA | 2025-04-14 | — | Aytu BioPharma, Inc. |
Allopurinol | small molecules | EMA | 2025-03-25 | — | Consorcio Centro De Investigacion Biomedica En Red |
losartan | small molecules | FDA | 2011-12-12 | — | National Marfan Foundation |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.