Page 250 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 9-9 Integumentary System

MARFAN SYNDROME Tall, thin person with
skeletal disproportion.
Marfan syndrome is an autosomal dominantly inherited Upper body segment
(top of head to pubis)
disorder of connective tissue that is caused by a genetic shorter than lower body
defect in the FBN1 gene located on chromosome 15. segment (pubis to soles
The disorder leads to a defect in the fibrillin-1 protein, Upper body segment of feet). Fingertips reach
which is a component of the extracellular matrix of con- almost to knees (arm
nective tissue. The defect leads to many clinical findings span-to-height ratio
in the cardiovascular, ocular, skeletal, integumentary, greater than 1.05).
and respiratory systems. The diagnosis is made based on Long, thin fingers Ectopia lentis (upward and temporal
multiple criteria that include major and minor features (arachnodactyly). displacement of eye lens). Retinal
of the syndrome. Cardiovascular disease is a major cause Scoliosis, chest detachment, myopia, and other
of morbidity and mortality in this syndrome. deformity, inguinal ocular complications may occur.
Clinical Findings: Marfan syndrome has an esti- hernia, flatfoot
mated incidence of approximately 1 per 7500 people. It
affects all populations and has no gender differential.
Many of the manifestations of the syndrome are present
at the time of birth. As the child grows, the findings
become more evident and the severity may worsen. The
diagnosis of Marfan syndrome does not imply any spe-
cific prognosis, because the syndrome has a range of
clinical manifestations. On one end of the spectrum is
the patient with life-threatening disease, and at the
other end is the patient who has only the musculoskel- Lower body segment
etal clinical features of the syndrome.
Many skeletal anomalies can be seen, including
arachnodactyly, pectus excavatum, scoliosis, pes planus,
high palate, and an increased lower body to upper body
ratio. The most striking features are tall stature, thin Walker-Murdoch wrist
body habitus, long arms, and disproportionate lower- sign. Because of long
to-upper body ratio. fingers and thin forearm,
Cutaneous findings of Marfan syndrome may be thumb and little finger
subtle. The presence of striae distensae is almost uni- overlap when patient
versal. Adipose tissue is decreased, and patients often grasps wrist.
appear extremely thin. Elastosis perforans serpiginosa
is seen with a high incidence in Marfan syndrome and
is caused by the extrusion of abnormal elastic tissue
through the epidermis. Ocular involvement often leads
to an upward displacement of the lens (ectopia lentis).
Myopia is often seen, as well as a decreased ability to
constrict the pupil.
The respiratory and cardiovascular systems are com-
monly affected. Pulmonary blebs can be seen in an
apical location. The blebs may spontaneously rupture,
causing a pneumothorax. Severity of involvement of the
cardiovascular system is the best prognostic indicator in
Marfan syndrome. Prolapse of the mitral valve, aortic
root dilation, and early-onset calcification of the mitral
valve anulus are a few of the cardiovascular findings.
The leading cause of mortality is rupture of an aortic
aneurysm or aortic dissection.
Pathogenesis: Fibrillin-1 is a glycoprotein found in a
wide range of connective tissues. Fibrillin-1 is required
for proper elasticity and strength properties of the
extracellular matrix. Many hundreds of mutations have Dilatation of aortic ring and aneurysm of
been reported in the gene that encodes fibrillin-1. ascending aorta due to cystic medial necrosis
There is a wide phenotypic variability in Marfan syn- cause aortic insufficiency. Mitral valve prolapse Radiograph shows acetabular
drome, due in some part to the different mutations of causes regurgitation. Heart failure is common. protrusion (unilateral or bilateral).
the gene but also to other, as yet undescribed factors.
This leads to a large variation in phenotype among
individuals with the same genotypic mutation. dissection of arterial walls, with the aorta being the Calcium channel blockers and angiotensin-converting
Defects in the fibrillin-1 protein lead to a decreased most commonly affected vessel. enzyme (ACE) inhibitors are second-line agents.
ability to bind to calcium. This ultimately manifests as Treatment: All patients with Marfan syndrome should Patients with Marfan syndrome who are closely fol-
abnormalities of the microfibrils throughout the con- be monitored directly by a cardiologist and a cardiotho- lowed and treated promptly may live a normal life span.
nective tissue. These abnormal microfibrils are more racic surgeon as needed. Routine echocardiograms They must be educated to avoid strenuous physical
susceptible to degradation by matrix metalloprotein- and evaluations for aortic aneurysms are required. activity and contact sports. Surgery to repair aortic dila-
ases, and when they occur within the connective tissue β-Blockade has been shown to be helpful to decrease tion and aneurysm is required once the caliber of the
lining of the vascular walls, the lining’s elastic and mean arterial pressure. This reduces the pressure on the aorta reaches 5.0 cm or if the rate of enlargement is
strength properties are compromised. This may lead to weakened vessel walls and subsequently decreases the greater than 0.5 cm/year. Ocular disease should be
dilation, increased stiffness, aneurysm, and eventual likelihood of arterial dilation, dissection, and aneurysms. evaluated and treated promptly by an ophthalmologist.

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