SYNDROMES PRESENTING ADDUCTED THUMB …...159 GENETIC COUNSELING, Vol. 25, No 2, 2014, pp 159-168...
Transcript of SYNDROMES PRESENTING ADDUCTED THUMB …...159 GENETIC COUNSELING, Vol. 25, No 2, 2014, pp 159-168...
159
GENETIC COUNSELING, Vol. 25, No 2, 2014, pp 159-168
SYNDROMES PRESENTING ADDUCTED THUMB WITH/WITHOUT CLUBFOOT AND DUNDAR SYNDROME
BY A. SUBASIOGLU UZAK 1, J.P. FRYNS 2 AND M. DUNDAR 1
(1) Department of Medical Genetics, Erciyes University School of Medicine, Kayseri, Turkey.(2) Departments of Human Genetics, Catholic University of Leuven, Leuven, Belgium.
INTRODUCTION
A congenital flexed adducted thumb has been called variously as con-genital clasped thumb, thumb in palm deformity or flexion adduction deformity of the thumb. This condition can be an isolated anomaly or associated with several genetic disorders. Congenital clasped thumb refers to a wide spectrum of thumb anomalies. It can be a result of mild deficiencies of the thumb extensor mechanism (extensor pollicis brevis or longus or both) or severe abnormalities of the extrinsic and intrinsic muscles, web space and soft tissue and joint contractures (3). According to the most useful classification that proposed; type 1 is supple clasped thumb with absence of hypoplasia of the extensor mus-cles, the thumb can passively abducted and this condition is seen with-out other digital abnormalities. Type II clasped thumb is a complex type with additional findings of hand contractures as joint contractures and collateral ligament abnormalities. In this form the thumb cannot be passively abducted and extended. Also other digital anomalies can be seen. Type III clasped thumb is associated with related syndromes especially arthrogryposis group. In this type the extensor mechanism can be deficient or normal (17, 20, 28). This condition should alert the
Summary: Syndromes presenting adducted thumb with/without clubfoot and Dundar syndrome: Congenital adducted thumb has been called variously as congenital clasped thumb, thumb in palm deformity or flexion adduction deformity of the thumb. This condition can be an isolated anomaly or associated with several genetic disorders. The syndromes that include adducted thumb as a cardinal feature such as Dundar Syndrome are few in the literature. This syndrome is an autosomal-recessive very rare disorder characterized by typical facial appearance with dysmorphic features that includes wasted build, hyperextensible, thin and translucent skin with atrophic scarring, severe congenital contractures of fingers and thumbs, club feet, severe kyphoscoliosis, joint instability, muscular hypotonia, and ocular involvement. Heart, kidney, and/or intestinal defects can also be observed. Up to date the syndrome is described in few families in the literature. Here we discuss the syndromes that include adducted thumb as a cardinal feature and also the differential diagnosis of the Dundar Syndrome according to the literature.
Key-words: Adducted thumb - Adducted thumb-clubfoot syndrome - Dundar syndrome - Ehlers-Danlos syndrome musculocontractural type.
160
GENETIC COUNSELING
clinician for various genetic syndromes (30).Dundar Syndrome (Ehlers-Danlos Syndrome, Musculocontractural Type), Christian Adducted Thumbs Syndrome, Escobar or multiple pterygia syndrome, MASA Syndrome, Arthrogryposis Multiplex Con-genita, Distal, Type I, Arthrogryposis, Distal, Type 2a are some of the most common syndromes that include adducted thumb as a cardinal feature.
SYNDROMES
Dundar Syndrome (Ehlers-Danlos Syndrome, Musculocontractural Type, Adducted Thumb – Club Foot Syndrome, Arthrogryposis, Dis-tal, with Peculiar Faces and Hydronephrosis, MIM ID #601776) is a rare syndrome that was originally described by Dundar et al. in male and female first cousins (4). Later on Sonoda and Kouno and Janecke et al. reported similar cases (10, 26). Up to date there are few reports published related with the syndrome. This syndrome embraces a broad spectrum of features. It is characterized by typical facial appearance that comprises frontal bossing, late-closing anterior fontanelle, tele-canthus, downslanting palpebral fissures and deep set/ posteriorly ro-tated ears, downturned angles of mouth, facial clefting. The dysmor-phic features include wasted build, thin and translucent skin, ocular anterior chamber abnormalities, distal arthrogryposis with arachnodac-tyly and adducted thumbs, club feet, joint instability and coagulopathy. The heart, kidney, and/or intestinal defects can also be observed (4, 5). Dundar et al. performed a genome-wide linkage scan, sequenced two candidate genes on chromosome 15q15, and identified homozygous mutations in the CHST14 gene in each family (5). The CHST14 gene encodes N-acetylgalactosamine 4-O-sulfotransferase 1 (D4ST1), which catalyzes the 4-O-sulfation of N-acetylgalactosamine (Gal-NAc) residues in dermatan sulfate and it is determined that loss of der-matan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome. Later on Müller et al. demonstrated locus heterogeneity in the syndrome (23). They provided evidence for the important role of dermatan sulfate in human development besides extracellular matrix maintenance (23). As a result the syndrome is the first metabolic de-fect specific (restricted) to dermatan sulfate biosynthesis and it is a form of congenital disorder of glycosylation (9). Miyake et al. demon-strated abnormal collagen bundle formation at a group of patients and suggested that this can be a main pathology associated with a decorin glycosaminoglycan abnormality (21). Dundar Syndrome has an auto-somal recessive inheritance pattern and is caused by homozygous or
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compound heterozygous mutations (5). To date nine CHST14 variants have been determined which are all related with the syndrome (5, 14, 16, 18, 21).
Adducted Thumbs Syndrome (Thumbs, Congenital Clasped, MIM ID 201550) that characterized by arthrogryposis, dysmyelination, cra-niostenosis, and cleft palate. The syndrome was originally described by Christian et al. in three infants from an inbred Amish pedigree and consisting of adducted thumbs, craniosynostosis and severe neurolog-ical abnormalities (2). Striking dysmorphic features include prominent sutures, a prominent occiput, telecanthus, an antimongoloid eye slant, strabismus, a narrow, high, or cleft palate with a bifid uvula, posteriorly rotated ears, and micrognathia. There are multiple joint contractures of the large joints, but also of the index fingers, in addition to the adduct-ed thumbs. Muscle bulk was reduced and the infants were hypotonic (2). Kunze et al. reported a similar female infant who died at the age of 3 months. She had difficulty in swallowing with an ophthalmoplegia, hypotonia, and areflexia. There were multiple joint contractures with camptodactyly and adducted thumbs, but apparently no craniosynos-tosis (15). The genetic basis of this syndrome remains unknown but it was observed to have an autosomal recessive inheritance pattern.
Multiple pterygia syndrome (MIM ID 265000) is a form of arthro-gryposis multiplex congenita which is an autosomal recessive condi-tion and shows clinical heterogeneity. Initially it is categorized into two types; prenatally lethal and nonlethal (22). The nonlethal type, called Escobar syndrome (ES) (MIM #265000) characterized by ex-cessive webbing (pterygia, especially of the neck, antecubital and pop-liteal areas), congenital joint contractures (arthrogryposis), scoliosis, syndactyly and camptodactyly of the fingers, and foot deformities (2, 15). Other variable features include intrauterine death, congenital re-spiratory distress, growth retardation, short stature, kyphoscoliosis and other vertebral anomalies, a mild to moderate degree of facial dysmor-phism, ptosis, antemongoloid slant of eyes, low-set ears, cleft palate, cryptorchism, arachnodactyly and congenital contractures (4, 10, 11, 26). The syndrome was first reported by Bussiere in 1902 and since then, more than 60 families have been reported (11, 13).Hoffmann et al. and Morgan et al. reported that both variants of multi-ple pterygium syndrome can be caused by mutations in the gamma, or fetal, subunit of the nicotinergic acetylcholine receptor (AChR) gene located at chromosome 2q33–q34 (8, 22). Further, it was observed that mutations in two other related genes, CHRND and CHRNA1, also can cause the lethal type of MPS (19).
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GENETIC COUNSELING
MASA Syndrome (Mental Retardation, Aphasia, Shuffling Gait, And Adducted Thumbs, Spastic Paraplegia, Type 1, Clasped Thumb and Mental Retardation, Thumb, Congenital Clasped, With Mental Retardation, Adducted Thumb with Mental Retardation, Gareis-Ma-son Syndrome, Crash Syndrome, MIM ID #303350) was originally described by Bianchine and Lewis (1). The cardinal clinical features of the syndrome are mental retardation, aphasia, shuffling gait, and adducted thumbs was summarized by the acronym MASA (1). The shuffling gait is thought to be caused by spasticity of the lower limbs. The clinical features also include; short stature, microcephaly, macro-cephaly, strabismus, kyphosis, lordosis, pes cavus, talipes equinovarus increased reflexes and the delayed onset of speech. Structural brain abnormalities can also be seen such as agenesis of the corpus callosum, enlarged cerebral ventricles and hydrocephalus (1, 32). The condition has an X-linked recessive inheritance pattern. This syndrome is caused by mutation in the L1 cell adhesion molecule (L1CAM) gene (31).
Arthrogryposis Multiplex Congenita, Distal, Type 1a (MIM ID #108120) belongs to a highly heterogeneous group. In this type the affected parts of the limbs are usually the distal parts especially hands and feet. The fingers are medially overlapping, fists are clenched and also camptodactyly, ulnar deviation of the fingers and the positional foot deformities can be seen. The other joints contractures are variable. In this type of arthrogryposis there are no associated visceral anoma-lies. Besides this, the patients’ intelligence is normal (7). The classic form is always sporadic but there are some authors that described fam-ilies that have dominant inheritance (7, 12). The causative factor of this type of artrogryposis was demonstrated by Sung et al. and TPM2 gene that encodes beta-tropomyosin was determined (27).
Arthrogryposis, Distal, Type 2a (Freeman-Sheldon Syndrome, Whis-tling Face-Windmill Vane Hand Syndrome, Craniocarpotarsal Dys-trophy, Craniocarpotarsal Dysplasia, MIM ID #193700) syndrome is originally described by Freeman and Sheldon (6). The syndrome has an autosomal dominant inheritance pattern and includes skeletal mal-formations and facial characteristics. Abnormal x-ray appearance of the floor of the anterior cranial fossa of the skull, microcephaly, camp-todactyly with ulnar deviation, adducted thumbs, kyphoscoliosis, hip dislocation, talipes equinovarus, contracted toes, and vertical talus; are the common skeletal abnormalities. Facial characteristics include full forehead, mask like facies, deep-set eyes with hypertelorism and tele-canthus, epicanthal folds, increased philtrum length, small nose with
163
hypoplastic alae nasi and a small mouth (6). Toydemir et al. screened 28 FSS probands for mutations in genes that encode myosin heavy chains and a mutation in the MYH3 gene in 26 of 28 FSS cases was reported (29).
DISCUSSION
At the genetic evaluation of a case with adducted thumbs the clini-cian must be careful while making the final decision between non syn-dromic adducted thumbs and syndromic forms (Table I). In a study in which twenty-five patients were included, additional features were observed in 88% of the cases (30). Neurological evaluation must be done carefully as neurologic abnormalities are commonly associat-ed with the condition. Brain imaging should be performed and be-sides mental status should be evaluated (30). Up to date 27 genetic syndromes have been identified in which adducted thumbs can be a possible clinical clue (30). Before the molecular analyses, cytogenetic analyses must be performed as cytogenetic abnormalities such as inter-stitial 1p36 deletion, 2q inverted duplication/ deletion, 3p26 deletion found to be associated with adducted thumbs (30). Dundar syndrome represents a recognizable pattern with generalized connective tissue disorders with facial dysmorphic features. Effected individuals in each of the families shared phenotypic characteristics that are atypical for previously described syndromes such as Christian Adducted Thumbs Syndrome, Escobar or multiple pterygia syndrome, MASA Syndrome, Arthrogryposis Multiplex Congenita, Distal, Type 1a, Arthrogrypo-sis, Distal, Type 2a. With the presence of characteristic features such as typical facial appearance, wasted build, thin and translucent skin, ocular anterior chamber abnormalities, arachnodactyly and distal ar-throgryposis with severely adducted thumbs, club feet, joint instability and coagulopathy, Dundar Syndrome must be investigated by perform-ing molecular analysis for the responsible gene, CHST14 which is on chromosome 15q15. Shimizu et al. presented a comprehensive review of all 20 reported patients (25). They mentioned that, at birth some re-markable features can be seen such as large fontanelle, hypertelorism, downslanting palpebral features, multiple congenital contractures with adducted thumbs, talipes equinovarus, and cylindrical fingers and as the cases grew older spinal deformities, marfanoid body habitus, and recurrent joint dislocations can be seen. Dermatologic features can be remarkable also such as hyperextensibility, and fragility that can cause atrophic scars. Abnormal platelet function which can cause bleeding,
164
GENETIC COUNSELING
Dund
ar sy
ndro
me
Addu
cted t
hum
bs
synd
rom
eM
ultip
le pt
eryg
ia sy
ndro
me,
Esco
bar V
arian
tM
ASA
Synd
rom
eDi
stal a
rthro
gryp
o-sis
type
1ADi
stal a
rthro
gryp
osis
type
2A
OMIM
#60
1776
2015
5026
5000
3033
5010
8120
19
3700
Inhe
ritan
ceAu
tosom
al rec
essiv
eAu
tosom
al rec
essiv
eAu
tosom
al rec
essiv
eX-
linke
d rec
essiv
eAu
tosom
al do
mina
ntAu
tosom
al do
mina
nt
Grow
thSe
verel
y was
ted bu
ildSh
ort s
tatur
eSh
ort s
tatur
eLo
w bir
th we
ight, F
ailur
e to
thrive
(inf
ancy
), Po
st-na
tal gr
owth
defic
iency
Head
and N
eck
Brac
hyce
phaly
, large
fonta
nel w
ith
delay
ed cl
osur
eCr
anios
tenos
is,
micro
ceph
alyNe
ck pt
erygia
Micr
ocep
-ha
ly, m
acro
-ce
phaly
Micr
ocep
haly,
shor
t nec
k
Face
Broa
d, fla
t for
ehea
d, mi
croret
rogn
a-thi
a in i
nfan
cy, p
rotru
ding j
aw fr
om
adole
scen
ce, f
acial
asym
metry
from
ad
olesc
ence
Stiff
, myo
pathi
c fac
iesM
icrog
nathi
a, lon
g phil
trum,
fla
t, exp
ressio
nless
face,
long
face
Full f
oreh
ead,
mask
-like
fac
ies lo
ng ph
iltru
m,
H-sh
aped
chin
dimple
, fla
t fac
e, ‘w
histli
ng’
appe
aranc
eEa
rsLo
w-se
t and
rotat
ed ea
rs, pr
omine
nt ea
rs, he
aring
impa
irmen
tLo
w-se
t ears
, hea
ring l
oss,
cond
uctiv
eEy
esEy
e ano
malie
s, va
riable
, blue
scler
ae,
hype
rtelor
ism, d
owns
lantin
g palp
ebral
fis
sures
, stra
bismu
s, my
opia,
glau
co-
ma, m
icroc
orne
a, ret
inal d
etach
ment,
an
terior
cham
ber a
bnor
malit
y
Ptos
is, do
wnsla
nting
palpe
bral
fissu
res, e
pican
thal f
olds,
hype
rtelor
ism
Strab
ismus
Deep
set e
yes,
telec
ant-
hus,
epica
nthal
folds
, str
abism
us, b
lepha
roph
i-mo
sis, p
tosis
Nose
Shor
t with
hypo
plasti
c colu
mella
, long
ph
iltru
mBr
oad n
asal
bridg
e, sm
all no
se, h
ypop
lastic
ala
e nas
iM
outh
Thin
uppe
r lip,
small
mou
th in
infan
cy,
high-
arche
d pala
te, cl
eft pa
late
Mou
th op
en,
high-
arche
d pala
te,
cleft
palat
e
Down
turne
d cor
ners
of m
outh,
dif
ficult
y in o
penin
g mou
th,
cleft
palat
e, hig
h-arc
hed p
alate,
sm
all m
outh
Small
mou
th, pu
rsed l
ips
Card
iovas
cular
Valve
anom
alies
, atri
al se
ptal d
efect,
he
matom
as, r
ecur
rent la
rge su
bcuta
-ne
ous
Table
I: T
he cl
inica
l fea
tures
of th
e syn
drom
es (s
umma
rized
from
Onli
ne M
ende
lian I
nheri
tance
in M
an, O
MIM
®. M
cKus
ick-N
athan
s Ins
titute
of G
eneti
c Med
icine
, Joh
ns
Hopk
ins U
nivers
ity (B
altim
ore,
MD)
, { U
pdate
d 30 A
ugus
t 201
3 }. W
orld
Wide
Web
URL
: http
://om
im.or
g/).
165
Resp
irato
ryHe
mopn
eumo
thorax
Resp
irator
y ins
uffi-
cienc
yNe
onata
l res
pirato
ry di
stres
s Pu
lmon
ary hy
popla
siaRi
bs, S
ternu
m,
Clav
icles
and
Scap
ulae
Pectu
s exc
avatu
m, fla
t and
thin
pectu
sRi
b fus
ion
Long
clav
icles
Stiff
shou
lders
Brea
stsHy
popla
stic n
ipples
Diap
hrag
mHi
atal h
ernia
Diap
hrag
matic
hern
ia, ev
entra
-tio
n of d
iaphr
agm
Abdo
men
Umbil
ical h
ernia,
dias
tasis
recti
Umbil
ical h
ernia
Gastr
ointes
tinal
Cons
tipati
on, d
iverti
cular
perfo
ra-tio
n, du
oden
al ob
struc
tion d
ue to
ma
lrotat
ion
Swall
owing
diffi
-cu
lties
Geni
tour
inar
yCr
yptor
chidi
sm, h
ydro
neph
rosis
, bil
ateral
, rec
urren
t cys
titis,
enlar
ged
bladd
er
Cryp
torch
idism
, ingu
inal
hern
ia, hy
posp
adias
, abs
ence
of
labia
major
a
Ingu
inal h
ernia
Spin
eSc
olios
isSc
olios
is, ky
phos
is, fu
sion o
f ce
rvica
l vert
ebrae
, ante
rior
clefti
ng of
verte
bral
bodie
s
Kyph
osis,
lor
dosis
Mild
scoli
osis
Kyph
osco
liosis
, spin
a bifi
da oc
culta
Pelvi
sDi
sloca
tion o
f hip
Hip fl
exion
contr
ac-
tures
, con
genit
al hip
dis
locati
ons,
decre
-as
ed hi
p abd
uctio
n
Hip c
ontra
ctures
Lim
bsHy
perm
obili
ty of
shou
lders
Abse
nt pa
tella,
dysp
lastic
pa
tella,
dislo
cated
radia
l hea
d, fle
xion c
ontra
ctures
Elbo
w fle
xion
contr
actur
es, k
nee
flexio
n con
tractu
res
Shou
lder c
ontra
ctures
Kn
ee co
ntrac
tures
Hand
sIn
infan
cy bi
latera
l add
ucted
thum
bs,
arach
noda
ctyly,
slen
der a
nd/or
cylin
d-ric
al fin
gers,
dista
l arth
rogr
ypos
is,
hype
rmob
ility
of sm
all jo
ints
Thum
bs fle
xed a
nd
addu
cted
Camp
todac
tyly,
synd
actyl
y, ara
chno
dacty
lyAd
ducte
d thu
mbs
Tigh
tly cl
ench
ed fis
ts (n
eona
te), c
ampto
-da
ctyly
(adult
), uln
ar de
viatio
n (ad
ult),
abse
nt dis
tal in
ter-
phala
ngea
l crea
ses,
sin
gle tr
ansv
erse
palm
ar cre
ases
Ulna
r dev
iation
, cor
tical
thumb
s, ca
mptod
actyl
y
Feet
Talip
es eq
uinov
arus i
n inf
ancy
, talip
es
valgu
s and
plan
us, p
rogr
essiv
e, hy
per-
mobil
ity of
small
joint
s
Talip
es ca
lcane
ovalg
us, ta
lipes
eq
uinov
arus,
rock
er-bo
ttom
feet, c
ampto
dacty
ly
Pes c
avus
, tal
ipes e
qui-
nova
rus
Talip
es eq
uinov
ar-us
, calc
aneo
valgu
s de
form
ities
, vert
ical
talus
Equin
ovaru
s, co
ntrac
ted
toes,
verti
cal ta
lus
166
GENETIC COUNSELING
Skin
Hype
rexten
sible
skin,
ecch
ymos
es,
fragil
e skin
with
atro
phic
scarr
ing,
delay
ed w
ound
heali
ng, h
ypera
lgesia
to
pres
sure,
palm
ar cre
ases
, fine
to
acro
geria
-like
, sub
cutan
eous
infec
ti-on
s, rec
urren
t, with
fistul
a for
matio
n
Hype
rtrich
osis
Ptery
gia of
digit
s, ne
ck, a
xillae
, an
tecub
ital, p
oplit
eal, i
ntercr
u-ral
area
s
Abse
nt dis
tal in
terp-
halan
geal
creas
es,
single
tran
svers
e pa
lmar
creas
es
Thick
ened
skin
over
flexo
r sur
face o
f pro
ximal
phala
nges
Skin
Hist
ology
Fine
colla
gen fi
bers
pred
omina
nt in
reticu
lar to
papil
lary d
ermis,
thin
colla
gen b
undle
sEl
ectro
n Micr
os-
copy
Colla
gen fi
brils
disp
ersed
in re
ticula
r de
rmis,
smoo
th, ro
und c
ollag
en fib
rils
Mus
cle, S
oft T
issue
Hema
tomas
, rec
urren
t large
subc
utane
-ou
s, low
mus
cle m
ass,
hypo
tonia
Myo
pathy
Redu
ced m
uscle
mas
sM
ild m
uscle
wea
knes
s, sk
eletal
mus
cle bi
opsy
sh
ows fi
ber s
ize va
ria-
bility
; type
1 fib
er typ
e pr
edom
inanc
e, sm
all ty
pe
1 fibe
rs, in
creas
ed in
ter-
stitia
l con
necti
ve tis
sue
Meta
bolic
Fea
ture
sHy
perp
yrex
ia, us
ually
as-
socia
ted w
ith an
esthe
sia,
malig
nant
hype
rtherm
iaNe
urolo
gicGr
oss m
otor d
evelo
pmen
tal de
layDy
smye
linati
-on
with
exce
ss my
elin-
depe
nden
t gli
osis,
mye
lin
solub
iliza
tion,
ge-
neral
ized h
ypoto
nia,
velop
hary
ngea
l ins
uffic
iency
Norm
al int
ellige
nce
Men
tal
retard
ation
, ap
hasia
, sh
uffli
ng
gait,
lower
limb s
pasti
-cit
y, ag
enes
is of
the c
orpu
s ca
llosu
m,
enlar
ged
cereb
ral
ventr
icles
, hy
droc
ep-
halus
Norm
al int
ellige
nce
Men
tal re
tarda
tion,
seizu
res
Mole
cular
Bas
isCH
ST14
, 608
429.0
001
CHRN
G, 10
0730
.0001
L1CA
M,
3088
40.00
04TP
M2,
1909
90.00
01M
YH3,
1607
20.00
01
Table
I: C
ontin
ued
167
REFERENCES
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2. CHRISTIAN J.C., ANDREWS P.A., CONNEALLY P.M., MULLER J.: The adducted thumbs syndrome. An autosomal recessive disease with arthrogrypo-sis, dysmyelination, craniostenosis, and cleft palate. Clin. Genet., 1971, 2, 95-103.
3. COOPER C.: Fundamentals of Hand Therapy: Clin-ical Reasoning and Treatment Guidelines for Com-mon Diagnoses of the Upper Extremity. Elsevier Health Sciences, 2007.
4. DUNDAR M., DEMIRYILMAZ F., DEMIRYILMAZ I., KUMANDAS S., ERKILIC K., KENDIRCI M., TUNCEL M., OZYAZGAN I., TOLMIE J.L.: An autosomal recessive adducted thumb-club foot syn-drome observed in Turkish cousins. Clin. Genet., 1997, 51, 61-64.
5. DUNDAR M., MULLER T., ZHANG Q., PAN J., STEINMANN B., VODOPIUTZ J., GRUBER R., SONODA T., KRABICHLER B., UTERMANN G., BAENZIGER J.U., ZHANG L., JANECKE A.R.: Loss of dermatan-4-sulfotransferase 1 function re-sults in adducted thumb-clubfoot syndrome. Am. J. Hum. Genet., 2009, 85, 873-882.
6. FREEMAN E.A., SHELDON J.H.: Cranio-carpotar-sal dystrophy: undescribed congenital malformation. Arch. Dis. Child., 1938, 13, 277-283.
7. HALL J.G., REED S.D., GREENE G.: The distal arthrogryposes: delineation of new entities--review
and nosologic discussion. Am. J. Hum. Genet., 1982, 11, 185-239.
8. HOFFMANN K., MULLER J.S., STRICKER S., MEGARBANE A., RAJAB A., LINDNER T.H., CO-HEN M., CHOUERY E., ADAIMY L., GHANEM I., DELAGUE V., BOLTSHAUSER E., TALIM B., HORVATH R., ROBINSON P.N., LOCHMÜLLER H., HÜBNER C., MUNDLOS S.: Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am. J. Hum. Genet., 2006, 79, 303-312.
9. JANECKE A.R., BAENZIGER J.U., MULLER T., DUNDAR M.: Loss of dermatan-4-sulfotransferase 1 (D4ST1/CHST14) function represents the first dermatan sulfate biosynthesis defect, “dermatan sul-fate-deficient adducted thumb-clubfoot syndrome”. Hum. Mutat., 2011, 32, 484-485.
10. JANECKE A.R., UNSINN K., KRECZY A., BALD-ISSERA I., GASSNER I., NEU N., UTERMANN G., MULLER T.: Adducted thumb-club foot syndrome in sibs of a consanguineous Austrian family. J. Med. Genet., 2001, 38, 265-269.
11. JONES K.L.: Smith’s Recognizable Patterns of Hu-man Malformation. 5th ed. Philadelphia, WB Saun-ders, 1997.
12. KLEMP P., HALL J.G.: Dominant distal arthrogry-posis in a Maori family with marked variability of expression. Am. J. Hum. Genet., 1995, 55, 414-419.
13. KODAGANUR S.G., TONTANAHAL S.J., SARDA A., SHAH M.H., BHAT V., KUMAR A.: Clinical phe-
congenital cardiac defects, ophthalmological complications, and uro-lithiasis also reported (25).Like all the syndromes early clinical diagnosis will be helpful for pre-diction of prognosis, the assessment of the other clinical problems of the patients and for the follow-up and therapy of the clinical conditions related with the syndrome. It is important to identify the mutation in order to inform the families for prenatal and preimplantation genetic diagnosis and as the syndrome has an autosomal recessive inheritance pattern, detailed genetic counseling must be given to families accord-ing to the literature.
Skin
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sible
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fragil
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phic
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delay
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reticu
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thin
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undle
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ticula
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ollag
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rils
Mus
cle, S
oft T
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mus
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tonia
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pathy
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ced m
uscle
mas
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ild m
uscle
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cle bi
opsy
sh
ows fi
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ize va
ria-
bility
; type
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llosu
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droc
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ellige
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168
GENETIC COUNSELING
notype and the lack of mutations in the CHRNG, CHRND, and CHRNA1 genes in two Indian fam-ilies with Escobar syndrome. Clin. Dysmorphol., 2013, 22, 54-58.
14. KOSHO T., MIYAKE N., HATAMOCHI A., TAKA-HASHI J., KATO H., MIYAHARA T., IGAWA Y., YASUI H., ISHIDA T., ONO K., KOSUDA T., IN-OUE A., KOHYAMA M., HATTORI T., OHASHI H., NISHIMURA G., KAWAMURA R., WAKUI K., FUKUSHIMA Y., MATSUMOTO N.: A new Ehlers-Danlos syndrome with craniofacial charac-teristics, multiple congenital contractures, progres-sive joint and skin laxity, and multisystem fragili-ty-related manifestations. Am. J. Med. Genet., 2010, 152, 1333-1346.
15. KUNZE J., PARK W., HANSEN K.H., HANEFELD F.: Adducted thumb syndrome: report of a new case and a diagnostic approach. Eur. J. Pediatr., 1983, 141, 122-126.
16. MALFAIT F., SYX D., VLUMMENS P., SYMOENS S., NAMPOOTHIRI S., HERMANNS-LE T., VAN LAER L., DE PAEPE A.: Musculocontractural Ehlers-Dan-los syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a sin-gle clinical entity caused by mutations in the der-matan-4-sulfotransferase 1 encoding CHST14 gene. Hum. Mutat., 2010, 31, 1233-1239.
17. MCCARROLL H.R.: Congenital flexion deformities of the thumb. Hand Clin., 1985, 1, 567-575.
18. MENDOZA-LONDONO R., CHITAYAT D., KAHR W. H. A., HINEK A., BLASER S., DUPUIS L., GOH E., BADILLA-PORRAS R., HOWARD A., MITTAZ L., SUPERTI-FURGA A., UNGER S., NISHIMURA G., BONAFE L.: Extracellular matrix and plate-let function in patients with musculocontractural Ehlers-Danlos syndrome caused by mutations in the CHST14 gene. Am. J. Med. Genet., 2012, 158, 1344-1354.
19. MICHALK A., STRICKER S., BECKER J., RUPPS R., PANTZAR T., MIERTUS J., BOTTA G., NARET-TO V. G., JANETZKI C., YAQOOB N., OTT C. E., SEELOW D., WIECZOREK D., FIEBIG B., WIRTH B., HOOPMANN M., WALTHER M., KÖRBER F., BLANKENBURG M., MUNDLOS S., HELLER R., HOFFMANN K.: Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am. J. Hum. Genet., 2008, 82, 464-476.
20. MIH A. D.: Congenital clasped thumb. Hand Clin., 1998, 14, 77–84.
21. MIYAKE N., KOSHO T., MIZUMOTO S., FURUI-CHI T., HATAMOCHI A., NAGASHIMA Y., ARAI E., TAKAHASHI K., KAWAMURA R., WAKUI K., TAKAHASHI J., KATO H., YASUI H., ISHIDA T., OHASHI H., NISHIMURA G., SHIINA M., SAITSU H., TSURUSAKI Y., DOI H., FUKUSHIMA Y., IKE-GAWA S., YAMADA S., SUGAHARA K., MATSU-MOTO N.: Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome. Hum. Mutat., 2010, 31, 966-974.
22. MORGAN N.V., BRUETON L.A., COX P., GREAL-LY M.T., TOLMIE J., PASHA S., ALIGIANIS I.A., VAN BOKHOVEN H., MARTON T., AL-GAZALI L., MORTON J.E., OLEY C., JOHNSON C.A., TREM-BATH R. C., BRUNNER H.G., MAHER E.R.: Muta-tions in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar vari-ants of multiple pterygium syndrome. Am. J. Hum. Genet., 2006, 79, 390-395.
23. MULLER T., MIZUMOTO S., SURESH I., KOMAT-SU Y., VODOPIUTZ J., DUNDAR M., STRAUB V., LINGENHEL A., MELMER A., LECHNER S., ZSCHOCKE J., SUGAHARA K., JANECKE A.R.: Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syn-drome. Hum. Mol. Genet., 2013, 22, 3761-3772.
24. ONLINE MENDELIAN INHERITANCE IN MAN, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), { Updated 30 August 2013 }. World Wide Web URL: http://omim.org/
25. SHIMIZU K., OKAMOTO N., MIYAKE N., TAIRA K., SATO Y., MATSUDA K., AKIMARU N., OHASHI H., WAKUI K., FUKUSHIMA Y., MATSUMOTO N., KOSHO T.: Delineation of dermatan 4-O-sulfotrans-ferase 1 deficient Ehlers-Danlos syndrome: observa-tion of two additional patients and comprehensive review of 20 reported patients. Am. J. Hum. Genet., 2011, 155, 1949-1958.
26. SONODA T., KOUNO K.: Two brothers with distal arthrogryposis, peculiar facial appearance, cleft pal-ate, short stature, hydronephrosis, retentio testis, and normal intelligence: a new type of distal arthrogryp-osis?. Am. J. Hum. Genet., 2000, 91, 280-285.
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ADDRESS FOR CORRESPONDENCE: Munis Dundar, M.D., Ph.D. Erciyes University, School of Medicine Department of Medical Genetics Kayseri, Turkey Phone: 90 352 4370600 E-mail: [email protected]
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29. TOYDEMIR R.M., RUTHERFORD A., WHIT-BY F.G., JORDE L.B., CAREY J.C., BAMSHAD M.J.: Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat. Genet., 2006, 38, 561-565.
30. VERHAGEN J.M., SCHRANDER-STUMPEL C.T., BLEZER M.M., WEBER J.W., SCHRANDER J.J., RUBİO-GOZALBO M.E., BAKKER J.A., STEG-MANN A.P., VOS Y. J., FRINTS S. G.: Adducted thumbs: a clinical clue to genetic diagnosis. Eur. J. Med. Genet., 2013, 56, 153-158.
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