Heart disease
Catherine Nelson-Piercy in Handbook of Obstetric Medicine, 2020
Marfan syndrome is inherited as an autosomal dominant disorder. Those with cardiac lesions tend to have offspring with cardiac abnormalities. The other features of Marfan syndrome are: Increased heightArm span greater than heightArachnodactylyJoint laxityDepressed sternumHigh arched palateDislocation of the lens
Vascular Disease and Dissection in Pregnancy
Afshan B. Hameed, Diana S. Wolfe in Cardio-Obstetrics, 2020
Marfan syndrome is an autosomal dominant disorder caused by various mutations in the gene (FBN-1 on chromosome 15) that encode for extracellular matrix protein fibrillin I [14,15]. Marfan syndrome has an estimated incidence of 1 in 5000 and involves skeletal, ocular, and cardiovascular systems. Most patients have cardiovascular involvement, and the presence of aortic dilatation confers high risk for morbidity and mortality. Valvular disease, including aortic regurgitation and prolapse of the mitral and tricuspid valves, can lead to arrhythmias and heart failure, and premature rupture of membranes can occur during pregnancy [16,17]. Clinical heterogeneity, even among individuals with the same genetic mutation, can add to the complexity of diagnosis. The original diagnostic criteria, known as the Ghent Nosology, was published in 1996, which was later revised to include many patients who do not have the fibrillin 1 mutation. The diagnosis can be challenging, and a multidisciplinary team should be involved, including clinical genetics. The diagnosis is sometimes only considered after a life-threatening complication occurs during pregnancy [17,18].
Victor McKusick (1921–2008)—Father of Medical Genetics
Krishna Dronamraju in A Century of Geneticists, 2018
As a cardiologist, McKusick encountered many patients with congenital heart problems such as defective valves or deformed aortas. These were sometimes accompanied by other symptoms such as the skeletal and eye abnormalities that characterized a condition known as Marfan syndrome. He thought the various features of this inherited disorder, like those of PJS, were pleiotropic rather than linked and probably due to a mutation-determined defect in one element of connective tissue wherever it occurred in the body. In parallel with his cardiographic studies, he also carried out a comprehensive study of Marfan syndrome and four similar disorders, collecting patients and family histories from his own practice and from many other clinical departments at Johns Hopkins. This work produced his first book, Heritable Disorders of Connective Tissue, first published in 1956.
Pre-implantation genetic testing for Marfan syndrome using mini-sequencing
Published in Journal of Obstetrics and Gynaecology, 2022
Sirivipa Piyamongkol, Krit Makonkawkeyoon, Vorasuk Shotelersuk, Opas Sreshthaputra, Tawiwan Pantasri, Rekwan Sittiwangkul, Theera Tongsong, Wirawit Piyamongkol
The genetic basis of Marfan syndrome is from various mutations within the fibrillin-1 (FBN-1) gene, with over 400 mutations having been reported. About a quarter of MFS are a result of de novo mutations (Robinson et al. 2002). The FBN-1 gene is 230-kb in size, located on 15q21.1 (Lee et al. 1991). The FBN-1 gene is composed of 65 exons, encoding a 2871 amino acid long profibrillin. Profibrillin is then cleaved into FBN-1 by the furin convertase enzyme. Structural defects in fibrillin protein caused decreased vascular strength (Robinson et al. 2006). Some Marfan patients require emergency surgery for aortic root dissection and many need prophylactic aortic root replacement. Aortic surgery is a major surgical procedure with a high intraoperative and postoperative mortality risk even in experienced centres (Fletcher et al. 2020). Permanent paraplegia is one of the most devastating complications with an incidence of 3–5% in elective cases and 19% in emergency cases (Robinson et al. 2006). In addition, re-operative cardiac surgery is not uncommon in Marfan syndrome patients with aortopathy due to dissection of other parts of the aorta (Fletcher et al. 2020).
Double decentred lenses in an eye: a therapeutic dilemma in Marfan syndrome
Published in Clinical and Experimental Optometry, 2020
Wei‐shan Tsai, Yuan‐chieh Lee, Fang‐ling Chang, Ming‐shan He
Marfan syndrome occurs in one in 5,000 children. It is an autosomal dominant disorder that mainly affects the connective tissue. It is caused by the mutation of the fibrillin‐1 gene (FBN1) and subsequently results in elastic fibre malformation.1991 Ectopia lentis was found to be the most common ocular complication, which significantly affects vision.2017 The abnormal fibrillin‐related loose zonules in Marfan syndrome allow the crystalline lens to become more spherical and to decentre relative to the visual axis. Typically, the most common refractive error in Marfan syndrome is high myopia resulting from microspherophakia and longer axial length. The patient in this case received bilateral anterior chamber intraocular lens implantation at another clinic to correct her high myopia. Nevertheless, an anterior chamber intraocular lens implantation in a patient with Marfan syndrome may have a higher risk of intraocular lens decentring due to the unusually deep and large anterior chamber anatomy. Diplopia occurred when the light was bisected simultaneously by the subluxated natural lens and the decentred anterior chamber intraocular lens. Thus, a phenomenon of ‘double decentred lenses in an eye’ was observed in our patient. Therefore anterior chamber intraocular lens implantation alone without removal of the subluxated natural lens may not be sufficient to treat patients with Marfan syndrome.
Ocular Involvement and Treatment Pattern in Korean Patients with Marfan Syndrome: A Population-Based Study
Published in Ophthalmic Epidemiology, 2023
Seongho Kim, Kyungdo Han, Sanghyun Park, EunAh Kim, Su Jeong Song
Marfan syndrome is an autosomal dominant disorder that affects one in every 3000 to 5000 individuals.2,7 Although it is commonly associated with ocular, cardiovascular, and musculoskeletal abnormalities, involvement of the lung, skin, and central nervous system may also occur.8,9 Ectopia lentis was first reported in Marfan syndrome by Börger.10 However, other ocular complications of Marfan syndrome include myopia, flattened cornea, and increased globe size, giving the appearance of pseudoproptosis, miosis, and glaucoma.11,12 Significant ocular involvements are found in approximately 54% of patients,13 which helps to substantiate the diagnosis of Marfan syndrome.
Related Knowledge Centers
- Aorta
- Aortic Aneurysm
- Arachnodactyly
- Mitral Valve Prolapse
- Scoliosis
- Connective Tissue
- Heart
- Genetic Disorder
- Dolichostenomelia
- Hypermobility