Marfan Syndrome is a genetic disorder of connective tissue caused by mutations in the FBN1 gene resulting in skeletal, ocular, and cardiovascular abnormalities. It is characterized by disproportionately long limbs, joint hypermobility, eye problems like ectopia lentis, and life-threatening issues like aortic aneurysm. Diagnosis is based on clinical assessment using systemic criteria. Management focuses on surveillance and prevention of complications through beta-blockers, surgery, and potentially losartan which may help slow aortic root growth. Prognosis has improved with current treatments but cardiovascular events remain common.

1. Marfan Syndrome
By: Zakariya Al-nuaimi

2. INTRODUCTION
• Antoine Bernard-Jean
Marfan (June 23, 1858 –
February 11, 1942), a
French pediatrician.
• In 1896, Marfan described a
hereditary disorder of
connective tissue in a 5 yr
old girl with
disproportionately long
limbs that later became to
be known as Marfan
syndrome

3. INTRODUCTION
• Marfan syndrome (MFS) is an
inherited, systemic, connective
tissue
• disorder caused by autosomal
dominant mutations in the
gene encoding the
extracellular matrix (ECM)
protein fbrillin-1.
• It is primarily associated with
skeletal, cardiovascular, and
ocular pathology

4. EPIDEMIOLOGY
• incidence is reported to be 1 in
10,000 live births
• approximately one-fourth of
cases are sporadic
• The disorder shows autosomal
dominant inheritance
• with high penetrance, but
variable expression both
interfamilial and intrafamilial
clinical variation is common.
• There is no racial or gender
preference

5. PATHOGENESIS
• MFS is associated with abnormal production, matrix
deposition and/or stability of fbrillin-1
• fibrillin-1, a glycoprotein component of the
extracellular matrix protein that is the major
constituent of microfbrils
• The extracellular matrix is critical for both the
structural integrity of connective tissue, but also
serves as a reservoir for growth factors
• MFS was traditionally considered to result from a
structural defciency of connective tissues.
• The fbrillin-1 (FBN1) locus resides on the long arm of
chromosome 15 (15q21), the involvement of FBN1
has been demonstrated in >90% of cases

6. PATHOGENESIS
• Elastic fibers are found throughout the body, but are
particularly abundant in the aorta, ligaments and the
ciliary zonules of the eye
• Transforming growth factor beta (TGF-β) plays an
important role in Marfan syndrome
• The simplest model of Marfan syndrome suggests
reduced levels of fibrillin-1 allow TGF-β levels to rise
due to inadequate sequestration
• (TGF-β) family of cytokines influences a diverse
repertoire of cellular processes, including cell
proliferation, migration,differentiation,
• (TGF-β) in MFS is high which mean more growth

7. CLINICAL MANIFESTATIONS
MFS is a
multisystem
disorder with
cardinal
manifestations in
the skeletal
cardiovascular
ocular systems

8. Skeletal System
1. Long and slender fingers (arachnodactyly)
2. the Walker-Murdoch or (wrist sign)
3. the Steinberg or (thumb sign)
4. Anterior chest deformity outward (pectus
carinatum) or inward (pectus excavatum).
5. flatfeet (pes planus)
6. (protrusio acetabuli)
7. Abnormal curvatures of the spine (scoliosis)
8. joint hypermobility
9. Contracture of the fingers (camptodactyly)
and elbows is commonly observed
10. long narrow skull (dolichocephaly)
11. recessed lower mandible (retrognathia) or
small chin (micrognathia),
12. flattening of the midface (malar hypoplasia)
13. Overgrowth of the long bones
(dolichostenomelia)

9. Cardiovascular System
1. Aortic aneurysm, dissection and rupture
principally at the level of the sinuses of
Valsalva (aortic root) the most life-threatening
manifestations of MFS
2. thickening of the atrioventricular valves is
common and often associated with valvular
prolapse
3. In children with early onset and severe MFS
insufficiency of the mitral valve can lead to
congestive heart failure , pulmonary
hypertension and death in infancy
4. Dilated cardiomyopathy
5. Aortic valve dysfunction
6. Dilation of the main pulmonary artery is
common
7. Enlargement of the descending thoracic or
abdominal aorta can also occur, although
relatively rarely.

10. Ocular System
1. Dislocation of the ocular lens (Ectopia
lentis ) occurs in approximately 60-70%
of patients
2. early and severe myopia
3. flat cornea
4. increased axial length of the globe,
5. hypoplastic iris
6. ciliary muscle hypoplasia, causing
decreased miosis.
7. Patients are also predisposed to retinal
detachment and early cataracts or
glaucoma.

11. Other Systems
1. Widening of the Dural sac or root
sleeves (Dural ectasia) is present in
63-92% of MFS patients
2. Another common manifestation is
congenital or acquired inguinal hernia
3. pulmonary disease in MFS .widening
of the distal airspaces predisposes
patients to spontaneous
pneumothorax,which occurs in up to
15% of patients.
4. most common skin finding is stretch
marks—pinkish, scar-like lesions that
later become white (striae
atrophicae)

12. DIAGNOSIS

13. DIAGNOSIS

14. DIFFERENTIAL DIAGNOSIS
 Aortic Aneurysm Syndromes
 Loeys-Dietz syndrome (LDS)… TGFBR1 or the TGFBR2 gene
 familial thoracic aortic aneurysm
 Shprintzen-Goldberg syndrome…SKI gene..FBN1 gene
 Ectopia Lentis Syndromes
 Weill-Marchesani syndrome..FBN1 gene
 Homocystinuria
 Familial ectopia lentis.. FBN1 gene
 SYNDROMES WITH SYSTEMIC MANIFESTATIONS OF MFS
 Congenital contractural arachnodactyly .. fbrillin-2(FBN2)
 MASS (mitral valve prolapse, aortic enlargement, skin and skeletal
findings) syndrome.. FBN1 gene

15. LABORATORY FINDINGS
Most, if not all, people with
classic MFS have an FBN1
mutation, the large size of this
gene and the extreme allelic
heterogeneity in MFS have
frustrated efficient molecular
diagnosis. The yield of
mutation screening varies
based on technique and
clinical presentation

16. MANAGEMENT
• Management focuses on preventing
complications and genetic counseling.
• Yearly evaluations for cardiovascular disease,
scoliosis, or ophthalmologic problems are
imperative.

17. CURRENT THERAPIES
ACTIVITY RESTRICTIONS
Physical therapy can improve cardiovascular
performance, neuromuscular tone, and
psychosocial health
AORTIC SURGERY
aortic surgery should be recommended for
adult patients when their aortic root diameter
approaches 50 mm

18. PREGNANCY
Prophylactic aortic root replacement can
minimize the risk of aortic dissection and death in
women with MFS who wish to become pregnant
ENDOCARDITIS PROPHYLAXIS
the National Marfan Foundation believes that
patients with MFS should continue to receive
prophylaxis for bacterial endocarditis, in part
because it remains unknown

19. Current Pharmacologic Approaches
β-Blockers
β-Blockers have traditionally been considered
the standard of care in MFS
 multiple small observational studies suggest
there is a protective effect on aortic root
growth

20. EMERGING THERAPEUTIC STRATEGIES
Angiotensin II Receptor Type 1 Blockers{losartan}
 There is extensive evidence linking angiotensin II
signaling to TGF-β activation and signaling
 A retrospective study assessing the effect of
angiotensin II receptor type 1 blockers in a small cohort
of pediatric patients with MFS who had severe aortic
root enlargement despite previous alternate medical
therapy, showed that angiotensin II receptor type 1
blockers significantly slowed the rate of aortic root and
sinotubular junction dilation (both of which occur in
MFS)

21. PROGNOSIS
early diagnosis and refined medical and surgical
management has greatly improved the
prognosis for patients with the condition.
In the more classic form of MFS, it is estimated
that more than 90% of individuals will have a
cardiovascular event during their lifetime
In a review of 54 patients diagnosed during
infancy, 89% had serious cardiac pathology;
cardiac disease was progressive despite
standard care (22% died during childhood, 16%
before age 1 yr).

23. REFERENCE
• Nelson…TEXTBOOK of PEDIATRICS….EDITION
20
• Chapter 702.Marfan Syndrome.Alexander
Doyle, Jefferson J. Doyle,and Harry C. Dietz III.
Page 3384 PartXXXII ◆ Bone and
Joint Disorders