guadalajara camptodactyly syndrome type ii
TRANSCRIPT
Clinical Genetics 1985: 28: 5460
Guadalajara camptodactyly syndrome
J. M. CANTU', D. GARC~A-CRUZI, J . GIL-VIERA~, Z. NAZARA', M. L. RAM~REZ', M. T. SOLE-PUJOL~ AND J. SANCHEZ-CORONA]
'Division de Genetica, Subjefatura de Investigacion Cientifica, Unidad de Investigacion Biomedica, 2Hospital de Pediatria y 'Hospital de Especialidades, Centro Medico de Occidente, Instituto
Mexican0 del Seguro Social, Guadalajara, Jalisco, Mexico
Two sisters and an unrelated girl presented a distinct intrauterine growth retardation-malfor- mation syndrome with short stature, microcephaly, pectus excavatum, hip dislocation, hypo- plastic pubic region and genitalia, camptodactyly, talipes, shortened 2nd toes, hypoplastic patella and skeletal dysplasia probably due to homozygocity from an autosomal recessive gene.
Received 21 August 1984. revised, uccepted fo r publication 11 March 1985
Key words: Camptodactyly; intrauterine growth retardation; mental retardation; patella agenesis/hypoplasia.
In 1906, Landouzy introduced the term camptodactyly to refer to constitutionally crooked digits (Landouzy 1906) due to a permanent flexion contracture of the proxi- mal interphalangeal joints (Temtamy & McKusick 1978). An autosomal dominant form is known and there are about a dozen of inherited malformation disorders that show camptodactyly (Goodman et al. 1972, Cantu et al. 1980, McKusick 1983). The purpose of this report is to describe three cases (two sisters and one unrelated girl) affected by a probably inherited distinct intrauterine growth retardation-malfor- mation syndrome with camptodactyly. An abstract with data from two of the cases has been already published (Cantu et al. 1981, McKusick 1983).
Case Reports
Cuse A : The 5-year-old proposita (Fig. l a and 2a) was the product of the 1st full-term
pregnancy and dystocic (pelvic presen- tation) delivery. Nanosomy, camptodactyly, absence of flexion of the knee and bilateral talipes were noted at birth. Palpebral ptosis, evident at about three months of age, was surgically corrected as later were the talipes. The father and mother, clinically normal and non-consanguineous, were 25 and 23 years of age, respectively, at the proposita's birth. She has two sisters; one normal, aged 4 years, and Case B.
The psychomotor development has been mildly delayed. The somatometric par- ameters are shown in Table 1 and the clini- cal findings in Table 2. As additional fea- tures the patient showed a small forehead with tiny hairiness, arched eyebrows, thin lips, malformed ears, wide and high palate, short neck, wide thorax, bilateral hypo- plasia of the thenar and hypothenar regions; limited pronation and supination, and mus- cle hypoplasia on the external side in both feet. There was neither palpable patella nor
G U A D A L A J A R A C A M P T O D A C T Y L Y I i 55
Flg. 1. Case A (left) and Case B (right). Note nanosomy, short neck and the appearance at the knee joint in both sibs; right palpebral ptosis in Case A. The sernic- rouched stance is not due to pterygia but to hip dislo- cation.
Table 1
Quantitative Data
CASES
A B C
Age Height (cm) Weight (kg) Circumferences
Cephalic (cm) Thoracic (cm) Abdominal (cm)
Lower segment (cm) Segment ratio Arm span (cm) IQ
5y r 2y r 10mo 87* 73' 10.2" 6.5*
44' 43' 49.5* 47 44.5 48.5 37 30
83 73 75 79
1.35 1.43
5 yr 6 mo 92' 13.4'
48.7' 53 46 40
92 77
1.3
below the 3rd percentile
knee flexion. She also showed an interglu- teal pit and duck-waddle gait.
Fig. 2. Upper: Case A, close up of the hands. See camptodactyly of 2nd to 4th fingers, ulnar deviation of the 2nd and flexion contracture at the metacarpopha- langeal joint of the thumbs. Middle: Case B, close up of the hands. See mild camptodactyly mainly at the 4th and 5th fingers of the left hand, also mild ulnar deviation of the 2nd fingers and flexion contracture at the metacarpophalangeal joint of both thumbs. Lower: Close up of the feet. Case A (left), Case B (right). See overlapped, shortened 2nd toes and plano-valgus foot deformity.
Case B: The proposita's sister, aged 2 years and 10 months (Fig. l b and 2b) was the product of the 3rd full-term pregnancy and normal delivery. A striking clinical simi- larity to her affected sister was noted at birth. She underwent surgical treatment of the talipes at 2 years and 5 months of age and later of the knee limitation (with abnor-
Tab
le 2
Clin
ica
l d
ata
co
mp
are
d w
ith
oth
er
syn
dro
me
s
CA
SE
S
A B
C
G
CS
l SC
DH
PP
ENS
GS
W
FS
THS
G
OS
l SP
S N
PS
O
DD
S C
OFS
K
D
MP
S
NC
S G
OS
-ll
’& N
anos
omy
at b
irth
Sho
rt s
tatu
re
Mic
roce
phal
y P
alpe
bral
pto
sis
Mic
roph
thal
mia
O
cula
r hy
pert
elor
ism
C
lefl
pala
te
Mic
rogn
athi
a or
ret
ro-
mic
rogn
athi
a S
tiffn
ess
of te
mpo
ro-
man
dibu
lar
join
t T
ortic
ollis
B
ony
fusi
on i
n c
ervi
cal
spin
e P
ectu
s ex
cava
tum
S
colio
sis
Hip
dis
loca
tion
Hyp
opla
stic
pub
ic r
egio
n an
d ge
nita
lia
Fle
xion
con
trac
ture
s of
th
e m
etac
arpo
phal
ange
al
join
ts
Cam
ptod
acty
l y U
lnar
dev
iatio
n of
dig
its
Knu
ckle
pad
s S
ynda
ctyl
y N
ail h
ypop
lasi
a Ta
lipes
P
rom
inen
t tal
us
Ove
rlapp
ed to
es
Sho
rten
ed 2
nd to
es
Hyp
opla
stic
or
abse
nt
Mul
tiple
pte
rygi
a M
enta
l ret
arda
tion
pate
lla
++
+
+
++
+
-
+-
+
t
--
++
-
-
--
--
+
+
+-
+
+
++
++
+
+
++
-
-
--
-
-
++
+
+
++
+
+
++
+
+
--
Inhe
ritan
ce
AR A
R A
R
+* -
AD o
r AR
GC
S-I:
Gua
dala
jara
cam
ptod
acty
ly s
yndr
ome
type
I (C
antu
et
al.
1980
); SC
DH
PP:
Syn
drom
e of
cam
ptod
acty
ly, d
war
fism
, hy
pogo
nadi
sm, p
ectu
s ca
rinat
um a
nd
ptos
is (
Tem
tam
y 8 M
cKus
ick
1978
); EN
S: E
mer
y-N
elso
n sy
ndro
me
of s
hort
sta
ture
, fla
t fa
cies
and
dig
ital
cont
ract
ures
(E
mer
y 8.
Nel
son
1970
); G
S:
Gor
don
synd
rom
e (G
ordo
n et
al.
1969
); W
FS:
Whi
stlin
g-fa
ce s
yndr
ome
(Tem
tam
y 8.
McK
usic
k 19
78, C
erve
nka
et a
l. 19
70):
THS:
Tel
Has
hom
er s
yndr
ome
(Goo
dman
et a
l. 19
76);
GO
S-I:
Goo
dman
cam
ptod
acty
ly s
yndr
ome
(Goo
dman
et a
l. 19
72);
SPS:
Sm
all p
atel
la s
yndr
ome
(Sco
tt &
Tao
r 19
79);
NPS
: Nai
l-pat
ella
syn
drom
e (B
ergs
ma
1979
); O
DD
S: O
culo
dent
odig
ital s
yndr
ome
(Tho
den
et a
l. 19
77);
CO
FS:
Cer
ebro
-ocu
lo-f
acio
-ske
leta
l sy
ndro
me
(Pef
ia &
Sho
keir
1978
); K
D:
Kus
kokw
im d
isea
se
(Pet
ajan
et a
l. 19
69);
MPS
: Mul
tiple
pte
rygi
um s
yndr
ome
(Tem
tam
y 8.
McK
usic
k 19
78, S
toll
et a
l. 1980); N
CS:
New
cam
ptod
acty
ly s
yndr
ome
(Bar
aits
er 1
982)
; GO
S-
II: G
oodm
an c
ampt
odac
tyly
. syn
drom
e II
(Roz
in e
t al
. 19
84).
* B
lock
ver
tebr
ae (
T4, 5
and
6).
G U A D A L A J A R A C A M P T O D A C T Y L Y I I 57
Fig. 3. Case C at 4 years of age. Note the striking resemblance to Cases A and 8. Upper: The hands with camptodactyly of the 2nd to 5th fingers and mild flexion contracture of the metacarpophalangeal joint of the thumbs. Lower: See the planovalgus foot deformity, the overlapped and shortened 2nd toes.
ma1 findings as: atrophy of the extensor muscle group, shortened and fibrotic mus- cles with multiple bands to the surrounding structures and rudimentary patella without intercondyleal structures). Psychomotor de- velopment has been mildly delayed. The quantitative and clinical data are shown in Tables 1 and 2, respectively.
Case C: An unrelated girl of 5 years and 6 months of age (Fig. 3), was the product of the 3rd full-term pregnancy and apparently normal delivery, although perinatal data was unavailable. At birth, nanosomy and limitation of the knee movement was evi- dent. The psychomotor development has been delayed. The parents were non-con- sanguineous and the normal mother died in the post-partum period of unknown cause. The father could not be examined but was reported to be normal. The 1st product was a girl who died at 12 months of age of unknown cause and the 2nd pregnancy
ended in a spontaneous miscarriage. The quantitative and clinical data are shown in Tables 1 and 2 , respectively. Clinically, the patient showed similar features to Cases A and B; as additional signs, she presented long eyelashes, endotropia, diastasi recti, hypoplastic palmar dermal ridges, absent distal interphalangeal creases of the 2nd to the 5th fingers, bilateral Sidney’s creases, planovalgus foot deformity, shortened left pelvic limb, pilonidal dimple and several joints limited for a full extension, i.e. elbow, knee and thumbs.
The laboratory examinations in the three cases, including blood cell count, blood and urine chemistries, screening tests for meta- bolic defects (Phenistix, glucose oxidase, Millon, anthrone, ferric chloride, DNPH, nitrosonaphthol, acid albumin turbidity, CTA, methylmalonic acid, Benedic, cyanide nitroprusside), plasma and urine chromato- graphy for sugars and amino acids, serum immunoglobulins, CPK and aldolase deter-
58 C A N T U E T A L .
Fig. 4. Upper: Case A, see the severe scoliosis, wide interpedicular distance at the lumbosacral region; hypoplastic iliac and ischiopubic bones, bilateral dislocation of the hip, slenderness and bands of growth arrest on the long bones and hypoplastic displaced patella. Middle left: Camptodactyly in Case A. Middle right: Case B, see back displaced 2nd metatarsal. Lower: Also back displaced 2nd metatarsal (left Case B and center Case C). Right: Note hypoplastic patella in Case C.
G U A D A L A J A R A C A M P T O D A C T Y L Y I I 59
Table 3
Radiological findings
CASES
A B C
Microcephaly + + + Cuboid-shaped vertebral bodies + + - Wide interpedicular distance
in the lumbosacral region + + - Scoliosis + + + + Spina bifida occulta at L5 - + - Hypoplastic iliac and/or
ischiopubic bones + + + Uni or bilateral dislocation
of the hip + + + Slenderness and bands or growth
arrest on the long bones Hypoplastic, aplastic andlor
displaced patella + + f Back displaced 2nd metatarsal + + + Generalized osteopenia + + + Delayed bone age + + +
+ + +
minations, X-chromatin and karyotype (high resolution G-bands), yielded normal or negative results.
Dermatoglyphic evaluation of Case A re- vealed ATD angles of 45" (right) and 48", ulnar loops on the 3rd and 4th fingers and hypoplastic ridges in the other fingers of the right hand; an arch in the thumb, an ulnar loop in the 4th finger and hypoplastic ridges in the other fingers of the left one; absence of the distal interphalangeal creases of the 2nd to the 5th digits and equivalent simian creases in both hands. The radiological findings are shown in Table 3 (Fig. 4).
Discussion
The clinical and radiological findings in the three girls constitute a syndrome which was compared with all other syndromes with camptodactyly, intrauterine growth retar- dation and multiple malformations and hy- poplasia or agenesis of the patella. Those syndromes with a considerable resemblance to the present cases are shown in Table 2. The Multiple Pterygium Syndrome (MPS) was the closest diagnosis to be discarded,
since some of our patients' features, such as short stature, microcephaly, ptosis of the eyelids, micrognathia and scoliosis, are common to the MPS (as well as to other camptodactyly syndromes); however, the al- most complete absence of pterygia, which in MPS involves neck, axilla, antecubital, popliteal and intercrural areas, the hip dis- location, the flexion contractures of the thumbs, the short 2nd toes and the patellar defect, appear as specific stigmata of the present syndrome. Other camptodactyly syndromes (Temtamy & McKusick 1978, Bergsma 1979, Rozin et al. 1984) were also excluded on the basis of grossly different clinical features. Likewise, syndromes show- ing patellar hypoplasia or agenesis, as the von Recklinhausen syndrome (Smith 1982); and low-birthweight entities as the 3-M slen- der boned nanism (Cantu et al. 1981), Sil- ver-Russel syndrome (Escobar et al. 1978) and Dubowitz syndrome (Dubowitz 1965) were easily discarded by the absence of camptodactyly.
High resolution cytogenetic studies re- vealed normal karyotypes in our patients and thus permitted us to discard a chromo- somal origin of the malformations, spe- cifically, monosomy 2q24.2+q3 105 (Moller et al. 1984), trisomy 8 and trisomy 1Oq (de Grouchy & Turleau 1982) which include camptodactyly in their phenotypic ex- pression.
In conclusion, the intrauterine growth re- tardation-malformation syndrome in the 2 sibs reported here appears as a distinct en- tity, which, Mendelianly thinking, would correspond to an autosomal recessive pat- tern of inheritance.
To designate this syndrome, we would like to propose the term Guadalajara Camptodactyly Syndrome Type 11, since we have previously described a similar disorder as Guadalajara Camptodactyly Syndrome (Cantu et al. 1980), which actually should be named Type I.
60 C A N T U
Acknowledgments
We thank A. Barthel and A. Alcarez for thc art work, and M. E. Goiii for her secretarial assistance.
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Address: Dr. J. M . Cantk Division de Genetica Subjefatura de Inv. Cient$ca Instituto Menicano del Seqtrro Social Apartado Postal 1-3838 Guadalajara Jalisco Mexico