Marfan's syndrome. ICD-10 Q87.4

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

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):

1. Reduced proportion of upper body / lower body ratio (0,85 vs 0,93 in normal)
2. Arachnodactyli (fingers, toes), positive thumb-wrist test)
3. Scoliosis more than 20 degrees or spondylolistesis
4. Medial malleol misalignment giving pes planus (plate foot)
5. Reduced extension of elbows (
6. Pectum carniatum (bird breast) (Differential Diagnosis: Morquio syndrome, Noonan syndrome, Trisomi 18, Trisomi 21, Homocystinuria, Osteogenesis imperfecta, Multiple lentigine syndrome, and Sly syndrome)
7. Pectus excavatum (funnel chest) that requires surgery
8. 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 (in Danish) (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.
• 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 produced. The examination is not done too often due to X-rays.

Literature

• Competence Center, Sunnås Hospital
• Wikipedia (English)
• Dietz HC, 2001
• Marfan Association in Norway
• Barstow C, 2015
• Grans Compendium in Rheumatology

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