Introduction
Marfan syndrome is named after the French paediatrician Antoine Marfan, who first described the condition in 1896 after observing the outstanding features in a five-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Centre in New York City in 1991 (Katarina et al, 1990). Marfan syndrome is an inherited disorder that harms the body’s connective tissue such as blood vessels and capillaries. This tissue holds all the body’s cells, organs and tissue collectively. It as well plays an important role in allowance of the development of the human body and also its advancement properly (NCBI, 2012).
Connective tissue is fabricated up of proteins. A protein that plays a role in Marfan affection is suspected as fibrillin-1 FBN-1. Marfan’s syndrome is acquired by a birth defect by means of genetic mutation in the gene that tells the body how to secrete out fibrillin-1. This post effects of genetic mutation in the enhanced level in a protein so-called transforming growth factor beta, or TGF-β (NCBI, 2012). The up regulation in TGF-β causes problems in connective tissues throughout the body, which in about-face creates the appearance and medical problems associated with Marfan syndrome and some accompanying disorders too. Since connective tissues are universal and throughout the body, Marfan syndrome can affect complete genetically mutated locations of the body, as well. Clinical manifestation of the disorder are a lot of normally begin in the heart, claret vessels, bones, joints, and eyes (NCBI, 2012)
Symptoms
The patients with Marfan’s syndrome appear so tall, thin shoulders and limbs as well as characterised by spider-like fingers. This condition is named as arachnodactyly. (Kainulainen et al, 1994)
- Patient’s chest may bulge outward or involute inward inside the chest, namely funnel chest known as pectus excavatum or pigeon breast called as pectus carinatum (Kainulainen et al, 1994)
- Flat feet
- Highly arched palate and crowded teeth
- Hypotonia
- Joints that are too flexible except for the but the elbows may be less flexible (Kainulainen et al, 1994)
- Learning disability
- Movement of the lens of the eye from its normal position or eye lens dislocation
- Nearsightedness (Kainulainen et al, 1994)
- Small lower jaw also called as Micrognathia
- Spine that bends to a single side is called as scoliosis (Kainulainen et al, 1994)
- Thin, narrow face
Diagnosis
Physical examination
Doctor’s physical examination may identify the aneurysm which means the abnormal blood vessel widening, collapsed lung and also heart valve problems (Dietz et al, 2005). Also, the eye examination may signify the ocular lens defects which are associated with eye, retinal detachment and other visionary problems. In the non-invasive diagnosis, ECG and Fibrillin—1 mutation testing are done to investigate the heart valve problems and also mutation in the suspected FBN-1. ((Kainulainen et al, 1994)
Pathogenesis
The FBN-1 gene mutation found in the location 15 is the chief cause for Marfan’s syndrome. This FBN-1 gene encodes for the glycofibrillin-1 which is a protein present in the extracellular space (EC matrix) of the cells. Fibrillin-1 protein has wide ranging functions such as synthesis and maintenance of components of elastic fibers for connective tissues in the joint (Kainulainen et al, 1994). The extracellular matrix is responsible for the integration of proper structure. Besides, maintaining the structure, it has a key role of acting as a reservoir for the growth factors such as IGF, TGF, EGF, FGF etc. Fibrillin-1 maintains the elastic fibers in heart valves, aorta, ligaments and also the ciliary zonules present in the eye. (Kainulainen et al, 1994)
The identified pathogenesis is fibrillin-1 from the defective gene binds with the TGF-β and prevents the TGF-β from its activity by inhibiting the binding of TGF-β from its cognate receptors. This causes the increased levels of TGF-β in the circulation causes the release of proteases which degrades the elastic fibers in the heart valves and other connective tissues. (Cameroon et al, 2005)
Treatment
Beta Blocker therapy is used to treat the aortic dilation in the patients with Marfan syndrome. Also verapmil is given as additional to treat the aortic dilations. (Martin et al, 2008)
Surgical options are also available for the Marfan syndrome patients. There are two types of surgery Type A and B
Type A- A fused valve graft.
In this surgery, a phase within the arteria and additionally within the semilunar valve is disconnected. The arteria is substituted with a synthetic tube referred to as a graft. A synthetic valve replaces the first valve. (Martin et al, 2008)
Type B- arterial blood vessel valve-sparing surgery.
In conditions were the semilunar valve is functioning well, surgeons may suggest the advocate valve-sparing surgery. In the above surgery, the surgeon substitutes the bulged part in the atria with a graft. Your semilunar valve is left in situ (Diana et al, 2005)
Severe spinal curvature is also treated with a brace or surgery to alleviate the dislocation. Marfan syndrome will cause several eye issues, like a separated lens, ametropia, early eye disease (high pressure within the fluid within the eyes), associate degree cataracts (eye's lens’ clouding). (Martin et al, 2008)
Glasses or contact lenses will facilitate with a number of these issues. Generally a surgery is required. Marfan syndrome will cause meninx distension. During this condition, a substance referred to as the dura mater (which wraps the in and around of brain and spinal cord) bulges and develops so weak. This could be a reason for the spinal cord bone’s to carry away causing a Meninx distension typically is treated with painkiller tablets and injections. (Martin et al, 2008)
Marfan syndrome could cause abnormal, or folded respiratory organ. During this condition, air builds up within the area between the lungs and also the plural cavity wall. If this is a minor case, the air must be expelled automatically. However, you will have to be instructed to have a tube punctured through the skin and wall of the pleural cavity to get rid of the air, generally surgery is required. (Martin et al, 2008)
In this surgical treatment, a segment in the aorta and also in the aortic valve is disconnected. The aorta is substituted with an artificial tube namely a graft which is similar to aortic valve. An artificial valve substitutes the original valve. (Martin et al, 2008)
Marfan syndrome may cause pneumothorax, or lung collapse. In this pathogenesis may be observed as the accumulation of air (oxygen or carbon-di-oxide) in the pleural cavity which is found between the lungs and the pleural cavity wall of the patients. If the case is of the minor diseased level, it may get cured automatically. (Martin et al, 2008)
Physiotherapy is always needed for the normal movement of the bones and joints as well.
Gene Inheritance pattern for Marfan’s Syndrome
(Source: Stanford Childrens health, 2014)
Marfan’s syndrome is a type of autosomal dominant inheritance. The human chromosomes are 23 in total. Out of 23, 22 are autosomes. The defective gene can be mapped and identified in all chromosomes except from the 23rd sex chromosome. When a normal parent and abnormal gene containing parent give births to children, the abnormal gene located in chr 15 dominates and so, the disease gets transmitted to the son or daughter. (NCBI, 2012)
Conclusion
Marfan’s syndrome occurs 1 in 5000 children. This is a kind of autosomal dominant inheritance disorder. The gene responsible for the Marfan syndrome is called fibrillin-1 (FBN-1) (Clinvar, 2014). This gene is localized to chromosome 15 on the long arm (q) at 15q21.1.is the position in the chromosome. It was also found that a patient with Marfan’s syndrome has 50% risk to cause the same genetic disorder for his descendants. So, such diseases must be identified earlier and treated to prevent fatality.
References
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