What is Marfan Syndrome?
Marfan syndrome describes a complex hereditary disorder of the connective tissue, which mainly affects the eyes, cardiovascular system and skeletal muscle system. However, considering that every organ is made up of connective tissue, Marfan syndrome can ideally destroy and interfere heavily with growth and function of each anatomical site.
The syndrome is transmitted as an autosomal dominant trait: we are therefore faced with a serious genetic disease, having an extremely variable phenotypic expression (defects can differ enormously from family to family or from patient to patient).
What triggers Marfan syndrome is the alteration of the FBN1 gene (on chromosome 15), which codes for fibrillin-1, a very important connective glycoprotein that constitutes the structural support for microfibrils.
Microfibrils: consisting of fibrillin, the microfibrils are present in the extracellular matrix, in which they form a web for the deposition of the elastin in the elastic fibers. Although ubiquitous in the body, microfibrils abound mainly in the aorta, ligaments and zonules of ciliary bodies (at the ocular level).
Being an autosomal dominant disease, only children who have inherited an FBN-1 gene altered by both parents are affected by Marfan syndrome. Nevertheless, in one case out of 4 the disease is the result of spontaneous mutations in patients who do not have a family history.
The name of the disease comes from the French pediatrician who first described it in 1896 (A. Marfan), after which it had to wait until 1991 to identify the altered gene involved in the symptomatic manifestation: the discoverer was F. Ramirez.
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We have mentioned that Marfan syndrome is the immediate expression of the mutation of a gene that codes for fibrillin-1. Let us try to deepen the topic to understand which mechanism is established to trigger the syndrome.
FIBRILLINA 1 is a glycoprotein component of elastin, essential for ensuring and maintaining elasticity and tissue strength. In physiological conditions, fibrillin 1 binds to another protein, known as TGF-beta (or transforming growth beta factor). TGF-beta appears to be involved in deleterious processes affecting vascular smooth muscle and the extracellular matrix. Starting from these assumptions, some authors are convinced that the Marfan syndrome is due, in addition to the mutation of the FBN-1 gene, also to an excess of TGF-beta, especially in the aorta, in the heart valves and in the lungs.
Incidence
It is estimated that Marfan syndrome affects 1 subject every 3, 000-5, 000 births and manifests itself indistinctly between males and females, without predilection for a precise breed. Statistics show that 75% of patients have a positive family history; in the remaining 25% the cause lies in sporadic mutations that seem to be associated, in some way, with the advanced age of the father at the time of conception.
Children with extremely severe forms of Marfan syndrome have a life expectancy of less than one year.
Before the evolution of open heart surgical strategies, most patients with Marfan syndrome had an average life expectancy of 32 years; thanks to the constant improvement of medical and pharmacological therapies, currently Marfan syndrome patients live on average up to 60 years.
Signs and symptoms
To learn more: Symptoms Marfan syndrome
Marfan syndrome can run completely asymptomatic. Affected patients have an excessively slender structure, being disproportionately tall and thin. The lower and upper limbs have a much higher length than the trunk (dolicostenomegalia). There is also talk of arachnodactyly to best express the concept of the exaggerated length of the fingers, typical of subjects affected by Marfan syndrome: the hands are therefore compared to the legs of a spider.
As for height, these patients have an average height above the 97th percentile.
Other distinctive features often found in patients with Marfan syndrome include:
- Arms open greater than height
- Loose joints → exaggerated joint mobility
- Deformation of the chest wall
- Crystalline displacement
- Upper part of the body less developed than the lower part
- Spontaneous pneumothorax (11%)
- Scoliosis
- Skin striae at thigh, back, deltoid, pectoral level
Among the most problematic signs associated with Marfan syndrome, we mention heart valve prolapse and mitral valve insufficiency: a similar condition can easily promote dilation of the aortic ring and aortic dissection.
The table shows the signs that can be found in patients with Marfan syndrome. The characters described there are not always present, but a good part of these can be found.
| Affected anatomic site | Possible symptoms |
Skin | Striae in the thoracic, lumbar and sacral area |
Eyes | Impairment of vision, astigmatism, retinal detachment, narrow-angle glaucoma, lens dislocation, myopia |
Bone structure | Arthralgia, kyphoscoliosis, dolicostenomelia (excessive development in limb length compared to the trunk), hypermobility, high palate, deformed chest, flat feet, narrow and thin wrists, abnormal re-entry / sternum protrusion, scoliosis, curved shoulders, spondylolisthesis |
Dita | arachnodactyly |
Lungs | Spontaneous pneumothorax, dyspnea, idiopathic pulmonary obstructive disease |
Facial changes | Ogival palate (malformation of the palate), mandibular retrognathia (defect in the development of the jaw), elongated face |
Heart | Angina pectoris, abdominal aortic aneurysm, cardiac arrhythmia, thoracic aorta dilation / rupture / dissection, aortic insufficiency, mitral valve prolapse |
Language | Language difficulty |
Diagnosis
Considering the more than 200 possible mutations, the use of genetic markers is almost impossible for diagnostic purposes.
The ascertainment of Marfan syndrome is not always so immediate, given that the phenotypic expression of the mutation is not always obvious and simple to identify. The diagnostic delay can seriously compromise the patient's survival: just think, for example, of the failure to recognize a cardiovascular problem.
The diagnostic criteria for Marfan syndrome were drawn up internationally in 1996: the diagnosis consists in the investigation of the family history associated with a combination of major and minor indicators of the syndrome.
Some of the many diagnostic tests used are:
- echocardiogram
- Magnetic angiorisonance and CT (for the investigation of the aorta)
- magnetic resonance angiography (MRA) with contrast fluid (to make internal structures of the aorta evident)
- examination with slit lamps (to analyze the possible dislocation of the lens)
- measurement of ocular pressure (to highlight the possible presence of glaucoma)
- genetic tests (recommended before conceiving a child to ascertain the syndrome or not)
therapies
Being a genetic disease, there is no drug or treatment that can reverse the disease.
The use of drugs is however essential to mitigate the symptoms and avoid any complications, in particular cardiac ones. For this purpose, drugs to reduce blood pressure, such as sartans (especially), ACE inhibitors and beta-blockers, are particularly suitable.
In the context of Marfan syndrome, patients also suffering from scoliosis can follow specific care, as well as for those affected by glaucoma.
Surgery is conceivable to correct the anomalous aortic dilation, an element that often unites the majority of patients with Marfan syndrome.
Continue: Marfan Syndrome - Drugs and Care »
