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Marfan Syndrome A Clinical Update JAAOS
Marfan Syndrome A Clinical Update JAAOS
Abstract
Adam D. Bitterman, DO Marfan syndrome is a connective tissue disorder that can affect many
Paul D. Sponseller, MD, MBA organ systems. Affected patients present with orthopaedic
manifestations of the syndrome during all phases of life. Pain caused
by musculoskeletal abnormalities often requires definitive
orthopaedic treatment. Orthopaedic surgeons must understand the
phenotypes of Marfan syndrome so they can recognize when
screening is warranted and can appropriately address the skeletal
manifestations. Through medical advancements, patients with Marfan
syndrome are living longer and more active lives. Knowledge of the
latest diagnostic criteria for the disorder, as well as of advances in
understanding the skeletal phenotype, clinical trials of medication
therapy, and lifestyle considerations is important for orthopaedic
surgeons who treat these patients because these clinicians often are
the first to suspect Marfan syndrome and recommend screening.
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Marfan Syndrome: A Clinical Update
Table 1
Revised Ghent Criteria for Diagnosing Marfan Syndrome and Related Conditions
Criteria Diagnosis
AO = aortic diameter at the sinuses of Valsalva with indicated Z-score or aortic root dissection; FBN1 = fibrillin-1 gene; MASS = mitral valve prolapse,
aorta root diameter at the upper limit of normal, striae, and skeletal features similar to Marfan syndrome
a
Without discriminating features of Shprintzen-Goldberg syndrome, Loeys-Dietz syndrome, or vascular form of Ehlers-Danlos syndrome and after
collagen biochemistry and TGFBR1 and 2 and COL3A1 gene testing, if indicated
b
As described in Table 2
c
FBN1 gene mutation that has been identified in a patient with aortic aneurysm
d
FBN1 gene mutation that has not been associated with aortic root aneurysm/dissection
Adapted with permission from Loeys B, Dietz H, Braverman A, et al: The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010;47
(7):476-485.
which require the attention of better identify MFS and related have been removed from the diag-
orthopaedic surgeons. disorders. nostic evaluation. Counseling and
In the revised nosology, several follow-up recommendations for
major changes were made to the those diagnosed with MFS are also
Diagnosis diagnostic criteria for MFS.7 More provided in the revised nosology.
diagnostic weight is given to the The revised classification includes a
The diagnosis for MFS has evolved presence of aortic root enlargement systemic scoring system that empha-
recently, because various clinical and ectopia lentis, the cardinal fea- sizes various clinical features of the
expressions of the disease have tures of MFS (Table 1). Aortic root disease (Table 2). MFS can be diag-
been identified.7 The main clinical measurements have been standard- nosed or excluded using this scoring
attributes of MFS are long bone ized through the use of the Z-score, system in conjunction with the
overgrowth, dislocated lenses of the which accounts for body surface presence or absence of a family his-
eye, and aortic root aneurysm. In area, as well as the aortic root tory of the disorder. The scoring
1991, Dietz et al8 reported that a measurement (ie, aortic root diame- system also accounts for the fact that
mutation of the FBN1 gene resulted ter measurement at the sinus of phenotypic features evolve over time
in MFS, and in 1996, the Ghent Valsalva), seen on echocardiogra- and may not all be present at birth or
nosology criteria were established.9 phy. Genetic testing is emphasized, in young children, enabling pro-
These diagnostic criteria stress the particularly testing for a mutation of viders to identify patients who war-
importance of a positive genetic FBN1, which has a detection rate of rant follow-up.7
finding and help differentiate MFS 97%.10,11 Clinical testing to identify Radiography, family history, and
from other disorders with similar possible alternative diagnoses that genetic testing are used in the diag-
symptoms. More than a decade later, overlap with MFS is recommended, nosis of MFS. It is important for
an expert panel reconvened in Brussels, and certain MFS clinical findings orthopaedic surgeons to recognize
Belgium, to modify the nosology to have been deemed less important or the signs of MFS; however, a
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Adam D. Bitterman, DO, and Paul D. Sponseller, MD, MBA
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Marfan Syndrome: A Clinical Update
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Adam D. Bitterman, DO, and Paul D. Sponseller, MD, MBA
Figure 3 Figure 4
Figure 5
triradiate cartilage in extreme pro- Thakkar et al31 showed that patients AP radiograph demonstrating
trusion (ie, a center-edge angle .45°) who needed THA because of pain protrusio acetabuli, which occurs
is a surgical approach that was had more severe protrusio acetabuli when the center-edge angle of
Wiberg is .40° or the acetabular wall
advocated by Steel.29 In adults with than did the MFS population as a
protrudes $3 mm medial to the
this condition, total hip arthroplasty whole. The authors also noted that, ilioischial (Kohler) line (arrow).
(THA) with appropriate bone graft- in patients with MFS, complications
ing of the medial wall has provided after THA (eg, dislocations, revision,
symptomatic relief.30 infection, implant loosening) were likely are caused by impingement on
Not all patients with MFS and not correlated with the presence of the deeper acetabulum or ligamen-
protrusio acetabuli require THA, but protrusio acetabuli. Dislocations tous laxity, and implant loosening
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Marfan Syndrome: A Clinical Update
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Adam D. Bitterman, DO, and Paul D. Sponseller, MD, MBA
cardiovascular abnormalities are syndrome. J Med Genet 2010;47(7): Marfan syndrome. Spine (Phila Pa 1976)
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