Marfan syndrome is an inherited (genetic) disease (autosomal dominant) caused by a defect (misfolding) in the protein fibrillin-1, which is encoded by the gene FBN1 on chromosome 15. Thus, Marfan's syndrome is a congenital, genetic condition that differs from the inflammatory-like, systemic autoimmune connective tissue diseases. About 25% are spontaneous mutations without family disposition (Big Norwegian Leksikon, A Heiberg 2009). Along with a vascular form (which attacks blood vessels) of Ehlers-Danlos syndrome, Loeys-Dietz syndrome og hereditary thoracic aortic aneurysm (HTAD), the disease is included among the hereditary "Marfan-like" diseases.
The number of new cases each year (incidence) of Marfan's syndrome is 2-3/10000. Assuming all are recognized was equivalent to 1/9802 newborns in a Scottish study (Gray JR, 1994). The incidence in the population (prevalence) is estimated at: one in 20.000 people (approx. 500 in Norway). Marfan's disease is thus defined as a rare disease (fewer than 1 per 2.000 people according to the Norwegian Ministry of Health and Welfare). Nevertheless, it is considered one of the most common inherited diseases that attack the musculoskeletal system.
The skeletal system
- Conspicuously large body height (reference: Erkula G, 2002).
- Sideways curved back (scoliosis), long, arms and legs (dolichostemomeli) with long fingers and toes (arachnodaktyli) in relation to the length of the body is common (reference: Lindsey J, 1998).
- Breast bone deformities as bird breasts (pectus carniatum) and hypermobile (hypermobility) joints are also often seen (reference: Kaissi AA, 2013).
- There are often severe visual disturbances with nearsightedness (myopia) and Astigmatism (astigmatism). Lens subluxation (ectoptic lens) is demonstrated by an ophthalmologist. Someone is developing glaucoma (glaucoma) or early cataract (cataract) (reference: Zech JC, 2020).
The heart and blood vessels
- The most serious complications, which can be life-threatening, include irregular heart rhythm, heart valve leakage, enlarged diameter of the main artery (aortic aneurysm), aortic dissection (damage and leakage in the blood vessel wall)f(Rybczynski M, 2010).
- Special attention in pregnancy is important
Skin. Stretch marks (stretch marks) is due to hypermobile connective tissue.
Marfan's syndrome is suspected on the basis of symptoms and examination findings (see above).
Also often used criteria for diagnosis (2010 Ghent) which distinguishes between those who have Marfan's disease in their immediate family and those without hereditary disposition:
Without hereditary disposition:
- Aortic root enlarged (Z-score ≥2) and ectopic lens
- Aortic root expanded (Z-score ≥2) and FBN1 mutation (gene test)
- Aortic root dilated (Z-score ≥2) and systemic scoring *> 7 points (special scoring system *)
- Ectopic lens and FBN1 mutation with known aortic infection
With family with Marfan's disease:
- Ectoptic lens
- Systemic score * Aortic root expanded ≥7
- Aortic root dilated (Z-score ≥2)
* Pectus carniatum = 2 (pes excavatum or asymmetric = 1), Malleol deformity (ankle) = 2 (flat foot = 1), Dural ectasi = 2, Protrusio acetabuli = 2, Dys proportional arm length = 1, Scoliosis or kyphosis = 1, Reduced Elbow Extension = 1, Facial Skeleton Changes = 1, Striae in Skin = 1, Myopy = 1, Mitral Prolapse = 1.
Old criteria: Major criteria (at least 4):
- Reduced proportion of upper body / lower body ratio (0,85 vs 0,93 in normal)
- Arachnodactyli (fingers, toes), positive thumb-wrist test)
- Scoliosis more than 20 degrees or spondylolistesis
- Medial malleol misalignment giving pes planus (plate foot)
- Reduced extension of elbows (
- Pectum carniatum (bird breast) (Differential Diagnosis: Morquio syndrome, Noonan syndrome, Trisomi 18, Trisomi 21, Homocystinuria, Osteogenesis imperfecta, Multiple lentigine syndrome, and Sly syndrome)
- Pectus excavatum (funnel chest) that requires surgery
- Protrusio Acetabuli (Differential diagnoses: Paget's syndrome, rheumatoid arthritis, ankylosing spondylitis, osteomalacia)
Genetics / Heredity
A spontaneous mutation is often present (25%), without a corresponding disease being seen in the immediate family. Mutation in the gene FBN1 can be detected in approx. 85% with clinically definite Marfan's disease (reference: Store Norske Leksikon, Heiberg A, 2009). Sample can be sent to Oslo University Hospital, Ullevål. More about genetic tests on the genetics portal.
There is still no treatment that cures Marfan's syndrome. But the prognosis has improved a lot over the last ten years. This is related to the use of regular medical follow-up that includes cardiac specialist (cardiologist) checks, blood vessel tests to exclude or follow up aneurysms and treatment of pneumothorax.
Similar diseases / differential diagnoses
One must not forget that many healthy people have several of the symptoms without being attacked by the disease. If there is a strong suspicion of Marfan's disease, the investigation may consider:
- Hereditary thoracic aortic aneurysm (HTAD)
- Ehlers-Danlos syndrome
- Ectopic lens syndrome (ELS), familial thoracic aortic aneurysm and dissection syndrome (FTAAD/FTAA).
- Hypermobility syndrome
- Loeys-Dietz syndrome (TGF-beta receptor 1 and 2 gene mutations, sample sent OUS, UUS)
- Menkels disease (Defective in copper metabolism)
- Pseudoxanthoma elasticum
- Stickler syndrome (hereditary arthro-ophthalmopathy).
- Weill-Marchesani syndrome (WMS).
Use of beta-blockers that reduce blood pressure, regular check-ups, limited heavy physical activity and surgery for aneurysms on the main artery and heart valve failure have improved the prognosis significantly, but no curative treatment is available. Regular checks of the blood vessels are important. The average age for surgery is 32 years. Stabilizing orthoses and adapted footwear. The treatment otherwise depends on any complications from the eyes, joints and columna / thorax. No curative (gene therapy) treatment is available.
- If enlargement of the arteries (aneurysms) occur, may surgery to prevent the artery from bursting (aortaruptur) become necessary.
- Karate surgeons / thoracic surgeons have guidelines for when operations should be performed.
- Blood pressure measurements are important to detect any high blood pressure that may increase the risk of aortic aneurysms
- Usual physical activity is recommended. Intensive, hard physical exercise increases the pressure on the blood vessels and should be avoided
- Cortisone and other immunosuppressive treatment have no place in the treatment of hereditary connective tissue diseases, unlike autoimmune connective tissue disease
- Tablets in the form of a beta-blocker can reduce blood vessel complications and are recommended for many
- The treatment is otherwise dependent on any complications from the eyes, joints, spinal column and the like
Follow-up may include MRI angiography represents the most important pulses starting from the head, neck, chest, abdominal area and pelvis. Also included ultrasound Doppler / echocardiography diameter of the main artery at the heart and aortic arch can be measured. If the pulse vein expands, measurements are made at least every six months, otherwise annually for a longer period. Also wood CT examination the entire main artery can be produced. The examination is not done too often due to X-rays.
- Competence Center, Sunnås Hospital
- Salik I, 2022
- Dietz HC, 2001
- Marfan Association in Norway
- Barstow C, 2015
- Grans Compendium in Rheumatology