Neuropsychiatric complications in a patient with Marfan syndrome

BackgroundMarfan syndrome (MFS) is an autosomal dominant disorder of fibrillin-1 gene mutations, with the involvement of cardiovascular, skeletal, and ocular systems. In addition to physical abnormalities, MFS patients are also found to be susceptible to schizophrenia and other psychiatric conditions.ObjectivesAwareness of the association between MFS and psychiatric conditions would improve the clinical management of MFS patients to reduce the risk or even to prevent the development of psychiatric complications in MFS patients.MethodsHere, we describe a male MFS patient who manifested incoherent speech and impaired cognitive and social function at the age of 40 years.Results and conclusionHis mental dysfunction could be attributed to his bilateral cerebral infarction, which is a neurovascular complication associated with MFS.

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Genetic analysis of the contribution of LTBP-3 to thoracic aneurysm in Marfan syndrome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1507652112 ◽

2015 ◽

Vol 112 (45) ◽

pp. 14012-14017 ◽

Cited By ~ 21

Author(s):

Lior Zilberberg ◽

Colin K. L. Phoon ◽

Ian Robertson ◽

Branka Dabovic ◽

Francesco Ramirez ◽

...

Keyword(s):

Aortic Aneurysm ◽

Marfan Syndrome ◽

Autosomal Dominant ◽

Aortic Disease ◽

Elastic Fibers ◽

Thoracic Aneurysm ◽

Tgfβ Signaling ◽

Autosomal Dominant Disorder ◽

Present Evidence ◽

Fibrillin 1

Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, caused by mutations of the microfibrillar protein fibrillin-1, that predisposes affected individuals to aortic aneurysm and rupture and is associated with increased TGFβ signaling. TGFβ is secreted from cells as a latent complex consisting of TGFβ, the TGFβ propeptide, and a molecule of latent TGFβ binding protein (LTBP). Improper extracellular localization of the latent complex can alter active TGFβ levels, and has been hypothesized as an explanation for enhanced TGFβ signaling observed in MFS. We previously reported the absence of LTBP-3 in matrices lacking fibrillin-1, suggesting that perturbed TGFβ signaling in MFS might be due to defective interaction of latent TGFβ complexes containing LTBP-3 with mutant fibrillin-1 microfibrils. To test this hypothesis, we genetically suppressed Ltbp3 expression in a mouse model of progressively severe MFS. Here, we present evidence that MFS mice lacking LTBP-3 have improved survival, essentially no aneurysms, reduced disruption and fragmentation of medial elastic fibers, and decreased Smad2/3 and Erk1/2 activation in their aortas. These data suggest that, in MFS, improper localization of latent TGFβ complexes composed of LTBP-3 and TGFβ contributes to aortic disease progression.

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Early-Onset Marfan Syndrome: A Case Series

Journal of Pediatric Genetics ◽

10.1055/s-0038-1675338 ◽

2018 ◽

Vol 08 (02) ◽

pp. 086-090

Author(s):

Mohanageetha Ardhanari ◽

Deborah Barbouth ◽

Sethuraman Swaminathan

Keyword(s):

Heart Failure ◽

Connective Tissue ◽

Marfan Syndrome ◽

Early Onset ◽

Autosomal Dominant ◽

Case Series ◽

Autosomal Dominant Disorder ◽

Fibrillin 1 ◽

Valvular Insufficiency ◽

Multisystem Manifestations

AbstractMutations in fibrillin 1 cause Marfan syndrome (MFS), an autosomal dominant disorder of the connective tissue, with multisystem manifestations. In early-onset MFS, the physical characteristics are expressed much earlier than the classical MFS. Those affected by this form generally have their mutations restricted to the gene “hotspot” region of exons 24 to 32. Historically, affected individuals usually die within the first few years of life due to heart failure secondary to severe valvular insufficiency. We report three patients with early-onset MFS, whose clinical evolution has been remarkably positive, when compared with other reported cases in the literature.

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Identification of fibrillin-1 gene mutations in Marfan syndrome by high-resolution melting analysis

Analytical Biochemistry ◽

10.1016/j.ab.2009.03.032 ◽

2009 ◽

Vol 389 (2) ◽

pp. 102-106 ◽

Cited By ~ 11

Author(s):

Chia-Cheng Hung ◽

Shin-Yu Lin ◽

Chien-Nan Lee ◽

Hui-Yu Cheng ◽

Chiou-Ya Lin ◽

...

Keyword(s):

High Resolution ◽

Marfan Syndrome ◽

High Resolution Melting ◽

Gene Mutations ◽

High Resolution Melting Analysis ◽

Fibrillin 1 ◽

Melting Analysis

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Marfan Syndrome: A Case Report

Case Reports in Dentistry ◽

10.1155/2012/595343 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Rajendran Ganesh ◽

Rajendran Vijayakumar ◽

Haridoss Selvakumar

Keyword(s):

Stainless Steel ◽

Case Report ◽

Connective Tissue ◽

Blood Vessel ◽

Marfan Syndrome ◽

Autosomal Dominant ◽

The Body ◽

Tissue Protein ◽

Fibrillin 1 ◽

Systemic Disorder

Marfan syndrome is an autosomal dominant systemic disorder of the connective tissue. Children affected by the Marfan syndrome carry a mutation in one of their two copies of the gene that encodes the connective tissue protein fibrillin-1. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the rest of the body. A case report of Marfan syndrome has been reported with oral features. The dental problems of the child were treated under general anesthesia and a one-month review showed intact stainless steel crowns' restorations and no signs of secondary caries.

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Abstract 11621: Fibrillin-1 Gene Mutations in Left Ventricular Non-Compaction Cardiomyopathy

Circulation ◽

10.1161/circ.130.suppl_2.11621 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

John J Parent ◽

Jeffrey A Towbin ◽

John L Jefferies

Keyword(s):

Extracellular Matrix ◽

Gene Mutation ◽

Marfan Syndrome ◽

Gene Mutations ◽

Left Ventricular ◽

Current Evidence ◽

Causative Gene ◽

Fbn1 Gene ◽

Gene Testing ◽

Fibrillin 1

Introduction: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare and unique cardiomyopathy. Its presentation can range from a benign phenotype to overt heart failure and sudden cardiac death. The genetics of LVNC are not completely understood and current genetic testing has a yield of about 30% in identifying a causative gene mutation. We present a series of patients with LVNC and fibrillin-1 (FBN1) gene mutations. Hypothesis: We hypothesize that FBN1 gene mutations can lead to LVNC by way of its role in the myocardial extracellular matrix during cardiac development. Methods: A retrospective review of all patients with LVNC at our institution was performed for purposes of another investigation. The process unexpectedly identified patients with LVNC and FBN1 gene mutations, as well as LVNC and Marfan syndrome. Results: Approximately 150 patients are followed in our clinic with LVNC. We screened this population and found 51 patients on medical therapy for reduced function. We retrospectively reviewed gene testing in these 51 patients, when available, and identified 5 patients (10%) with an FBN1 gene mutation. All 5 patients had a dilated LVNC phenotype and previous or current evidence of left ventricular dysfunction. Syndrome breakdown as follows: 3 with Marfan, 1 with Shprintzen-Goldberg, and 1 with no identifiable syndrome. Dilated cardiomyopathy/LVNC gene testing was performed in 3 patients; 2 had disease causing myosin heavy chain 7 gene defects and 1 had no defects. Conclusions: The role of FBN1 in the human myocardium is not completely understood but it is expressed in the developing fetal heart and is a component of the myocardial extracellular matrix. Although causation has not been proven by our report, it certainly raises interest in a mechanistic relationship between LVNC and FBN1 given the increased prevalence of Marfan syndrome and probable increased prevalence of FBN1 gene mutations in this cohort of LVNC patients in light of FBN1.

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Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome

BMC Medical Genetics ◽

10.1186/1471-2350-15-23 ◽

2014 ◽

Vol 15 (1) ◽

Cited By ~ 55

Author(s):

Guglielmina Pepe ◽

Stefano Nistri ◽

Betti Giusti ◽

Elena Sticchi ◽

Monica Attanasio ◽

...

Keyword(s):

Aortic Valve ◽

Marfan Syndrome ◽

Bicuspid Aortic Valve ◽

Gene Mutations ◽

Fibrillin 1

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Simultaneous Occurrence of Duane Retraction Syndrome with Marfan Syndrome

Case Reports in Ophthalmological Medicine ◽

10.1155/2011/784259 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Mihir Kothari ◽

Florence Manurung ◽

Bhavesh Mithiya

Keyword(s):

Case Report ◽

Connective Tissue ◽

Marfan Syndrome ◽

Autosomal Dominant ◽

Simultaneous Occurrence ◽

Autosomal Dominant Disorder ◽

First Case ◽

Retraction Syndrome ◽

Congenital Cranial Dysinnervation Disorder ◽

Duane Retraction Syndrome

Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, while Duane retraction syndrome (DRS) is a congenital cranial dysinnervation disorder (CCDD) which can be transmitted as autosomal dominant disorder in 5–10% of patients. In this paper, we present an 8-year-old girl who presented with left eye DRS and bilateral subluxation of the lens associated with MFS in absence of familial involvement. To our knowledge this is the first case report of DRS with MFS. The occurrence of these syndromes together is very rare and appears to be coincidental.

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Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: Do we need genetics for clinical decisions?

VASA ◽

10.1024/0301-1526/a000002 ◽

2010 ◽

Vol 39 (1) ◽

pp. 17-32 ◽

Cited By ~ 14

Author(s):

von Kodolitsch ◽

Rybczynski ◽

Bernhardt ◽

Mir ◽

Treede ◽

...

Keyword(s):

Marfan Syndrome ◽

Autosomal Dominant ◽

Aortic Disease ◽

Aortic Aneurysms ◽

Clinical Implications ◽

Thoracic Aortic Disease ◽

Gene Coding ◽

Autosomal Dominant Fashion ◽

Fibrillin 1 ◽

Work Up

Marfan syndrome (MFS) is a disorder of the connective tissue that is inherited in an autosomal dominant fashion and that is classically caused by mutations in the gene coding for fibrillin-1, FBN1. The high mortality of untreated MFS results almost exclusively from aortic complications such as aortic dissection and rupture. However, more than half of patients with Marfan-like features do not have MFS, but have other diseases including inherited aortic aneurysms and dissections (TAAD). We elucidate the increasing spectrum of syndromes associated with Marfan-like features and discuss the clinical implications of these diseases. We performed a systematic review to tabulate all known inherited diseases and syndromes carrying a risk for thoracic aortic disease. We discuss evidence that different syndromes with different causative genes and mutations have different prognoses and profiles of cardiovascular manifestations. We conclude that future decisions for optimized management of patients with inherited TAAD require a comprehensive clinical and genetic work-up.

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Neonatal Marfan Syndrome

American Journal of Perinatology ◽

10.1055/s-0039-1691770 ◽

2019 ◽

Vol 36 (S 02) ◽

pp. S74-S76 ◽

Cited By ~ 1

Author(s):

Eleonora Tognato ◽

Anna Perona ◽

Angela Aronica ◽

Antonella Bertola ◽

Lina Cimminelli ◽

...

Keyword(s):

Marfan Syndrome ◽

Rare Condition ◽

Ocular Involvement ◽

Autosomal Dominant Disorder ◽

Adequate Treatment ◽

Pathogenic Variants ◽

Fibrillin 1 ◽

Birth Characteristics ◽

Neonatal Marfan Syndrome ◽

Male Neonate

Abstract Objective The Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue resulting from pathogenic variants of the fibrillin-1 gene (FBN1) with skeletal, cardiac, and ocular involvement. Study Design We report on a full-term male neonate, who showed at birth characteristics and dysmorphisms suggestive of nMFS, combined with the detection of severe cardiovascular disease. A multidisciplinary team made up of neonatologists and pediatricians, cardiologists, geneticists, ophtalmologists, physiatrists and physioterapists was formed to manage this patient. Results and Conclusion Early diagnosis of this rare condition is critical for adequate treatment and specific follow-up, and impacts significantly on prognosis.

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Marfan Syndrome with CRHD

Indian Journal of Cardiovascular Disease in Women WINCARS ◽

10.1055/s-0040-1708580 ◽

2020 ◽

Vol 5 (04) ◽

pp. 322-326

Author(s):

Shahood Ajaz Kakroo

Keyword(s):

Marfan Syndrome ◽

Autosomal Dominant ◽

Similar Case ◽

Extensive Search ◽

Organ Systems ◽

The Family ◽

Fibrillin 1 ◽

History Of ◽

Mode Of Inheritance ◽

Rheumatic Heart

AbstractMarfan syndrome (MFS) is an inheritable disorder caused by mutation of fibrillin-1 gene. It is the most common disorder among disorders of connective tissue. Its mode of inheritance is autosomal dominant. The reported prevalence of this disorder is one in three thousand (3000) to five (5000) thousand individuals. It presents with varied manifestation and different range of severity. The organ systems most commonly affected by this disorder include eyes, cardiovascular system, and musculoskeletal system.The other systems which may be affected include respiratory system, skin, and central nervous system. It is diagnosed with the help of revised Ghent score which includes a set of various diagnostic criteria which need to be fulfilled. MFS in this patient was diagnosed after the fulfillment of the revised Ghent score criteria, which included a positive history of MFS in the family and a systemic score of 8.In this case report, we are reporting a case of MFS which is unusual and remarkable in the sense that it is associated with chronic rheumatic heart disease (CRHD), and not the cardiovascular features which are usually present in cases of MFS. We tried to find a similar case if ever reported previously and, after extensive search, we could find only few cases13 14 15 of MFS which were associated with CRHD.

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