1. Lee AnnWayland
Marfan Syndrome Identified
In 1875, Dr. E. Williams became the first recorded individual to describe an enigmatic
condition that he had identified in a father and two of the man’s biological children. Williams
reported to the American Ophthalmological Society that the three individuals had displaced
lenses along with loosely jointed arms and legs. Twenty-one years later, Antoine Bernard-Jean
Marfan of Paris described a similar condition that he had identified in a five-year-old female who
exhibited “exceptionally long limbs, lanky build, and poor muscular strength” (Gonzales 2009:
663). In 1902, the syndrome officially became known as Marfan Syndrome (Gonzales 2009).
Mode of Inheritance
Marfan syndrome is inherited through an autosomal dominant pattern of inheritance and
is caused by a mutation that occurs on the gene that codes for the glycoprotein fibrillin. The
proband, or the person in which the mutation occurs, has a 50% chance of passing the disease on
to each of his or her offspring. Because the mutation in the gene that causes the disease is
dominant, an individual only needs to inherit one copy of the affected gene from either parent for
the disease to develop. Yet, Gonzales (2009), Iams (2010), and Bentley (2013) report that more
than 25% of the individuals who are diagnosed with the disease are affected as a result of a new
mutation, not inheritance (Milner 2005).
Molecular Basis
According to Gonzales (2009), 90% of the cases of Marfan syndrome are caused by a
mutation in the fibrillin-1 gene. Gonzales (2009) also reports that some of the mutations occur on
the fibrillin-2 gene which is located on chromosome 5. Iams (2010) suggests that most of the
mutations occur on the fibrillin-1 gene which is located on chromosome 15, but she does not
offer any evidence suggesting on which gene other mutations occur. However, Milner (2005)
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and Bentley (2013) concur that the mutation occurs on the fibrillin-1 gene (i.e. FBN-1gene) and
that all individuals who are affected have a mutation on the FBN-1 gene. The 2010 revised
Ghent criteria provides that the FBN-1 mutation must accompany one of two conditions (see
page 4) in order to diagnose an individual who has no family history of Marfan syndrome
(National Marfan Foundation 2011). Because all references agree that mutations do occur on the
FBN-1 gene and that these mutations can cause Marfan syndrome, I will use the evidence that
supports this indication for this paper.
Physiological Basis
The fibrillin protein that is damaged by the mutation is associated with the molecular
structure of the connective tissue that is necessary for the numerous normal bodily functions or
the physiological systems in humans. Some examples of connective tissue include ligaments,
tendons, cartilage, fat, collagen, muscle, and elastin. Some of these connective tissues, such as
cartilage and muscle, act as supports and adhesive substances for skeletal parts and organs (e.g.
bladder) in the body. Other connective tissues, such as elastin, enable the extensive network of
veins and arteries to expand and contract which is essential for the healthy flow of blood
throughout the body (Milner 2005; Gonzales 2009; Bentley 2013).
Effects
Marfan syndrome is pleiotropic which indicates that the affected gene can cause many
different effects. Therefore, each individual that is affected by the syndrome will express some
of symptoms associated with the disease, yet there is no systematic pattern that supports which
symptoms will be expressed by an individual with the disease. Individuals with Marfan
syndrome may experience an ocular condition, skeletal deformities, cardiovascular problems, or
a combination of these effects (Milner 2005; Gonzales 2009; Bentley 2013).
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This syndrome is considered to have variable expressivity which means that some
individuals who are affected with the disease will exhibit severe symptoms associated with the
disease while others will have very mild symptoms (Milner 2005; Bentley 2013; Genetics Home
Reference 2013). An individual who is diagnosed with a severe case of Marfan syndrome will
have some symptoms related to each of the three critical classifications (i.e. ocular, skeletal, and
cardiovascular) of the disease (Milner 2005; Gonzales 2009; Bentley 2013). According to
Gonzales (2009), severe MFS is characterized by a triad of symptoms: displaced lens (i.e. ocular
condition); long, thin extremities, loose joints and extremely long fingers and toes (i.e. skeletal
condition); and an aneurysm of the aorta (i.e. cardiovascular condition).
The 2010 revised Ghent criteria includes a diagnostic criterion for an individual who has
a family history of Marfan syndrome and a diagnostic criterion for an individual with no family
history. In addition, this revision classifies the aortic conditions using a statistical measurement,
referred to as a Z-score, that places a value on the problem of either [≥ 2] or [≥ 3]. Some of the
other features of the syndrome are listed as systemic features and are assigned a numerical value
ranging from [1] to [3]. The 2010 revised diagnostic criteria is the reference list used for all
features listed in this paper ( National Marfan Foundation 2011; Bentley 2013).
Marfan syndrome has the most profound effect on the aorta which is the major artery
carrying oxygenated blood away from the heart (Bentley 2013). The aorta’s diameter is the
greatest at the aortic valve, and the diameter decreases as the distance from the aortic valve
increases. An aortic root that has a diameter of roughly 3cm is considered normal for an adult,
but 96% of individuals with Marfan syndrome have an aortic root than has expanded beyond the
normal range (Bentley 2013).
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The cardiovascular complications associated with Marfan syndrome are responsible
for the greatest health risks and deaths. If the elastin in the aorta is damaged by the mutation,
dilatation (i.e. expansion) of the aortic root can occur. This expansion can lead to the wall of the
aorta weakening and becoming enlarged which then becomes an aneurysm. The aneurysm can
separate into pieces and is responsible for 20% of the deaths that occur in individuals that have
Marfan syndrome. Other cardiovascular conditions include the following:
Mitral valve prolapse in which the heart valves on the left hand side of the heart may not
form a tight seal allowing blood flow back (regurgitation) into the heart
Aortic dissection in which the inner layer of the aorta develops a tear (Mayo Clinic1998)
Aortic valve regurgitation which can contribute to the aortic root dilatation
Although an individual who suffers from mitral valve prolapse is considered to have a systemic
value of [1], 25 % of these individuals who also experience regurgitation with mitral valve
prolapse may require surgery to prevent the blood flow back into the heart (Milner 2005;
Gonzales 2009; Bentley 2013).
According to Bentley (2013), an individual who does not have a family history of Marfan
syndrome, can be diagnosed using one of four criteria. The four criteria are listed below:
Ao (Z≥ 2) AND ectopia lentis (i.e. displaced lens)
Ao (Z≥ 2) AND FBN1 mutation
Ao (Z≥ 2) AND systemic features (≥ 7 points)
Ectopia lentis AND FBN1 mutation associated with known aortic involvement
The abbreviation, Ao, represents the aortic diameter or aortic root dissection that has a Z-score
greater than or equal to [2] ( National Marfan Foundation 2011).
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For an individual who has a family history of Marfan syndrome, there are three criteria,
each of which can be used to make the diagnosis. The three criteria are listed below:
Ectopia lentis (i.e. displaced lens) AND family history of Marfan syndrome
Systemic features (≥ 7 points) AND family history of Marfan syndrome
Ao family history of Marfan syndrome (z ≥ 2 above 20 years, ≥ 3 below 20 years)
Because the diameter of the aorta increases with age, the Z-score for the aortic condition has
been adjusted to compensate for the age increase in the last item listed above (National Marfan
Foundation 2011; Bentley 2013).
Some of the systemic features identified by 2010 revised diagnostic criteria are listed
below, and the value of the feature is shown bolded in brackets at the end of each item:
A breast bone that sinks into the chest (i.e. moderate pectus excavatum Mayo Clinic
1998) [1]
Facial and head characteristics such as a long narrow head (i.e. dolichocephaly); a
receding jaw (i.e. retrognathia); the space between the eyelids slants downward ( i.e.
downslanting palebral fissures); an eyeball which sinks into the orbital cavity (i.e.
enophthalmos); small cheekbones (i.e. malar hypoplasia) three of five facial features
[1]
Wrist and thumb sign (i.e. The thumb can be pushed laterally to touch the wrist.) [3]
Pectus carinatum (i.e. a protrusion of the chest that is birdlike: Medline Plus) [2]
Scoliosis ( i.e. an s-shaped curvature of the spine) [1]
There are actually sixteen categories included in the systemic features list from the 2010 revision
with a maximum total of [20] points. However, an individual that scores at least a [7] is
considered to have a positive systemic score, and the score is used in conjunction with other
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criteria for the diagnosis of the Marfan syndrome as shown in the criteria lists above (National
Marfan Foundation 2011; Bentley 2013).
Environmental Conditions
While there are treatments for the disease such as beta blockers, physical therapy, and
surgical repairs, an affected individual whose financial environment renders the person to be at
an economic disadvantage may not be able to gain access to these treatments. Therefore, the
affected individual may suffer from painful or debilitating conditions such as poor eye sight
caused by myopia (i.e. nearsightedness) or joint pain associated with the damage to the cartilage.
Furthermore, an individual’s life span can be shortened to about 37 years without access to
medical treatment (Milner 2005; Gonzales 2009; Iams 2010; Bentley 2013).
According to the National Marfan Foundation (2011), many of the individuals who have
the syndrome have skeletal features that include long arms, legs, and fingers. An affected
individual who is musically inclined and has long fingers, may have a favorable condition for
playing the piano or guitar. Additionally, an affected individual with long arms may have an
advantageous condition in an environment that requires someone to reach objects that are located
in a long, narrow, confined space. A plumber, for example, who needs to repair plumbing
fixtures that exist between the exterior and interior walls of a building might benefit from having
long arms.
Population Based Afflictions
Milner (2005) and Gonzales (2009) report that there are no populations, based on
ethnicity, social stature, or geographical boundaries, that are affected by the mutation more
frequently than another. Interestingly, Milner (2005) does acknowledge that females experience
mitral valve prolapse more often than males.
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Genetic Counseling
Milner (2005), reports that if at least one partner of a couple who are planning to have
children is suspected of having the mutation, genetic testing will be useful in confirming or
dismissing the diagnosis. If the suspected individual is found to have Marfan syndrome, the
couple might decide not to conceive (Milner 2005; Iams 2010). According to Iams (2010),
genetic testing is also useful in eliminating the possibility of an affected individual’s family
member having the mutated gene.
Genetic testing is needed to identify a mutation in the FBN-1 gene. This mutation is
listed as one criterion in association with an aortic root dissection or in association with ectopia
lentis and aortic root dissection that is necessary for the diagnosis of an individual who does not
have any family history of Marfan syndrome. These conditions are included in the criteria list
above (National Marfan Foundation 2011; Bentley 2013).
Ethical and Social Issues
Ethical issues might arise when trying to determine if an individual has the disease who
exhibits no physical characteristics, but has been positively identified as having the mutation by
genetic testing. Other ethical questions to consider include the following: (1) Will the treatment
plan be influenced by genetic testing? (2) Is clinical diagnosis less reliable than genetic testing?
(Milner 2005).
Social issues that might arise involve discrimination by insurance companies (prior to
Obama Care), and potential employers. Other social issues to consider include the following: (1)
an affected individual who does or does not exhibit the physical characteristics being exposed to
ridicule; (2) anxiety or negative interaction between psychological and social factors
(psychosocial) due to being tested genetically for the syndrome (Milner 2005).
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The psychological damage associated with the skeletal and visual abnormalities are most
likely due to negative social issues that could arise from within the individual’s peer group or
among the individual’s ethnic group. For example, an individual who expresses skeletal
deformities may be mistaken as an individual with low intelligence or be considered to have
been cursed by a deity or evil persona and, therefore, be subjected to mockery by members of
either group.
In summation, Marfan syndrome is caused by a mutation that occurs on the FBN-1 gene.
The mutation causes pleiotropic effects that have variable expressivity. While treatment for some
of the effects is available, socioeconomic status may prevent an affected individual from gaining
access to the treatment. Ethical issues, social issues, and psychological issues are associated with
the syndrome, but there is an organization, the National Marfan Foundation, that is available to
help diseased individuals and their family members cope with physiological problems and
psychosocial issues associated with Marfan syndrome. Genetic testing and research have aided in
the diagnosis of the disease. Perhaps, genetic engineering will one day render the syndrome
curable.
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Bibliography
Bentley, Peter
2013[2007] Marfan Syndrome: biological basis and genetics. In British Journal of Cardiac
Nursing 8(6): 284-288.
Genetics Home Reference
2013 U.S. National Library of Medicine:
http://ghr.nlm.nih.gov/handbook/inheritance/penetranceexpressivity, accessed March 24, 2014.
Gonzales, Elizabeth A.
2009 Marfan syndrome. Journal of the American Academy on Nurse Practitioners 21:663-670.
Iams, Helen D.
2010 Diagnosis and Management of Marfan Syndrome. Current Sports Medicine Reports 9:
93-98.
Mayo Clinic
1998 Mayo Foundation for Medical Education and Research: http://www.mayoclinic.org/,
accessed March 24, 2014.
Medline Plus
ND U.S. National Library of Medicine:
http://www.nlm.nih.gov/medlineplus/ency/article/003321.htm, accessed April 2, 2014.
Milner, Crystal.
2005 Genetics, Screening, and Management of Marfan Syndrome. Clinical Excellence for Nurse
Practitioners 9(4):201- 211.
National Marfan Foundation
2011 Slideshare: http://www.slideshare.net/NationalMarfanFoundation/2010-revised-diagnostic-
criteria-nvn, accessed April 5, 2014.
