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o
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a
l
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urn
a
l
o
f
P
u
b
lic Hea
l
th Science (IJ
P
HS)
Vol
.
4,
N
o
.
4
,
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ecem
b
er 20
1
5
, pp
. 26
9~
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4
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/
IJPHS
A Cas
e
Report
of M
a
rf
an Syndrome wit
h
Literat
u
re Revi
ew
Hemanth Kumar
Kalla, Sw
arna Kum
a
ri,
C
H
Ra
ma
Rao
,
M
K
R
Pa
rt
ha
sarat
h
y
,
S Sur
ya Pr
ak
ash
Red
d
y,
M Re
vathi
Department o
f
I
n
ternal Medicin
e
,
Santh
i
ram Med
i
cal College, N
a
nd
y
a
l, PIN 5185
01, Andhrapr
a
desh, India
Article Info
A
B
STRAC
T
Article histo
r
y:
Received Aug 15, 2015
Rev
i
sed
Sep
20
, 20
15
Accepted Oct 25, 2015
Marfan s
y
ndrom
e (MFS) is a
co
nnect
ive
tissue d
i
sorder th
at
affe
cts m
u
ltipl
e
organ s
y
stem
s. Cardiovascu
l
ar
, oc
ul
ar, and skelet
al
abnor
m
a
lities are
cardin
a
l featur
es of the s
y
ndrom
e. Its inciden
ce is among the highest of an
y
heritable disord
er.Most patients
w
ho have Ma
rfan s
y
ndrome are usually
diagnosed in
cidentally
wh
en they pres
ent for a ro
utine ph
y
s
ical
examinatio
n
for various reasons. The purpose of this
paper is to provide a review of the
liter
a
tur
e
,
as w
e
ll
as des
c
ribe
a 22-
ye
ar-o
ld
m
a
le wi
th M
FS and right
h
y
drour
eteron
ep
hrosis diagnosed
incid
e
ntally
wh
en he
attended
o
u
r hospital
for complaints
of fever and right lo
in pain
.
This
cas
e repor
t em
phas
i
zes
importance of
“Revised Ghent criter
ia” for the diagnosis of
MFS and
highlights v
a
riou
s clin
ical signs o
f
MFS
.
Keyword:
Mar
f
a
n
syndr
ome
R
e
vi
sed G
h
ent
cri
t
e
ri
a
H
y
d
r
ou
r
e
ter
onep
h
ro
sis
Clin
ical sig
n
s
Copyright ©
201
5 Institut
e
o
f
Ad
vanced
Engin
eer
ing and S
c
i
e
nce.
All rights re
se
rve
d
.
Co
rresp
ond
i
ng
Autho
r
:
Hem
a
nt
h K
u
m
a
r
Kal
l
a
,
Po
stgr
ad
u
a
te
(MD
In
tern
al M
e
d
i
cin
e
),
Dept
o
f
I
n
t
e
r
n
a
l
M
e
di
ci
ne,
Sa
nt
hi
ram
M
e
di
cal
col
l
e
ge,
N
a
nd
yal PI
N 51
850
1,
A
ndh
r
a
p
r
ad
esh
,
In
d
i
a.
Em
a
il: k
a
llah
e
man
t
h
@
g
m
ai
l.co
m
1.
INTRODUCTION
M
a
rfa
n sy
n
d
r
o
m
e
, a rare aut
o
som
a
l dom
inant diso
r
d
er
w
a
s first re
po
rte
d
way
back i
n
18
9
6
by
a
Fre
n
ch
pe
diatricianAntonin Marfa
n. T
h
e
pre
v
alence
is about
1:5000 [1]. MFS
was c
h
aracteri
zed
by
Muscul
os
keletal features, include st
ature
greater tha
n
95pe
rce
n
tile and
lim
b
s disproportionately long for
tr
un
k size (
a
rach
nod
actyly)
, sco
lio
sis,
pec
t
us e
x
cavat
um or ca
rinatum
,
higha
r
che
d
palate, flat feet
and
m
a
rked l
a
xi
t
y
of
j
o
i
n
t
s
.
Oc
ul
ar feat
ures i
n
c
l
ude
no
n
-p
r
o
gressi
ve
up
wa
rd s
u
bl
u
x
at
i
o
n
of l
e
ns a
nd
m
y
opi
a.
C
a
rdi
o
vasc
ul
ar
m
a
ni
fest
at
i
o
n
s
i
n
cl
ude m
i
t
r
al
val
v
e pr
ol
a
p
s
e
and
di
l
a
t
a
t
i
on o
f
ascen
di
n
g
aort
a w
h
i
c
h l
e
ad t
o
mitr
al o
r
ao
r
tic r
e
g
u
rg
itatio
n. Th
e d
i
agno
si
s is
mad
e
b
a
sed
on
Rev
i
sed
G
h
en
t cr
iter
i
a f
o
r
th
e d
i
agnosis o
f
Marfan
syndrome (MFS) and
related
co
nd
itio
n
s
[2
].
2.
CASE PRESE
N
TATION
A 2
2
y
ear
ol
d
In
di
an m
a
l
e
pr
esent
e
d t
o
o
u
r
hos
pi
t
a
l
w
i
t
h
c
o
m
p
l
a
i
n
t
s
of ri
ght
l
o
i
n
pai
n
si
nce 3
wee
k
s
and
fe
ver si
nce
2 we
eks
.
Hi
s
past
an
d
pers
o
n
al
hi
st
o
r
y
wa
s i
n
si
g
n
i
f
i
cant
,
but
hi
s m
o
t
h
er ha
d s
u
dde
n
d
eat
h at
t
h
e age
o
f
39
y
ears
due
t
o
a
n
un
di
ag
n
o
se
d c
a
rdi
ac
pr
o
b
lem. On
g
e
n
e
ral ex
am
in
atio
n
,
he was lean
, tall
an
d th
e
bui
l
d
of t
h
e p
a
t
i
e
nt
i
s
ect
om
orph as s
h
o
w
n i
n
(Fi
g
u
r
e
1).
Hi
s hei
g
h
t
was 1
77cm
,
wei
g
ht
4
4
k
g
and t
h
e
cal
cul
a
t
e
d B
M
I 1
3
.
7
2 (
kg/
m
2
).
He has
l
o
ng
arm
s
and l
o
ng
sl
ende
r fi
nge
rs
(arac
h
n
o
d
act
y
l
y
)
prese
n
t
.
Hi
s arm
sp
an
to
to
tal h
e
ig
h
t
ratio
-1
.10
(>1.05), m
e
e
t
s th
e MFS
di
agn
o
st
i
c
cri
t
e
ri
a.Hi
s U
ppe
rse
g
m
e
nt
l
e
ngt
h-
8
0
cm
s,
Lower
seg
m
en
t len
g
t
h
-
9
7
c
m
s
, US/LS
ratio
-0
.8
2 (<0
.
85
).
Th
ere is
p
o
sitiv
e thu
m
b
signo
r Steinb
erg
si
g
n
as
sh
own
in
(Figure 2
)
and
po
sitiv
e wrist
sig
n
or walk
er sign
as sh
own
in
(Fi
g
ure 3).
On
exa
m
in
atio
n
o
f
h
i
s o
r
al
cav
ity h
i
g
h
arch
ed
p
a
late was p
r
esen
tas sh
own
in
(F
igure 4). Th
ere are
m
u
ltip
le h
y
p
o
p
i
g
m
en
ted
macu
les
ove
r
t
h
e han
d
s as
sh
o
w
n
i
n
Fi
gu
res 3,
4
an
d al
so on
f
oot
o
f
t
h
e
pat
i
e
nt
.
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IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
269 – 274
27
0
On exam
ination the
tem
p
erature
was
37.7
o
C
,
t
h
e pul
se 1
0
2
beat
s pe
r m
i
nut
e,
t
h
e bl
oo
d pre
ssu
re
1
1
0
/
70
mm H
g
, th
e r
e
sp
ir
at
o
r
y r
a
te 20
breath
s
p
e
r
m
i
n
u
t
e an
d
the oxyg
en
satur
a
tion
98
% w
ith
roo
m
a
i
r
.
Card
io v
a
scu
l
ar system
ic e
x
am
in
atio
n
rev
ealed
a m
i
d
systo
lic click
with
a late systo
lic m
u
rm
u
r
o
n
au
scu
ltatio
n
.
Th
ere was tend
ern
e
ssov
er th
e
rig
h
t
lo
i
n
o
f
th
e p
a
tien
t
.
Fi
gu
re
1.
S
h
o
w
i
ng t
a
l
l
a
n
d
l
ean
pat
i
e
nt
wi
t
h
an
ect
om
orph
b
u
i
l
d
a
n
d
hy
po
pi
g
m
ent
e
d m
acul
e
s
ove
r fo
re
a
r
m
Fi
gu
re
2.
S
h
o
w
i
ng t
hum
b cr
os
si
ng
t
h
e
ul
na
r
boa
r
d
er
o
f
t
h
e ha
n
d
,
t
h
e
Th
um
b si
gn
o
r
St
ei
nbe
rg
si
g
n
Figu
re
3.
This
im
age sh
ows
the
Walke
r-M
u
r
d
o
c
h
(
Wri
st
) si
gn
. T
h
e si
gn
i
s
de
fi
n
e
d as
o
v
erl
a
p
o
f
t
h
e
distal phalange
s of the
th
um
b and
fi
ft
h
fi
n
g
er
w
h
en
en
circling
th
e
o
ppo
site wrist.
It is ind
i
cativ
e
o
f
ar
achno
d
actyly or
ab
no
r
m
ally
lo
ng
an
d slender
fin
g
ers
Fi
gu
re
4.
S
h
o
w
i
ng
Hi
g
h
a
r
c
h
e
d
pal
a
t
e
i
n
t
h
i
s
M
FS pat
i
e
nt
Fi
gu
re
5.
sh
o
w
s a s
upe
ri
o
r
a
n
d
nasal
s
ubl
ux
at
i
on
of
len
s
in th
e left
eye( Ectop
i
a Len
tis presen
t),
o
n
slit
la
m
p
exam
ination
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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PH
S I
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2-8
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0
6
A Case
Report
of M
a
rfan
Syndrome with
Litera
tu
re Review
(Hema
n
t
h
K
u
ma
r Ka
lla
)
27
1
In our
prese
n
t
case there
was no
docum
e
nted fam
i
ly
hi
st
ory
of
M
F
S
,
Ect
o
pi
a Le
nt
i
s
(EL
)
was
prese
n
t, t
h
e Z
s
c
ore
was
3.85
( Ao ,
Z
≥
2)
and with
a systemic
score of
5 (>
7)
.
Tabl
e
1.
S
h
o
w
s Lab
o
r
at
ory
d
a
t
a
of
t
h
e
pat
i
e
nt
o
n
t
h
e
day
o
f
a
d
m
i
ssi
on
Variable
Reference Range
Our Ad
m
i
ssion,
T
h
is
Hospital
Hem
oglobin(
g/dl)
13.
5-
17.
5
12.
8
He
m
a
toc
r
it(%
)
41-
53.
0
44
W
h
ite cell count(
%
)
4500-
1
300
0
12,
200
Differ
e
ntial count(
%
)
Neutr
ophils
40-
62
52
L
y
m
phocy
t
es
27-
40
35
M
onocy
t
es
4-
11
8
E
o
sinophils
0-
8
5
Basophils
0-
3
0
Platelet count(
per
m
m
3
) 1,
50,
000-
4,
0
0
,
000
2,
15,
000
E
r
y
t
hr
ocy
t
e sedim
e
ntation r
a
te(
m
m
/
h
r
)
0-
15
18
Rheu
m
a
toid factor(
I
U
/
m
l)
<30
<30
HIV-1 and
HIV
-
2 antibodies
Non Reactive
Non Reactive
C- Reactive protei
n (m
g/lite
r)
<10
12
B
a
sed o
n
t
h
e h
i
st
ory
of
ri
g
h
t
l
o
i
n
pai
n
f
o
r
3 week
s an
d fe
v
e
r fo
r 2
week
s t
h
e pat
i
e
nt
was
sub
j
ect
ed t
o
t
h
e f
o
l
l
o
wi
n
g
l
a
bo
rat
o
ry
i
n
ve
st
i
g
at
i
ons t
o
e
x
cl
ude
re
nal
pat
hol
ogy
.
Fi
gu
re
6.
S
h
o
w
s ech
ocar
di
o
g
r
am
i
n
pa
rast
er
nal
l
o
ng
axi
s
vi
ew, t
h
e a
o
rt
i
c
r
oot
(
A
o
) diam
e
t
er
measuring
4.02 cm
as m
a
rked a
b
ove
Fi
gu
re
7.
S
h
o
w
s ech
ocar
di
o
g
r
am
i
n
f
o
u
r
c
h
a
m
ber vi
ew
wi
t
h
M
i
t
r
al
va
vl
e
pr
ol
apse
Evaluation Warning : The document was created with Spire.PDF for Python.
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IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
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27
2
Tabl
e
2.
Sh
o
w
s B
i
ochem
i
st
ry re
po
rt
o
f
t
h
e
p
a
t
i
e
nt
on
t
h
e
da
y
of
adm
i
ssi
on
Variable
Reference Range
Our Ad
m
i
ssion,
T
h
is
Hospital
Fasting Blood Glu
c
ose(m
g
/dl)
75-
100
84
2 Hour
or
al glucose toler
a
nce test (
m
g/dl)
<200 110
Sodiu
m
(
m
m
o
l/L
)
136-
14
6
134
Potassiu
m
(mm
o
l/L
)
3.
5-
5 4
Chloride (mm
o
l/
L)
102-
10
9
104
Blood ur
ea(m
g
/dl)
7-
20
17
Seru
m
creatinine(m
g
/dl
)
0.
5-
1.
5
0.
99
The l
a
bo
rat
o
r
y
dat
a
do
ne
on
t
h
e
day
o
f
a
d
m
i
ssi
on as sh
o
w
n
i
n
T
a
bl
e 1
s
h
o
w
s
an
el
evat
e
d
Ery
t
hr
ocy
t
e se
di
m
e
nt
at
i
on rat
e
(E
SR
) a
n
d C
-
R
eact
i
v
e
pr
ot
ei
n. T
h
e
Whi
t
e
cel
l
co
unt
was
i
n
t
h
e
u
ppe
r l
i
m
i
t
as
sh
own
in
Tab
l
e 1
.
Th
e
b
i
o
c
he
m
i
cal an
alysi
s
as shown in Tab
l
e
2
sh
owed
n
o
abn
o
rmality. Urin
e analysis
sho
w
e
d
m
i
crosco
pi
c hem
a
t
u
ri
a an
d py
uri
a
. Lat
e
r
uri
n
e
cul
t
u
re s
h
owe
d
t
h
e
gr
o
w
t
h
of E
s
che
r
i
c
hi
a
col
i
or
ga
ni
sm
s. Next
t
h
e
pat
i
e
nt
was s
u
bject
e
d
t
o
C
T
-Ki
dney
,
Uret
er
s, B
l
ad
d
e
r (
K
UB
)
pl
ai
n
st
u
d
y
(Fi
g
u
r
e
8)
.
Th
e CT-KU
B
PLAI
N
STUDY
of
th
e
p
a
tient sh
ow
ed
m
ild
r
i
gh
t h
ydr
our
eter
on
ep
hr
osis seco
nd
ar
y to
di
st
al
uret
eri
c
(3m
m
) and V
U
J cal
i
c
ul
i
(6
m
m
)
obst
r
uct
i
on as s
h
o
w
n i
n
(Fi
g
u
r
e 8
)
.
Fi
nal
l
y
t
h
e pat
i
e
nt
was
di
ag
no
sed
wi
t
h
M
a
rfa
n
Sy
n
d
r
o
m
e
and
ri
g
h
t
hy
d
r
o
u
ret
e
ro
ne
oh
r
o
si
s.
3.
TREAT
M
ENT
On
t
h
e
day
o
f
adm
i
ssi
on t
h
e
pat
i
e
nt
wa
s p
u
t
on
anal
gesi
cs
fo
r
pr
o
p
er
pai
n
m
a
nagem
e
nt. A
f
t
e
r t
h
e
d
i
agn
o
sis o
f
MFS with
right h
y
d
r
oureteron
ephro
s
is wa
s mad
e
, en
do
card
itis p
r
oph
ylaxis was started
an
d
h
e
was re
ferred t
o
urol
ogy de
partm
e
nt.The patient ha
d undergone
ureteral sten
t placement and rec
ove
re
d
sym
p
t
o
m
a
t
i
call
y
. He was refer
r
ed ba
ck t
o
t
h
e depart
m
e
nt
of I
n
t
e
r
n
al
M
e
di
ci
ne fo
r fu
rt
he
r m
a
nagem
e
nt
rega
rdi
n
g
M
F
S. T
h
e
pat
i
e
nt
was st
art
e
d
on
β
-bloc
k
er therapy whic
h currently rem
a
ins the standa
rd
of ca
re
[3]
. A
s
t
h
e pa
t
i
e
nt
has m
oderat
e
aort
i
c
di
l
a
t
a
t
i
on of
3.
8
5
cm
s (<5cm
s
),
bot
h sh
ort
-
t
e
r
m
and l
o
n
g
-
t
e
rm
β
-
bl
oc
kade i
m
prove
s aort
i
c
st
i
f
f
n
ess i
n
dex a
nd el
ast
i
c
i
t
y
in pat
i
e
nt
s wi
t
h
m
odest
di
l
a
t
a
t
i
on o
r
l
e
ss, [
4
]
,
[
5
]
a
b
e
n
e
fit no
t ob
serv
ed
in
p
a
tien
t
s with
mark
ed
d
ilatatio
n
[6
]
. Ou
r
p
a
tien
t
was clinically asy
m
p
t
o
m
at
ic
pert
ai
ni
ng t
o
c
a
rdi
ovasc
ul
ar
s
y
st
em
.The pat
i
e
nt
i
s
ad
vi
sed
reg
a
rd
ing
m
o
d
e
rate
restriction
o
f
ph
ysical
activ
ity.
Annual eval
uat
i
on
was
offe
re
d to clinically
evaluate a
n
d al
so
w
ith ec
hoca
rdi
o
graphy.
Fi
gu
re
8.
S
h
o
w
s C
T
-
KUB
PL
AI
N S
T
U
D
Y
o
f
t
h
e
pat
i
e
nt
wi
t
h
m
i
l
d
hy
d
r
ou
ret
e
ro
ne
ph
r
o
si
s
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
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S I
S
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:
225
2-8
8
0
6
A Case
Report
of M
a
rfan
Syndrome with
Litera
tu
re Review
(Hema
n
t
h
K
u
ma
r Ka
lla
)
27
3
4.
DIS
C
USSI
ON
M
o
st
pat
i
e
nt
s wh
o ha
ve M
a
r
f
an sy
n
d
r
o
m
e
are us
ual
l
y
di
ag
nos
ed i
n
ci
dent
al
l
y
when t
h
ey
prese
n
t
fo
r a
rou
tin
e ph
ysical ex
a
m
in
atio
n fo
r v
a
riou
s reaso
n
s. As so
in
o
u
r case th
e p
a
tien
t
co
n
s
u
lted fo
r th
e sym
p
to
m
s
o
f
ri
g
h
t
l
o
i
n
pai
n
and fe
ve
r, f
o
r
whi
c
h he wa
s
di
ag
nose
d
in
it
ially with
MF
S.In
ou
r
p
r
esen
t case th
ere
was no
doc
um
ent
e
d fa
m
i
ly
hi
st
ory
of
M
FS, t
h
e Z score
was 3
.
8
5
( A
o
,
Z
≥
2
)
with
Ecto
p
i
a Lentis(EL) and
syste
m
ic
score
o
f
o
n
l
y
5.
Acc
o
r
d
i
n
g t
o
t
h
e
R
e
vi
se
d
Ghe
n
t
c
r
i
t
e
ri
a
fo
r t
h
e
di
a
g
n
o
s
i
s
of
M
F
S
a s
y
st
em
i
c
score
of >
7
i
ndi
cat
es sy
st
em
i
c
i
nvol
vem
e
nt
. T
h
e sy
st
em
i
c
score o
f
5 i
n
ou
r p
r
ese
n
t
case i
s
cal
cul
a
t
e
d ba
sed
o
n
t
h
e
follo
win
g
fin
d
ings:
▪
Po
sitiv
e
Wrist AND t
h
u
m
b
sig
n
–3
(Figu
r
es 2
and
3
)
,
▪
Mitral v
a
lv
e
p
r
o
l
ap
se (all typ
e
s) –1
(Fi
g
ure 7)
▪
R
e
duc
ed
US/
L
S A
N
D
i
n
cre
a
sed a
r
m
/
hei
g
h
t
AN
D
n
o
se
ve
re sc
ol
i
o
si
s
–1
A diagnosis of
MFS
without
system
ic
involvem
e
nt was
m
a
de accordi
n
g to the
“Revised Ghe
n
t
criteria”, in the
abse
nce
of a
fa
m
i
ly history:
Ao
(
Z
≥
2
)
AN
D EL
= M
F
S
[
2
]
.
A com
p
l
e
t
e
descri
pt
i
o
n of R
e
vi
sed G
h
e
n
t
cr
i
t
e
ri
a for t
h
e di
agn
o
si
s o
f
M
a
r
f
an sy
n
d
r
o
m
e
(M
FS) a
nd
rel
a
t
e
d
c
o
n
d
i
t
i
ons
i
s
gi
ve
n
i
n
t
h
e
f
o
l
l
o
wi
n
g
Tabl
e 3. O
u
r di
agn
o
si
s was
m
a
de base
d on
t
h
e
a
b
o
v
e
c
r
i
t
e
r
i
a.
Tab
l
e 3
.
Rev
i
sed
G
h
en
t for
the
d
i
agno
sis o
f
Marfan
syndrome (MFS) and
related
co
nd
itio
n
s
[2
]
In the absence of
a f
a
m
ily history:
(1
) Ao
(
Z
≥
2
)
AN
D E
L
=
MFS
(2
) Ao
(
Z
≥
2
)
AN
D
FB
N1
= MFS
(3
) Ao
(
Z
≥
2
)
AN
D Syst
(
≥
7 points)
= M
F
S
a
(4
) E
L
A
ND
FBN
1
with known Ao = M
F
S
E
L
with or
without Sy
st
AND with an
FBN1
not known with Ao or
no
FBN1
= ELS
Ao (
Z <
2)
AND
S
y
st (
≥
5
)
with at least one skeletal featur
e without E
L
=
M
A
SS
MVP
AND
Ao (
Z <
2)
AND Sy
st (
>
5
)
without E
L
=
MVPS
In the presence of
a f
a
m
i
l
y
history:
(
5
)
EL
AND FH of M
F
S (
a
s defined above)
= M
F
S
(6
) S
y
st (
≥
7 points)
AND FH of M
F
S (
a
s defined above)
=
M
F
S
(7
) Ao
(
Z
≥
2
above 20 y
e
ar
s old,
≥
3
below 20 y
ear
s
)
+
FH of M
FS
(
a
s defined above)
= M
F
Sa
Sy
ste
m
ic score
▪
W
r
ist AND thu
m
b sign –3 (
W
r
i
st OR thu
m
b sign –1)
▪
Pectus carinatu
m
def
o
r
m
it
y –2 (pe
c
t
us excavatu
m
or c
h
est asy
m
m
e
t
r
y –1)
▪
Hindf
oot def
o
rm
ity
–2 (
p
lain pes planus –1)
▪
Pneu
m
o
thor
ax –2
▪
Dural ectasia
–2
▪
Protrusio acetabuli –2
▪
Reduced US/LS
AND incr
eased ar
m
/
h
e
ight AND
no severe scoliosis –1
▪
Scoliosis or
thor
acolu
m
b
ar ky
phosis –1
▪
Reduced elbow extension –
1
▪
Facial featur
es (
3
/5)
–1 (
dolichocep
haly
,
enophtalm
o
s, downs
lanting palp
ebr
a
l fissur
e
s,
m
a
lar
hy
oplasia, r
e
tr
ognathia)
▪
Skin striae –1
▪
M
y
opia > 3 diopter
s –1
▪
M
itr
al valve pr
olapse (
a
ll ty
pes)
–1
M
a
xim
u
m
total: 2
0
points; scor
e
≥
7 indicates sy
ste
m
ic
involvem
e
nt.
Ao,
aor
tic dia
m
eter
at the sinuses of Valsalva above indicated
Z
-
s
cor
e
or
aor
tic r
oot dissection; E
L
,
ectopia lentis; E
L
S
,
ectopia lentis sy
ndr
o
m
e;
FBN1
, fibril
lin-1
m
u
tation;
FB
N1
not known wit
h
Ao,
FBN1
m
u
tation that has not pr
eviously
been
associated with aor
tic root aneurys
m
/
d
issection;
FBN1
with known Ao,
FB
N1
m
u
tation that
has been
identified in an
individual with aortic aneurys
m
; F
H
,
fa
m
i
ly
history
;
MASS,
m
y
opia,
m
itral valve pr
olapse,
bor
der
line
(
Z
<
2)
aor
tic
r
oot
dilation,
skeletal findings,
str
i
ae; M
F
S,
Mar
f
an sy
ndr
om
e;
M
V
PS,
m
itr
al
valve pr
olapse sy
ndr
o
m
e; S
y
st, s
y
ste
m
i
c
score;
US/LS, upper segm
e
n
t/lower seg
m
e
n
t ratio;
Z
,
Z
-sco
re
.
a
Caveat: without discr
i
m
i
nating features
of Shpr
intzen-
G
oldber
g
sy
ndr
o
m
e
(
S
GS),
L
o
ey
s-Dietz sy
ndr
o
m
e (L
DS) or
vascular
Eh
lers-Dan
lo
s s
y
n
d
r
o
m
e (v
E
D
S)
AN
D af
ter
T
G
FB
R1
/2
,
collagen biochem
i
str
y
,
COL3A1
testing if indicated.
Other
conditions/
g
enes
will e
m
erge
with ti
m
e
.
Mo
re th
an
9
0
% o
f
p
a
tien
t
s classified
as h
a
v
i
ng
MFS
h
a
ve a
m
u
tatio
n
in
th
e
g
e
n
e
en
co
d
i
n
g
fibrillin
(
F
BN1
,
chr
o
m
o
so
m
e
1
5q1
5–2
1.3)
[7
], a
g
l
yco
p
r
o
tein
t
h
at
is an
in
teg
r
al
p
a
rt
o
f
t
h
e connective tissue i
n
the
bo
dy
.
A
l
s
o
,
a few M
FS pat
i
e
nt
s wi
t
h
out
m
u
t
a
t
i
ons i
n
t
h
e
FB
N1 ge
ne h
a
ve m
u
t
a
ti
ons
i
n
t
h
e gene
fo
r
TGF-
β
recept
o
r 2 (T
GF
β
R2
).
TG
F-
β
was im
p
lic
ated
in MFS
fo
llowing
recen
t
o
b
s
erv
a
tio
n of its
d
y
sregu
l
ated
sig
n
a
ling
in fi
b
r
illin
-1
d
e
fici
en
t m
i
ce wh
ereb
y an
tag
o
n
i
st
s of TGF-
β
de
creased apoptosis and resc
ue
d lung
defects [8].
T
h
e
hi
g
h
l
e
vel
s
of
ci
rc
ul
at
i
ngT
GF-
β
in
M
FS p
a
tien
t
s [9
], wh
ich in
ci
d
e
n
t
ally am
e
l
i
o
rated
following trea
tm
ent with losa
rtan (an
angiotensin II recep
tor bl
ocker; ARB wit
h
TGF-
β
an
tago
n
i
stic
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
SN
:
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252
-88
06
IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
269 – 274
27
4
pr
o
p
ert
i
e
s) [
1
0]
, t
hus s
u
pp
ort
i
n
g T
G
F-
β
as a th
erap
eu
tic targ
et and
po
ten
tial b
i
o
m
ark
e
r fo
r
MFS. So
t
r
eatm
e
nt
of
M
FS
wi
t
h
l
o
sart
a
n
a
ppea
r
s
t
o
be
p
r
om
i
s
i
ng
bas
e
d
on
st
u
d
i
e
s i
n
a
n
i
m
al
m
odel
s
an
d i
s
u
nde
r
goi
ng
clin
ical trails.
5.
CO
NCL
USI
O
N
M
o
st
pat
i
e
nt
s wh
o ha
ve M
a
r
f
an sy
n
d
r
o
m
e
are us
ual
l
y
di
ag
nos
ed i
n
ci
dent
al
l
y
when t
h
ey
prese
n
t
fo
r a
ro
ut
i
n
e
phy
si
c
a
l
exam
i
n
at
i
on fo
r
vari
ous
re
aso
n
s. T
h
i
s
cas
e rep
o
r
t
b
r
i
n
gs
fo
rt
h t
h
e
revi
e
w
of
vari
ou
s cl
i
n
i
cal
si
gns
of M
FS,
i
t
s
di
agno
si
s b
a
sed o
n
t
h
e R
e
vi
sed G
h
e
n
t
cri
t
e
ri
a, i
t
s
m
a
nagem
e
nt
and t
h
e associ
at
ed co
m
o
rbi
d
co
nd
itio
ns.
CONFLICT
OF
INTEREST
The a
u
t
h
or
s re
po
rt
no
rel
a
t
i
o
nshi
ps t
h
at
co
u
l
d be
co
nst
r
ue
d
as a c
o
nfl
i
c
t
o
f
i
n
t
e
re
st
.
REFERE
NC
ES
[1]
HC. Dietz, GR.
Cutting, RE
. P
y
erit
z, CL
. M
a
s
l
e
n
, LY. S
a
kai
,
GM
. Cors
on, et al
., “
M
arfan s
y
ndr
om
e caus
e
d b
y
a
recurren
t
d
e
nov
o missense mutation in
th
e f
i
brillin gen
e
”,
Nature
, vol. 352
, pp
. 33
7–339, 1991
.
[2]
L
o
ey
s
BL.
,
et
al
.,
J Me
d Ge
net
,
v
o
l. 47
, pp
. 476-4
85,
2010
. doi:10.1136/jmg.2009.072785.
[3]
P
y
eritz R
E
., “Marfan s
y
ndrome
and re
lated disor
d
ers”, In
: Rimoin DL., Connor
JM., P
y
eritz RE., Korf BR.,
eds.,
Em
er
y
and Rim
o
in’s Principles
and Practi
ce of
Medica
l Genet
i
c
s
”, 5th ed
. Lond
on, UK, Church
ill L
i
vingstone
,
vol 3, pp. 3579–
3624, 2007
.
[4]
Groenink M., D
e
Roos A., Muld
er BJM.,
Spaan
JAE., VanDerW
a
ll E
E
.
,
“
C
hange
s in aorti
c
disten
sibilit
y
and puls
e
wa
ve
ve
loc
i
ty
a
sse
sse
d with
magnetic resonance imaging followin
g
beta-b
locker
th
erap
y in
the M
a
r
f
an s
y
ndrom
e”
,
Am J Cardio
l,
vo
l
.
8
2
,
pp.
203
–
2
08, 1998
.
[5]
Rios AS., Silber
EN., Bavishi N., Varga P., Burt
on BK., C
l
ark
WA., Denes P.,
“Effect of
long-
term
β
-blockade
on
aortic root comp
lian
ce
in p
a
tients
with Marf
an s
yndrome”,
Am
H
e
ar
t J.
,
vo
l. 137,
pp.
1057
–
1061
, 1999.
[6]
Y
i
n F
C
P
., Brin
K
P
., Ting
CT
.,
P
y
eri
t
z
RE.
,
“
A
rt
erial h
e
mod
y
namic index
e
s in
Marfan’s s
y
ndro
m
e”,
C
i
rc
ul
a
t
i
on,
vol. 79
, pp
. 854–
862, 1989
.
[7]
P
y
eri
t
z RE
., “
D
isorders of fibrillins and m
i
crofibriloge
n
e
sis: m
a
rfan s
y
ndrom
e
,
MASS phenotype, Contra
ctur
al
arachnod
act
y
l
y
and rel
a
t
e
d cond
itions”, In: R
i
m
o
in DL.,
Connor
JM., P
y
erit
z R
E
., edi
t
ors, “Em
e
r
y
and R
i
m
o
in’s
principles and
pr
actice of medica
l gen
e
tics”, 3rd
ed, New York
, C
hurchill Livingstone, pp
. 1027–6
6, 1997
.
[8]
ER. N
e
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