#12 |
Marfan syndrome
Image: Gorodenkoff - stock.adobe.com
Introduction and background
First described and named after the French paediatrician Antoine-Bernard Marfan in 1896 [4], the disorder results in variable disease expression with a wide range of clinical manifestations and phenotypical presentations affecting the following systems[1][2][3][5]:
- Cardiovascular: Aortic aneurysm or dissection, valvular prolapse, particularly mitral valve prolapse [3]
- Ocular: Ectopia lentis (dislocated lens)
- Musculoskeletal: Arachnodactyly (abnormally long and thin digits)[1], pectus carinatum or pectus excavatum (chest deformities), hindfoot valgus, dolichostenomelia (disproportionately long limbs relative to trunk length) kyphoscoliosis (spinal deformity)
- Respiratory: Cystic lung disease, spontaneous pneumothorax
- Neurological: Dural ectasia, headaches, lower back pain, bladder or bowel weakness
- Skin: Skin stria
The typical pathognomic phenotype of Marfan syndrome includes disproportionately long limbs (dolichostenomelia), scoliosis, potentially life-threatening aortic artery pathology, specifically aortic aneurysms or dissections, and the ocular manifestation of lens dislocation (ectopia lentis).[3][5]
Marfan syndrome commonly follows an autosomal dominant inheritance pattern. Pathogenesis involves mutations of the FBN1 gene on chromosome 15, the gene responsible for encoding fibrillin, a connective tissue protein. This mutation ultimately results in the systemic connective tissue disorder. While 75% of cases are shown to be inherited, about 25% arise de novo from new mutations in the FBN1 gene.[3]
Diagnosis
The diagnostic process is usually prompted by family history or clinical suspicion, based on clinical presentation suggestive of Marfan syndrome as a diagnosis. Diagnosis is based on a combination of clinical evaluation, imaging studies, and genetic testing. Key clinical assessments include a comprehensive medical history, physical examination, echocardiography or cardiac MRI and ophthalmological evaluation, in order to elicit the pathognomonic systemic features of Marfan syndrome. Genetic testing for the FBN1 mutation is not routinely indicated, but rather employed where results can inform management decisions, facilitate familial screening, or assist with differentiating from other differential diagnoses.
The results from these investigations form part of the assessment using the revised 2010 Ghent criteria. The core diagnostic features of the 2010 Ghent criteria are the assessment of aortic root dilation or dissection, dislocation of the lens of the eye, and a systemic score evaluating other typical skeletal, ocular and dermatological features, stratified either with or without a family history of Marfan syndrome. Accurate diagnosis using the 2010 revised Ghent score facilitates timely intervention, with the goal of preventing life-threatening complications and improving overall quality of life.[1][3][5][7].
Treatment and management
The management of Marfan syndrome incorporates prevention and management of complications of the affected body systems, usually assessed with annual monitoring. Key strategies include surveillance and treatment of cardiovascular manifestations. Monitoring of aortic manifestations typical of Marfan syndrome is done by means of echocardiography, CT or MRI scans. Beta blockers or angiotensin II receptor blockers are commonly used in drug therapy to control blood pressure and reduce the risk of life-threatening complications, such as aortic aneurysm rupture or aortic dissection.
Additionally, treatment strategies often include surgical interventions, such as aortic root replacement or mitral valve repair. For non-cardiovascular complications, examples of management options based on presentation are ophthalmological evaluation, conservative or surgical management of musculoskeletal or respiratory manifestations, and close monitoring during pregnancy. Genetic counselling and screening are often recommended for family members.[1][3][5][9].
An overview of the 2010 Revised Ghent Nosology for Marfan syndrome can be accessed on the Marfan Foundation website: https://marfan.org/dx/rules/ [8]
Underwriting considerations
Marfan syndrome presents significant challenges in underwriting due to its potential for poor morbidity and mortality related outcomes, as well as the variable presentation of the disease. A thorough assessment of systemic involvement, such as cardiovascular, skeletal, and ocular complications, is essential. Additionally, country-specific regulations and industry standards regarding genetic testing and its results must be carefully considered. However, advances in medical treatment and management have improved the prognosis for individuals with Marfan syndrome, making it possible to assess this once critical condition more effectively during the underwriting process.
Author
Dr Krishnaveni Govender
Medical Doctor
Hannover Re South Africa Limited
January 2025
References
- Prashanth Inna, MBBS, MS, DNB; Chief Editor: Jeffrey D Thomson, MD. Marfan Syndrome (MFS). Updated: Jul 01, 2024. Available from: https://emedicine.medscape.com/article/1258926-overview. Viewed on 15 November 2024.
- Yukiko Isekame, Sabiha Gati, Jose Antonio Aragon-Martin, Rachel Bastiaenen, Sreenivasa Rao Kondapally Seshasai, Anne Child. Cardiovascular Management of Adults with Marfan Syndrome. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6159454/. Viewed on 18 November 2024.
- Michael J Wright, MBChB, MSc, Heidi M Connolly, MD, FACC, FASE. Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders. Available from: https://www.uptodate.com/contents/genetics-clinical-features-and-diagnosis-of-marfan-syndrome-and-related-disorders. Viewed on 18 November 2024.
- Aline Verstraeten, Maaike Alaerts, Lut Van Laer, Bart Loeys. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/humu.22977#:~:text=In%201896%2C%20the%20French%20pediatrician,)%20(Marfan%2C%201896). Viewed on 21 November 2024.
- Frank Pessler, MD, PhD. Marfan Syndrome. Available from: https://www.msdmanuals.com/professional/pediatrics/connective-tissue-disorders-in-children/marfan-syndrome. Viewed on 21 November 2024.
- Irim Salik, Prashanth Rawla. Marfan Syndrome. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537339/. Viewed on 21 November 2024.
- Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan Syndrome. Available from: https://www.uptodate.com/contents/genetics-clinical-features-and-diagnosis-of-marfan-syndrome-and-related-disorders/abstract/17. Viewed on 22 November 2024.
- The Marfan Foundation . Summary of Diagnostic. Available from: https://marfan.org/dx/rules/. Viewed on 21 November 2024.
- Michael J Wright, MBChB, MScHeidi M Connolly, MD, FACC, FASE. Management of Marfan syndrome and related disorders. Available from: https://www.uptodate.com/contents/management-of-marfan-syndrome-and-related-disorders. Viewed on 15 and 22 November 2024.
If you need further information or would like to send us feedback, please feel free to get in touch.
The information provided in this document does in no way whatsoever constitute legal, accounting, tax or other professional advice. While Hannover Rück SE has endeavoured to include in this document information it believes to be reliable, complete and up-to-date, the company does not make any representation or warranty, express or implied, as to the accuracy, completeness or updated status of such information. Therefore, in no case whatsoever will Hannover Rück SE and its affiliated companies or directors, officers or employees be liable to anyone for any decision made or action taken in conjunction with the information in this document or for any related damages.
Hannover Re is the registered service mark of Hannover Rück SE.
Hannover Rück SE © 2024