
Marfan Syndrome. Illustration: Thumb and little finger meet at Marfan's syndrome. Illustration from Staufenbiel I et al. CC BY 2.0
Marfan's syndrome. ICD-10 Q87.4
Contents
Definition
Marfan Syndrome is a hereditary (genetic) disease (autosomal dominant) caused by defect (misfolding) in the protein fibrillin-1 encoded by the gene FBN1 on chromosome15. Thus, Marfan's syndrome is a congenital, genetic condition that differs from the systemic autoimmune connective tissue diseases. About 25% are spontaneous mutations without family disposition (Big Norwegian Leksikon, A Heiberg 2009). Along with 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.
Occurrence
Prevalence: 1 among 20.000 persons (approx. 500 in Norway). Marfan's disease is thus defined as one rare disease.
Symptoms

Marfan Syndrome. Long, thin fingers at Marfan's syndrome. Illustration: Department of Pedodontics, SRM Dental College, SRM University, Chennai 600078, India. CC BY 3.0
The skeletal system
- Strikingly high body height
- Sideways curved back (Scoliosis)
- Long, arms and legs (dolichostemomeli) with long fingers and toes (arachnodaktyli) in relation to the body length
- Breast bone deformities as bird breasts (pectus carniatum)
- Overstrechable (hypermobility) joints
- Reference: Kaissi AA, 2013
Eyes
- Often severe vision disorders with myopia (myopia) and Astigmatism (astigmatism)
- Lens subluxation (ectoptic lens) detected by the ophthalmologist.
- Glaucoma (glaucoma)
The heart and blood vessels
- Most serious complications that can be life threatening
- Irregular heart rhythm
- Heart valve leak
- Extended diameter of the aorta artery (aortic aneurysm)
- Aortic dissection (Damage and leakage of the bloodvessel wall)
- Special attention in pregnancy is important
Lungs
- Spontaneous pulmonary puncture (pneumothorax) occurs
Diagnosis
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
- Often spontaneous mutation (25%)
- Mutation in the gene FBN1 can be detected at approximately 85% with clinically Marfan's disease (reference: Store Norske Leksikon, Heiberg A, 2009). Sample can be sent to Oslo University Hospital, Ullevål
- More about genetic testing here (Genetikkportalen.no)
Prognosis
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.
Incorrect diagnosis? (Similar diseases / differential diagnoses)
- Hereditary thoracic aortic aneurysm (HTAD)
- Ehlers-Danlos syndrome
- 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
Treatment
No curative 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.
- Such interventions are carried out, among other things, at Rikshospitalet in Oslo
- 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
Regular blood vessel monitoring is important
- MRI angiography produces the major arteries from the head, neck, chest, abdomen and pelvis
- Also included ultrasound Doppler / echocardiography the diameter of the main artery at the heart and the aortic arch can be measured
- If the artery expands, measurements are made at least every six months, otherwise annually for a longer period
- Also by CT examination the entire main artery can be displayed. The investigation is not done too often because of X-rays
Referral to specialist
- Patients living in Oslo can be investigated by Oslo University Hospital HF, Department of Physical Medicine and Rehabilitation, Mailbox 4956 Nydalen, Ullevål hospital, 0424 Oslo
- In case of diagnosed disease (no further medical examinations required), the current address is: TRS competence center for rare diagnoses, Sunnaas Hospital HF, 1450 Nesoddtangen.
Literature
- Competence Center, Sunnås Hospital
- Wikipedia (English)
- Dietz HC, 2001
- Marfan Association in Norway
- Barstow C, 2015
- Grans Compendium in Rheumatology