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The spectrum of arthrogryposis in 33 Chinese children
ELSEVIER
Brain & Development 19 (1997) 187-196
Original article
The spectrum of arthrogryposis in 33 Chinese children Virginia Wong* Division of Neurodevelopmental Paediatrics, Department of Paediatrics, The University of Hong Kong, Queen Mary. Hospital, Pokfulam Road, Hong Kong, Hong Kong
Received 12 March 1996; accepted 18 October 1996
Abstract
The clinical profile of 33 children (19 boys, 14 girls) with multiple congenital contractures has been studied. The majority (54%) belong to arthrogryposis multiplex congenita with a static clinical course. Children were classified into three groups: group I (limb involvement only; n = 21) having arthrogryposis multiplex congenita (n = 18), distal arthrogryposis syndrome (n = 2) and Streeter syndrome (n = 1); group II (limb involvement with other malformation or anomalies; n = 7) having congenital contractural arachnodactyly (n = 3), Larsen syndrome (n = 1), multiple pterygium syndrome (n = 1), craniocarpotarsal dystrophy (n = 1), and Schwartz Jampel syndrome (n = 1); and group III (limb involvement with central nervous system dysfunction or mental retardation; n = 5) having myotonia dystrophica (n = 2), congenital muscular dystrophy (n = 1), foetal alcohol syndrome (n = 1) and Pena-Shokeir syndrome (n = 1). Three children died, one each of arthrogryposis multiplex congenita, congenital contractural arachnodactyly and myotonia dystrophica. The majority had a good prognosis with independent function and mobility. © 1997 Elsevier Science B.V. Keywords: Arthrogryposis multiplex congenita; Contracture
1. Introduction
Arthrogryposis is a congenital, non-progressive limitation of movement in two or more joints in different body areas [1]. It has been used to describe patients with multiple congenital contractures. Arthrogryposis was first described by Otto (1841) who described a full term infant with multiple congenital contractures [2] as 'monstrum humanum extremitatibus incurvatius', meaning 'a human wonder with curved limbs', and referred to the condition as 'congenital myodystrophy'. Since then, multiple terms had been used to describe the clinical syndrome. Initially, the term 'multiple congenital articular rigidities' was used by Rocher (1913) [3] because the joint deformities were believed to be the primary cause of the contractures. The term 'arthrogryposis multiplex congenita' was first used by Stern (1923) to describe four children with multiple congenital contractures as having congenital limitation of movement in all joints of the extremities, with active
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and passive movement to either side being impossible [4]. Later on, other terms such as 'amyoplasia congenita', 'myodystrophia foetalis deformans', and 'congenital arthromyodysplasia' were used because the contractures were due to muscle problems, and the joints were secondarily deformed due to lack of motion and normal development [5]. Thus, although the term arthrogryposis multiplex congenita (AMC) is widely accepted, the disorder is a syndrome with more than one pathological basis. Arthrogryposis is a rare condition, with an incidence of 1 in 5 0 0 0 - 1 0 0 0 0 live births [6]. The word 'arthron' as derived from the Greek word means 'joint' whereas 'gryposis' means 'crooking or bending' [8]. The use of the term 'arthrogryposis' is different for physicians, neurologists and orthopaedic surgeons. The physician interprets arthrogryposis as deformed fusiform limbs with smooth creaseless skin and rigid joints. The neurologist tends to classify arthrogryposis into myopathic and neuropathic forms. The orthopaedic surgeon considers arthrogryposis as something special among contractures. There have been various classifications of arthrogryposis according to possible etiology, pathology, and clinical manifestations [8].
v. Wong/Brain & Development 19 (1997) 187-196
188
The therapeutic, prognostic and genetic implications vary amongst the various groups. The aim of this paper is to study the pattern of arthrogryposis in 33 Chinese children in relation to etiology, clinical manifestations, laboratory investigations and prognosis.
20 years when first seen, had multiple contractures in different body areas. The children were categorised according to Hall's classification [1]: group I (n = 15, with limb involvement only); group II (n = 7, with limb involvement and other malformation or anomalies); and group III (n = 5, with limb involvement and central nervous system dysfunction or mental retardation).
2. Subjects and methods
2.2. Clinical manifestations and laboratory investigations (Tables 2-5)
Children with contractures in more than two joints at different body areas seen prospectively and being actively followed up in the Child Assessment Centre at the Duchess of Kent Children's Hospital during the 10-year period 1985-1995 were included in this study. The inclusion criteria consist of any children with non-progressive multiple congenital contractures noted since birth. Children with contractures due to cerebral palsy, chromosomal abnormalities or spinal cord diseases are excluded. The following characteristics are analysed: site and distribution of congenital contractures, associated features, associated malformations, prenatal, perinatal and family history, and investigations in selected cases including serum CK, chromosome study, electrodiagnostic study, muscle biopsy and CAT scan of the brain.
3. Result 2.1. Distribution of cases (Table 1) Thirty-three children (19 boys, 14 girls), aged 1 day to
Table 1 Distribution of cases with arthrogryposis Group Types
Total Boys Girls
I
21 18
I1 10
10 8
2 1 7
1 0 5
1 1 2
3
3
0
1 1 1
0 0 1
1 1 0
I 5
1 3
0 2
1 2 1 1 33
1 2 0 0 19
0 0 1 1 14
III
Total
Limb involvement only Amyoplasia (arthrogryposis multiplex congenita) Distal arthrogryposis Amniotic bands (Streeter syndrome) Limb involvement+ other malformations or anomalies Congenital contractural arachnodactyly Larsen syndrome Multiple pterygium syndrome Craniocarpotarsal dystrophy (Freeman-Sheldon syndrome) Schwartz-Jampel syndrome Limb involvement + CNS dysfunction or mental retardation Fetal alcohol syndrome Myotonia dystrophica Congenital muscular dystrophy Pena Shokeir syndrome
2.2.1. Group I (limb involvement only) 2.2.1.1. Arthrogryposis multiplex congenita. Eighteen children (10 boys, 8 girls) had features of arthrogryposis multiplex congenita. They had multiple joint deformities at birth with the limbs being tubular, lacking normal skin creases, and having deep dimples at the joints. The hands and feet were small with wax-like and tapered digits. Their faces were rounded with mild micrognathia. The intelligence was normal in all. None had any positive family history of joint contractures. The pregnancy was abnormal in 12 children, with decreased or absent foetal movement (n = 3), postmaturity (n = 2), oligohydramnios (n = 2), polyhydramnios (n = 1), abnormal lie (n = 3), intrauterine growth retardation (n = 1) and prematurity with toxaemia (n = 1). Eleven children had an abnormal perinatal history, being small for date (n = 5), or with feeding problem (n = 4), foetal distress (n = 1), difficult delivery (n = 1) or fracture of the humerus (n = 1). A family history of recurrent abortion occurred in two cases. The joints mostly involved were the elbows, wrists, fingers, hips, knees and ankles. Only three children had scoliosis. The clinical course was static and all were independent in mobility with multiple orthropaedic corrections of joint deformities. One child died at the age of 3 months due to an incarcerated hernia (case 12). The serum creatine kinase level was elevated in three. Electromyography (EMG) showed myopathic features (n = 4) and neurogenic features (n = 4). Two children had normal EMG. The nerve conduction velocity was normal in six. Muscle biopsy was performed in three cases, being dystrophic pattern (n = 1). One child had mild decrease in motor conduction velocity. CAT scan of the brain was performed for four children, being normal in three and revealing mild cortical atrophy in the other.
2.2.1.2. Distal
arthrogryposis. Two children had arthrogryposis involving the hands and feet (Type I) with normal facies, stature and intelligence. The characteristic deformities of the hands included ulnar deviation of the fingers at the metacarpal-phalangeal joints, flexion contractures of the metacarpal-phalangeal
V. Wong / Brain & Development 19 (1997) 187-196
and proximal interphalangeal joints, a deeply cupped palm with a single transverse crease and a flexed and adducted thumb. Both children had a strong family history of joint deformities of the hands and feet. Distal arthrogryposis is an autosomal dominant condition with contractures of the fingers, hands and elbows giving rise to clenched hand with overlapping fingers at birth which opened to ulnar deviation, together with flex-
189
ion or extension of the elbows. The hips, knees and feet may be involved with calcaneo valgus or equinovarus posture. The toes may be involved with camptodactyly. Other associated features are trismus, short stature, cleft lip, cleft palate and scoliosis [1].
2.2.1.3. Streeter syndrome, One girl had multiple amniotic bands and joint deformities of the hands and
Table 2 Pregnancy, perinatal and family history of cases with arthrogryposis Code number
Sex
Age when seen
Pregnancy history
Perinatal history
Mode of delivery
Group I 1 2 3 4 5 6 7
M M M M M F M
20 y 3 y 8 y 8.5 y 5 y 9 y 11 y
-
Feeding problem SFD SFD SFD SFD, feeding problem
NSD NSD NSD NSD NSD LSCS NSD
8 9
M F
14y 5 y
Foetal distress
NSD LSCS
10 11 12
F F M
7y 14 y 9 m
Preterm, toxaemia, diabetes, abnormal lie of foetus Postmaturity Oligohydramnios, breech
Feeding problem Difficult delivery SFD
NSD NSD LSCS
13 14 15 16 17
F F F M F
8 1 1 1 10
18 19
M M
2.5 m 11.5 y
20
F
21 Group II 22 23 24 25 26 27
F M M M F F M
3 1 1l 12 9 3
28 Group III 29 30 31
M
15 y
M M M
D1 D1 DI
32 33
F F
d d d d m
$ Foetal movement Postmaturity $ Foetal movement, IUGR Oligohydramnios, breech -
LSCS NSD Assisted breech NSD Feeding problem
Foot presentation since 29 weeks No foetal movement all along Breech presentation, polyhydramnios Preterm
Fracture R humerus -
LSCS NSD
4 m
Oligohydramnios, IUGR
N
NSD
6y
-
N
NSD
Oligohydramnios Foetal distress
NSD NSD NSD NSD NSD
-
SFD SFD Asphyxia, feeding problem -
Exposure to alcohol, postmaturity Preterm Preterm, oligohydranmios, $ foetal movement ,1, Foetal movement -
SFD Asphyxia Asphyxia, ventilator care SFD Asphyxia
NSD NSD LSCS
m y y y y m
3 m 1m
-
Family history
m
Two previous abortions Recurrent abortion of mother (4 x )
Maternal thyrotoxicosis
LSCS
Mother, younger brother affected Father, paternal grandfather, paternal uncle, paternal cousin affected AD, mother affected -
NSD
LSCS NSD
Mother, myotonia Mother, myotonia -
F, female; M, male; d, day; m, month; y, year; AD, autosomal dominant; IUGR, intrauterine growth retardation; LSCS, lower segment caesarian section; NSD, normal spontaneous delivery; SFD, small for date.
V. Wong/ Brain & Development 19 (1997) 187-196
190
Table 3 Characteristic j o i n t i n v o l v e m e n t in children with arthrogryposis Contractures Code
Type of
number
arthrogryposis
Shoulder
Elbow
Wrist
Fingers
Hip
Knee
Ankle
Toes
Spine
1
AMC
+
+
+
+
+
+
-
-
-
2
AMC
+
-
+
+
+
-
+
-
-
3
AMC
+
-
+
+
+
+
+
-
4
AMC
+
-
+
+
+
+
+
-
5
AMC
+
+
+
+
-
-
+
-
-
6
AMC
+
-
+
+
+
+
+
-
-
+ Scoliosis
7
AMC
+
+
+
-
-
-
+
-
-
8
AMC
+
+
+
+
+
+
+
-
-
9
AMC
+
+
+
+
+
-
+
-
-
10
AMC
+
-
-
+
-
-
+
-
-
11
AMC
+
+
+
+
-
+
+
+
-
12
AMC
+
-
+
+
+
+
+
-
-
13
AMC
.
+
+
+
+
-
14
AMC
+
-
-
-
+
+
+
+
-
15
AMC
-
-
+
+
+
+
+
+
16
AMC
-
-
-
+ (L)
-
-
-
+
17
AMC
-
+ (R)
-
+
+
+
-
-
18
AMC
-
-
+
+
+
+
+
-
Scoliosis Scoliosis
.
.
.
(L)
-
19
Distal
-
-
+
+
+
+
+
+
20
Arythrogryposis
-
-
+
+
-
-
+
+
-
21
Streeter s y n d r o m e
-
-
-
+
-
-
-
+
-
Congenital contractural
-
+
+
+
+
+
-
-
G r o u p II 22
Scoliosis,
arachnodactyly 23
kyphosis
Congenital contractural
-
-
-
+
-
+
-
-
-
+
+
-
-
+
+
arachnodactyly 24
Congenital contractural
Scoliosis
arachnodactyly 25
Larsen syndrome
-
+
-
-
+
+
+
-
Scoliosis
26
Multiple pterygium
-
-
-
+
-
+
-
-
Scoliosis,
27
Freeman-Sheldon
-
-
+
+
+
+
+
28
Schwartz-Jampel
-
-
+
+
+
+
+
-
-
+
+
lordosis
syndrome (D)
syndrome +
Kyphosis
syndrome G r o u p III 29
Foetal alcohol syndrome
30
Myotonia dystrophica
-
+
-
(D)
-
31
Myotonia dystrophica
-
+
-
-
32
Congenital muscular
-
-
+
+
+
+
-
-
-
+
+ (D)
+ (D)
dystrophy 33
Pena Shokeir syndrome
+
A M C , a r t h r o g r y p o s i s m u l t i p l e x c o n g e n i t a ; D, d i s l o c a t i o n ; L, left; R, right.
feet.
She
achieved
independent
multiple
orthopaedic
amniotic
band
like
constrictions
corrections.
syndrome
functional
ability
Streeter
syndrome
is a sporadic
of the limbs
disease
with
with or ring
[1].
These
children
with
reported
features in other
described races
children limbs oval
2.2.2. Group H (limb involvement and other malformation or anomalies) cal of those
2.2.2.4. Congenital contractural arachnodactyly.
[1].
below
were
typi-
had
multiple
resembling and
seen
the
and
with
ocular Marfan
functionally died
of
Marfan
the jaws
prognathia
joint
contractures syndrome.
recessed in
Marfan
unlike
cardiovascular
syndrome. without
pneumonia
Two
Their narrow They
malformations children
orthopaedic at
the
syndrome.
and
3 months.
were
intervention. Only
one
Three
long faces skull also
thin were with
lacked
associated independent One child
child had
a
V. Wong / Brain & Development 19 (1997) 187-196
191
Table 4 Associated features in children with arthrogryposis Code number Group I 1 2 3 4
Associated features
Associated malformations
Others
Neurological
Intelligence
Clinical course
Tapering of fingers
-
-
N
Static, I
Antimongoloid slant Round face, micrognathia Tapering of fingers
-
B L inguinal hernia Dysarticulation
N N N
Static, I Static, I Static, I
-
Recurrent chest infection, squint Recurrent chest infection
Muscle atrophy areflexia Calf atrophy Calf atrophy, distal weakness -
N N
Static, I Static, I
Hypotonia, proximal muscle atrophy, areflexia, proximal and distal weakness Muscle atrophy areflexia, proximal and distal weakness Calf atrophy, distal weakness, areflexia Hypotonia, calf atrophy, distal weakness Proximal and distal weakness (UL>LL) Muscle atrophy
N
Static, 1
N
Static, I
N
Static, I
N
Static, I
N
Static, I
N
Died at 3 months
BL wasting of calf and peroneal muscles, areflexia (KJ, AJ) Wasting of muscle, areflexia -
N
Static, I
N
Static, I
N
Static, I
Hypothyroidism
-
N
Static, I
R ptosis, L convergent squint, absent patella Torticollis, low set ears, plagiocephaly, naevus flammeus BL inguinal hernia
Areflexia
N
Static, I
-
N
Static, I
-
-
N
N N N
Static, I Static, I Static, I
Marfanoid features
-
N
Died at 3 months
Marfanoid features
Proximal weakness, areflexia -
N
Static
N
Static
-
N
Static, wheelchair bound
5 6 7
Round face, micrognathia, pectus excavatum, simple ears, tapering of fingers
-
8
Macrocephaly
-
-
9
-
L K l u m p k e ' s paralysis
-
-
11
Round face, micrognathia, tapering of fingers Antimongoloid slant, tapering of fingers Round face, micrognathia
-
-
12
Round face, micrognathia
VSD
13
-
-
B L inguinal hernia, G6PD deficiency -
14
-
-
L convergent squint
15
17
Round face, micrognathia, 11 pairs trisomy hand, of ribs rocker bottom feet Facial asymmetry, plagioce- Dextrocardia phaly, bilateral simian crease Round face, micrognathia Cleft palate
18
Facial asymmetry
19 20 21
Cryptorchism . . -
10
16
Group II 22
23 24
25
Micrognathia, flat external ear External ear crumpled and flattened External ear crumpled and flattened -
VSD
.
. Absent L big toe and absent phalanges of L 4th finger Prominent occiput, high arched palate -
Microcephaly, highMarfanoid features arched palate Cleft palate, Short stature broad thumbs, big toes
V. Wong/ Brain & Development 19 (1997) 187--196
192 Table 4 continued Code number
Associatedfeatures
Associated malformations
26
Micrognathia, flat nose, low set ears, downward slanting of angle of mouth Micrognathia, neck pterygrium Hypoplastic maxilla, micrognathia, hypertelorism, clinodactyly Flat nasal bridge, hypertelorism High arched palate
27 28 Group III 29 30 31 32 33
Flat nasal bridge, high arched palate Dysmorphic facial features
Neurological
Intelligence Clinical course
Ptosis, antimon- Low posterior hair goloid slant line, short stature
-
N
Static, 1
Hypotelorism, abnormal ears -
Undescendedtestis, failureto thrive -
-
D
Static
Myotonia
N
Static
-
Undescended testis
Hypotonia,profound sensorineural deafness
D
Static
-
Hepatic failure, polycystic kidney Respiratory failure
Hypotonia, .1, jerks, weakness Hypotonia, $ jerks, proximal and distal weakness Hypotonia, proximal weakness
-
Died at 6 months
MR
Static
N
Static
-
N
Static, I
PDA
Others
Bilateral rocker bottom feet, congenital vertical talus, malrotated thumbs
AJ, anklejerk; BL, bilateral; D, delayed development;I, independent; KJ, knee jerk; LL, lower limb; N, normal; MR, mental retardation; UL, upper limb. positive family history of congenital contractural arachnodactyly with multiple contractures and Marfanoid features in the mother. Congenital contractural arachnodactyly is an autosoreal dominant condition with congenital arachnodactyly, involvement of the fingers, hands and elbows with flexion deformities of the proximal interphalangeal joints, limitation of supination and pronation. The knees may be flexed and the ankles and feet are affected with calcaneous posture; dorsiflexion and adduction of the forepart of the feet. Other associated features are kyphoscoliosis, crum-pled ear helix, club feet and congenital dislocation of the hips [1].
2.2.2.5. Larsen
syndrome. A 12-year-old girl with bilateral dislocation of hips and knees with other joint contractures had typical features of Larsen syndrome with short stature, very prominent forehead, flattened facies, depressed nasal bridge, hypertelorism, cleft palate, and fingers that were cylindrical and broad. Her clinical course was static and despite multiple orthopaedic corrections she was still wheelchair bound. 2.2.2.6. Multiple Pterygia syndrome (escobar syndrome). This 9-year-old girl had typical features of pterygia over the neck, axilla, antecubital and popliteal fossa, digital and intercrural areas. She had syndactyly of the fingers, flexion deformities of the digits, lordosis and scoliosis. She had dysmorphic facial features with flat
nose, micrognathia, low set ears, ptosis, antimongoloid slant, downward slanting of the angle of the mouth and a low posterior hair line. Her clinical course was static. This is an autosomal recessive condition characterised by multiple webs, joint contractures, camptodactyly, and other associated features like vertebral anomalies, antimongoloid slant, ptosis and cleft lip or palate. The condition is non-progressive.
2.2.2.7. Freeman-Sheldon syndrome or 'whistling face syndrome' This 3-month-old boy had bilateral dislocation of the hips and other joint contractures. He had the typical facies with a small mouth, long philtrum and micrognathia. He also had hypotelorism, abnormal ears and pterygia over the neck. This is an autosomal dominant or autosomal recessive condition characterised by an immobile face with bulging cheeks, antimongoloid eyes, microstomia, high arched palate and an ' H ' shaped tissue band chin. The fingers and hands are involved with limited movement of proximal interphalangeal joints, ulnar shift of the hands, adducted thumbs, and absence of distal interphalangeal crease. The feet may be affected with calcaneovalgus or equinovarus posture. The contractures may progress with age [ 1].
2.2.2.8. Schwartz-Jampel syndrome. This
15-year-old
V. Wong/ Brain & Development 19 (1997) 187-196
193
Table 5 Investigation in children with arthrogryposis Code number
Serum CK
Chromosome study
EMG
NCV
Muscle biopsy
Nerve biopsy
CAT scan, brain
N Myopathic Neurogenic
N N N
-
-
N -
Dystrophic pattern . .
N
Cerebral atrophy -
Group I 1
N
2 3 4
N N N
5
+
6
$
Myopathic
-
7
N
Myopathic Neurogenic Neurogenic N
N ,1. Conduc . tion velocity N N
Neurogenic . .
N .
Myopathic
8
9
N
lO
1"
N
.
N
-
-
N
-
N
N N
N Myopathic
-
N -
-
-
-
N
-
-
N Cerebral atrophy N
11 12 13 14 15 16 17
N N N N N N N
N N
18
N
N
19 20 21 Group II 22 23 24 25 26 27 28 Group III 29 30 31
-
-
N N
N N -
N Myotonia
N .
N N N
N N N
N Myotonia Myotonia
N N N
Myopathic -
-
32
N
N
Myopathic
N
Muscular dystrophy
-
33
-
-
boy
had
-
multiple
stature, kyphosis
joint
contractures,
and myotonia.
and muscle hypertrophy
relatively
short
The face was immobile
by limitation of joint movement, myopia,
myotonia,
fixed facies,
small stature and intrauterine
g r o w t h r e t a r d a t i o n ; t h e d i s e a s e is p r o g r e s s i v e . X - r a y m a y show fragmentation
.
orism,
and flattening of femoral
long
.
philtrum,
clinodactyly,
undescended
testis
and bilateral profound sensorineural deafness.
2.2.3.10. Myotonia dystrophica. T w o with
contractures
hypotonia
of the
hands
and
since birth, were diagnosed
of myotonia
boys, feet
presenting
and
marked
by demonstration
in their mothers.
epiphysis
2.2.3.11. Congenital muscular dystrophy. T h i s g i r l h a d
[1].
multiple
2.2.3. Group III (limb involvement and central nervous system dysfunction and mental retardation) 2.2.3.9. Foetal
alcohol
syndrome.
This
baby
dislocation of the left hip and other dysmorphic including
.
was obvious.
T h i s is a n a u t o s o m a l r e c e s s i v e c o n d i t i o n c h a r a c t e r i s e d blepharophimosis,
.
hypoplastic
maxilla,
micrognathia,
had
features hypertel-
Her
joint
contractures
muscle
independent
weakness
and
hypotonia
improved
since
birth.
she
was
and
with orthopaedic corrections.
2.2.3.12. Pena-Shokeir syndrome. T h i s 1 - m o n t h - o l d girl had
dislocation
contractures.
of the hips and knees
She
had
pulmonary
and other joint
hypoplasia,
bilateral
194
V. Wong / Brain & Development 19 (1997) 187-196
rocker-bottom feet, bilateral vertical talus and malro-tated thumbs, and dysmorphic facial features. This entity is an autosomal recessive lethal condition characterised by ankylosis, facial anomalies and pulmonary hypoplasia. Other associated features consist of intrauterine growth retardation, polyhydramnios, small placenta, hypertelorism and micrognathia [ 1].
3. Discussion Our spectrum of arthrogryposis in Chinese children is similar to studies in other racial groups where arthrogryposis multiplex congenita constituted the majority of cases [9-11]. The differentiation of the causes of arthrogryposis is essential as the prognosis and genetic implications vary. The various causes could be differentiated by careful prenatal and perinatal history, clinical examination and relevant investigations. In our group I and II patients, the majority had high prenatal and perinatal complications such as prematurity, postmaturity, oligohydramnios, polyhydranmios, smallfor-date, abnormal presentation and feeding problem. Most of the babies were, however, delivered vaginally. Amongst the 18 AMC children, three pregnancies were high risk ones, being recurrent abortions and maternal thyrotoxicosis. Thus, it is worthwhile performing serial prenatal ultrasound screening in high risk pregnancies to look out for arythrogryposis, and, hopefully, intervention can be undertaken earlier before irreversible contractures occur. Pedigree study revealed a positive family history only in distal arthrogryposis (autosomal dominant), congenital contractural arachnodactyly (autosomal dominant), and in myotonia dystrophica (maternally inherited). None of the family members of AMC was affected. Thus, prenatal ultrasound screening is advocated for distal arythrogryposis and congenital contractural arachnodactyly but not for AMC if index case was found in the family. Etiological analysis failed to incriminate any particular environmental toxin in our cases with arythrogryposis except for occasional cases with maternal complications of pregnancy such as toxaemia, diabetes and one case of maternal alcohol exposure. Spinal complications of arythrogryposis are more commonly seen in group II cases where five out of eight cases had scoliosis or kyphosis. Scoliosis was only found in two out of 18 children with AMC. It is essential to look out for spinal complications in arthrogryposis children in the group II category. Over 150 conditions are known with multiple congenital contractures as a predominant sign [1]. There are various classifications of arthrogryposis syndromes. The orthopaedic surgeon's classification is based on history and physical examination [7], aiming to arrive at a working diagnosis in children with various arthrogrypotic disorder~
and thus minimise the risk of choosing an inappropriate management programme. The neurologist's classification of arthrogryposis is based on pathology of whether the anterior horn cell, nerve, neuromuscular junction, muscle or the intrinsic joints and capsules are involved [ 12,13]. In 1983, Hall recommended a new classification of arthrogryposis according to a clinical approach into (i) primary limb involvement; (ii) limb involvement plus other malformations or anomalies; and (iii) limb involvement plus central nervous system dysfunction and mental retardation [14]. The genetic and etiologic basis of multiple congenital contractures is very heterogeneous. In Hall's analysis of 350 children with contractures, 28% had a recognisable genetic disorder that fitted into a single gene, chromosome or multifactorial category; 6% were due to an environmental insult or exposure to a teratogen; 46% had a known syndrome with no recurrence risk, and in 20% the diagnosis was unknown [13]. The etiology of arthrogryposis is multifactorial. There might be a congenital or acquired defect in the motor unit (anterior horn cells, roots, peripheral nerve, motor endplates or muscle), producing severe weakness early enough in foetal life to immobilise the joints at various stages in their development. The persistent immobility leads to contractures and abnormal development of the joint surfaces. Other etiological factors that can produce intrauterine limitation of motion include connective tissue disorders and mechanical blockage, e.g., structural abnormalities in the uterus due to fibroma, malformations, amniotic bands, twins and oligohydramnios [4]. Prenatal contractures in laboratory animals have been induced by viruses, neuromuscular blocking agents, toxins, insecticides, hyperthermia and limb immobilisation. In agricultural animals, these have been documented in pregnant animals feeding on plants containing toxic alkaloids or due to viral infection. Multiple etiologic factors have proven to be related to human arthrogryposis, including mutagenic agents, mitotic abnormalities, toxic chemicals or drugs, hyperthermia, neuromuscular blocking agents, and mechanical immobilisation. These factors act via the central nervous system (craniospinal motor neuraxis), motor end plates, or by primary degeneration of muscle. The resultant effect is loss of muscle power at the joints. This provokes the collagenic response which consists of partial replacement of muscle volume and collagenous thickening of the joint capsules thus leading to joint fixation [14]. The basic process in causing arthrogryposis is unknown. Pathologic processes which cause immobilisation of the limbs of the foetus may result in arthrogryposis. Various etiologic factors, including infectious agents, drugs, maternal illness and some physical insults can act directly on the motor system of the foetus, or indirectly on the environment of the foetus in causing arthrogryposis [15-27].
V. Wong / Brain & Development 19 (1997) 187-196
Pathologic studies of A M C [15], i n c l u d i n g m u s c l e biopsy and autopsy on 74 children, showed that 93% was neurogenic in origin. The c o m m o n e s t pathologic type was dysgenesis of anterior horn cells. The neurogenic type was characterised by a high incidence of other congenital anomalies while the myopathic group had few associated defects. B a n k e r [15] postulated that in both neurogenic and myopathic disorders, the contractures were due to severe weakness early in foetal d e v e l o p m e n t which i m m o b i l i s e d the joints. In a study of 21 A M C children using E M G and muscle biopsy, the lesion was neurogenic in 10 and m y o pathic in nine [28]. The major sites of contractures in our arthrogrypotic children consisted of distal upper limbs and proximal lower limb joints, whereas in S w i n y a r d ' s 70 patients, the distribution of contractures consisted of lower limb (43%), fore l i m b (46%) and upper limb (11%) and the frequency of joint i n v o l v e m e n t increased from proximal to distal limb joints in both upper and lower extremities [29]. The recurrence risk of children with arthrogryposis of u n k n o w n etiology is 4.7% if only the limbs are involved, 1.4% if the limbs plus other areas are i n v o l v e d and 7% if the central nervous system is involved. In general, the risk of unaffected parents having another affected child or of an affected person h a v i n g an affected child is 5% w h e n a specific diagnosis c a n n o t be m a d e [5]. As in other studies, the prognosis of arthrogryposis in our Chinese children is good [30]. Most of the arthrogrypotic children in group I and II categories had normal intelligence. Despite multiple congenital j o i n t contractures and deformities, the majority of children, especially the A M C group, survived with i n d e p e n d e n t functional mobility. Thus, early intervention with a multidisciplinary and interdisciplinary team m a n a g e m e n t i n v o l v i n g the orthopaedic surgeons, physiotherapists, occupational therapists, neurologists, d e v e l o p m e n t a l paediatricians, geneticists, psychologists, educators, orthotists and rehabilitation engineers is essential for p r o m o t i o n of a positive image in arythrogrypotic children. Thus, a well oriented clinical approach and laboratory investigations may help in the proper m a n a g e m e n t and genetic c o u n s e l l i n g of arthrogrypotic children with such a heterogeneous etiology.
Acknowledgements The author wishes to a c k n o w l e d g e the rehabilitation team in Duchess of Kent C h i l d r e n ' s Hospital for the dedicated care of these children.
References [1] Hall JG. Arthrogryposes (congenital contractures). In: Emery AE, Rimoin DL, editors. Principles and Practice of Medical Genetics. London: Churchill Livingstone, 1983:781-811.
195
[2] Otto AW. A human monster with inwardly curved extremities (translated from the Latin by Victor BA. From: Otto AW. Monstrum humanum extremitatibus incurvatus, Monstrorum Sexcentorum Descriptio Anatomica in Vratislaviae Museum. Anatomico-pathologeium, Breslau, 1841: 322). Clin. Orthop. 1985; 194: 4-5. [3] Rocher HL. Les radeurs articularies congenitales multiples. J. Med. Bordeaux 1913; 43: 722. [4] Stern WG. Arthrogryposis multiplex congenita. J. Am. Med. Assoc. 1923; 81: 1507-1510. [5] Thompson GH, Bilenker RM. Comprehensive management of arthrogryposis multiplex congenita. Clin. Orthop. 1985; 194: 6-14. [6] Hageman G, Willemse J. Arthrogryposis multiplex congenita. Review with comments. Neuropediatrics 1983; 14: 6-11. [7] Goldberg MJ. Arthrogryposis multiplex congenita and arthrogryposis syndromes. In: Goldberg MJ, editor. The Dysmorphic Child. An Orthopaedic Perspective. New York: Raven Press, 1987: 1-61. [8] Hageman G, Willemse J, van Ketel BA, Verdonci AFMM. The pathogenesis of fetal hypokinesia. A neurological study of 75 cases of congenital contractures with emphasis on cerebral lesions. Neuropediatrics 1987; 18: 22-33. [9] Drachman DB. The syndrome of arthrogryposis multiplex congenita. Birth Defects 1971; 7: 90-97. [10] Friedlander HL, Westin GW, Wood WL. Arthrogryposis multiplex congenita: a clinical investigation. J. Bone Joint Surg. 1968; 50: 89-112. [11] Gericke GS. Hall JC, Nelson MM, Beighton PH. Diagnostic considerations in arthrogryposis syndromes in South Africa. Clin. Genet. 1984; 25: 155-162. [12] Swaiman KF. Anterior horn cell and cranial motor neuron disease. In: Swaiman KF, editor. Pediatric Neurology: Principles and Practice. London: CV Mosby 1989; 68: 1094-1097. [13] Hall JG. Genetic aspects of arthrogryposis. Clin. Orthop. 1985: 194: 44-53. [14] Swinyard CA, Bleck EE. The etiology of arthrogryposis (multiple congenital contracture). Clin. Orthop. 1985; 194: 15-29. [15] Banker BQ. Neuropathologic aspects of arthrogryposis multiplex congenita. Clin. Orthop. 1985; 194: 30-43. [16] Banker BG, Victor M, Adams RD. Arthrogryposis multiplex due to congenital muscular dystrophy. Brain 1957; 80: 319. [17] Besser M, Beher A. Arthrogryposis accompanying congenital spinal type muscular atrophy. Arch. Dis. Child. 1967; 42: 666-670. [18] Brown LM, Robson MJ, Sharrard WJW. The pathophysiology of arthrogryposis multiplex congenita. J. Bone Joint Surg. 1980; 62: 291 296. [19] Clarren SK, Hall JG. Neuropathologic findings in the spinal cords of 10 infants with arthrogryposis. J. Neurot. Sci. 1983; 58: 89-102. [20] Dastur DK, Razzak ZA, Bharucha EP. Arthrogryposis multiplex congenita. Part II: muscle pathology and pathogenesis. J. Neurot. Neurosurg. Psychiat. 1972; 35: 435-450. [21] Drachman DB, Banker BQ. Arthrogryposis multiplex congenita. Case due to disease of the anterior horn cells. Arch. Neurol. 1961: 5: 77-93. [22] Drachman DB, Coulombre AJ. Experimental clubfoot and arthrogryposis multiplex congenita. Lancet 1962: ii: 523. [23] Ek JJ. Cerebral lesions in arthrogryposis multiplex congenita. Acta Paediatr. (Uppsala) 1958; 47:302-316. [24] Fisher RL, Johnstone WT, Westin GW, Wood WL. Arthrogryposis multiplex congenita: a clinical investigation. J. Pediatr. 1970: 76: 255-261. [25] Smit LME, Barth PG. Arthrogryposis multiplex congenita due to congenital myasthenia. Dev. Med. Child. Neurol. 1980; 22: 371374. [26] Wynne-Davies R, Lloyd-Roberts GC. Arthrogryposis multiplex congenita. Search for prenatal factors in 66 sporadic cases. Arch. Dis. Child. 1976; 51: 618-623. [27] Wynne-Davies R, Williams PF, O'Connor JCB. The 1960s epi-
196
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demic of arthrogryposis multiplex congenita. A survey from the United Kingdom, Australia, and the United States of America. J. Bone Joint Surg. 1981; 63: 76-82. [28] Strehl E, Vanasse M, Brochu P. EMG and needle muscle biopsy studies in arthrogryposis multiplex congenita. Neuropediatrics 1985; 16: 225-227.
[29] Swinyard CA, Mayer V. Multiple congenital contractures: public health considerations of arthrogryposis multiplex congenita. J. Am. Med. Assoc. 1963; 183: 23. [30] Carlson WO, Speck GJ, Vicari V, Wenger DR. Arthrogryposis multiplex congenita. A long-term follow-up study. Clin. Orthop. 1985; 194: 115-123.
Brain & Development 19 (1997) 187-196
Original article
The spectrum of arthrogryposis in 33 Chinese children Virginia Wong* Division of Neurodevelopmental Paediatrics, Department of Paediatrics, The University of Hong Kong, Queen Mary. Hospital, Pokfulam Road, Hong Kong, Hong Kong
Received 12 March 1996; accepted 18 October 1996
Abstract
The clinical profile of 33 children (19 boys, 14 girls) with multiple congenital contractures has been studied. The majority (54%) belong to arthrogryposis multiplex congenita with a static clinical course. Children were classified into three groups: group I (limb involvement only; n = 21) having arthrogryposis multiplex congenita (n = 18), distal arthrogryposis syndrome (n = 2) and Streeter syndrome (n = 1); group II (limb involvement with other malformation or anomalies; n = 7) having congenital contractural arachnodactyly (n = 3), Larsen syndrome (n = 1), multiple pterygium syndrome (n = 1), craniocarpotarsal dystrophy (n = 1), and Schwartz Jampel syndrome (n = 1); and group III (limb involvement with central nervous system dysfunction or mental retardation; n = 5) having myotonia dystrophica (n = 2), congenital muscular dystrophy (n = 1), foetal alcohol syndrome (n = 1) and Pena-Shokeir syndrome (n = 1). Three children died, one each of arthrogryposis multiplex congenita, congenital contractural arachnodactyly and myotonia dystrophica. The majority had a good prognosis with independent function and mobility. © 1997 Elsevier Science B.V. Keywords: Arthrogryposis multiplex congenita; Contracture
1. Introduction
Arthrogryposis is a congenital, non-progressive limitation of movement in two or more joints in different body areas [1]. It has been used to describe patients with multiple congenital contractures. Arthrogryposis was first described by Otto (1841) who described a full term infant with multiple congenital contractures [2] as 'monstrum humanum extremitatibus incurvatius', meaning 'a human wonder with curved limbs', and referred to the condition as 'congenital myodystrophy'. Since then, multiple terms had been used to describe the clinical syndrome. Initially, the term 'multiple congenital articular rigidities' was used by Rocher (1913) [3] because the joint deformities were believed to be the primary cause of the contractures. The term 'arthrogryposis multiplex congenita' was first used by Stern (1923) to describe four children with multiple congenital contractures as having congenital limitation of movement in all joints of the extremities, with active
* Tel.: +852-28554482; fax: +852-28551523.
0387-7604/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved PII S0387-7604(96)00557-8
and passive movement to either side being impossible [4]. Later on, other terms such as 'amyoplasia congenita', 'myodystrophia foetalis deformans', and 'congenital arthromyodysplasia' were used because the contractures were due to muscle problems, and the joints were secondarily deformed due to lack of motion and normal development [5]. Thus, although the term arthrogryposis multiplex congenita (AMC) is widely accepted, the disorder is a syndrome with more than one pathological basis. Arthrogryposis is a rare condition, with an incidence of 1 in 5 0 0 0 - 1 0 0 0 0 live births [6]. The word 'arthron' as derived from the Greek word means 'joint' whereas 'gryposis' means 'crooking or bending' [8]. The use of the term 'arthrogryposis' is different for physicians, neurologists and orthopaedic surgeons. The physician interprets arthrogryposis as deformed fusiform limbs with smooth creaseless skin and rigid joints. The neurologist tends to classify arthrogryposis into myopathic and neuropathic forms. The orthopaedic surgeon considers arthrogryposis as something special among contractures. There have been various classifications of arthrogryposis according to possible etiology, pathology, and clinical manifestations [8].
v. Wong/Brain & Development 19 (1997) 187-196
188
The therapeutic, prognostic and genetic implications vary amongst the various groups. The aim of this paper is to study the pattern of arthrogryposis in 33 Chinese children in relation to etiology, clinical manifestations, laboratory investigations and prognosis.
20 years when first seen, had multiple contractures in different body areas. The children were categorised according to Hall's classification [1]: group I (n = 15, with limb involvement only); group II (n = 7, with limb involvement and other malformation or anomalies); and group III (n = 5, with limb involvement and central nervous system dysfunction or mental retardation).
2. Subjects and methods
2.2. Clinical manifestations and laboratory investigations (Tables 2-5)
Children with contractures in more than two joints at different body areas seen prospectively and being actively followed up in the Child Assessment Centre at the Duchess of Kent Children's Hospital during the 10-year period 1985-1995 were included in this study. The inclusion criteria consist of any children with non-progressive multiple congenital contractures noted since birth. Children with contractures due to cerebral palsy, chromosomal abnormalities or spinal cord diseases are excluded. The following characteristics are analysed: site and distribution of congenital contractures, associated features, associated malformations, prenatal, perinatal and family history, and investigations in selected cases including serum CK, chromosome study, electrodiagnostic study, muscle biopsy and CAT scan of the brain.
3. Result 2.1. Distribution of cases (Table 1) Thirty-three children (19 boys, 14 girls), aged 1 day to
Table 1 Distribution of cases with arthrogryposis Group Types
Total Boys Girls
I
21 18
I1 10
10 8
2 1 7
1 0 5
1 1 2
3
3
0
1 1 1
0 0 1
1 1 0
I 5
1 3
0 2
1 2 1 1 33
1 2 0 0 19
0 0 1 1 14
III
Total
Limb involvement only Amyoplasia (arthrogryposis multiplex congenita) Distal arthrogryposis Amniotic bands (Streeter syndrome) Limb involvement+ other malformations or anomalies Congenital contractural arachnodactyly Larsen syndrome Multiple pterygium syndrome Craniocarpotarsal dystrophy (Freeman-Sheldon syndrome) Schwartz-Jampel syndrome Limb involvement + CNS dysfunction or mental retardation Fetal alcohol syndrome Myotonia dystrophica Congenital muscular dystrophy Pena Shokeir syndrome
2.2.1. Group I (limb involvement only) 2.2.1.1. Arthrogryposis multiplex congenita. Eighteen children (10 boys, 8 girls) had features of arthrogryposis multiplex congenita. They had multiple joint deformities at birth with the limbs being tubular, lacking normal skin creases, and having deep dimples at the joints. The hands and feet were small with wax-like and tapered digits. Their faces were rounded with mild micrognathia. The intelligence was normal in all. None had any positive family history of joint contractures. The pregnancy was abnormal in 12 children, with decreased or absent foetal movement (n = 3), postmaturity (n = 2), oligohydramnios (n = 2), polyhydramnios (n = 1), abnormal lie (n = 3), intrauterine growth retardation (n = 1) and prematurity with toxaemia (n = 1). Eleven children had an abnormal perinatal history, being small for date (n = 5), or with feeding problem (n = 4), foetal distress (n = 1), difficult delivery (n = 1) or fracture of the humerus (n = 1). A family history of recurrent abortion occurred in two cases. The joints mostly involved were the elbows, wrists, fingers, hips, knees and ankles. Only three children had scoliosis. The clinical course was static and all were independent in mobility with multiple orthropaedic corrections of joint deformities. One child died at the age of 3 months due to an incarcerated hernia (case 12). The serum creatine kinase level was elevated in three. Electromyography (EMG) showed myopathic features (n = 4) and neurogenic features (n = 4). Two children had normal EMG. The nerve conduction velocity was normal in six. Muscle biopsy was performed in three cases, being dystrophic pattern (n = 1). One child had mild decrease in motor conduction velocity. CAT scan of the brain was performed for four children, being normal in three and revealing mild cortical atrophy in the other.
2.2.1.2. Distal
arthrogryposis. Two children had arthrogryposis involving the hands and feet (Type I) with normal facies, stature and intelligence. The characteristic deformities of the hands included ulnar deviation of the fingers at the metacarpal-phalangeal joints, flexion contractures of the metacarpal-phalangeal
V. Wong / Brain & Development 19 (1997) 187-196
and proximal interphalangeal joints, a deeply cupped palm with a single transverse crease and a flexed and adducted thumb. Both children had a strong family history of joint deformities of the hands and feet. Distal arthrogryposis is an autosomal dominant condition with contractures of the fingers, hands and elbows giving rise to clenched hand with overlapping fingers at birth which opened to ulnar deviation, together with flex-
189
ion or extension of the elbows. The hips, knees and feet may be involved with calcaneo valgus or equinovarus posture. The toes may be involved with camptodactyly. Other associated features are trismus, short stature, cleft lip, cleft palate and scoliosis [1].
2.2.1.3. Streeter syndrome, One girl had multiple amniotic bands and joint deformities of the hands and
Table 2 Pregnancy, perinatal and family history of cases with arthrogryposis Code number
Sex
Age when seen
Pregnancy history
Perinatal history
Mode of delivery
Group I 1 2 3 4 5 6 7
M M M M M F M
20 y 3 y 8 y 8.5 y 5 y 9 y 11 y
-
Feeding problem SFD SFD SFD SFD, feeding problem
NSD NSD NSD NSD NSD LSCS NSD
8 9
M F
14y 5 y
Foetal distress
NSD LSCS
10 11 12
F F M
7y 14 y 9 m
Preterm, toxaemia, diabetes, abnormal lie of foetus Postmaturity Oligohydramnios, breech
Feeding problem Difficult delivery SFD
NSD NSD LSCS
13 14 15 16 17
F F F M F
8 1 1 1 10
18 19
M M
2.5 m 11.5 y
20
F
21 Group II 22 23 24 25 26 27
F M M M F F M
3 1 1l 12 9 3
28 Group III 29 30 31
M
15 y
M M M
D1 D1 DI
32 33
F F
d d d d m
$ Foetal movement Postmaturity $ Foetal movement, IUGR Oligohydramnios, breech -
LSCS NSD Assisted breech NSD Feeding problem
Foot presentation since 29 weeks No foetal movement all along Breech presentation, polyhydramnios Preterm
Fracture R humerus -
LSCS NSD
4 m
Oligohydramnios, IUGR
N
NSD
6y
-
N
NSD
Oligohydramnios Foetal distress
NSD NSD NSD NSD NSD
-
SFD SFD Asphyxia, feeding problem -
Exposure to alcohol, postmaturity Preterm Preterm, oligohydranmios, $ foetal movement ,1, Foetal movement -
SFD Asphyxia Asphyxia, ventilator care SFD Asphyxia
NSD NSD LSCS
m y y y y m
3 m 1m
-
Family history
m
Two previous abortions Recurrent abortion of mother (4 x )
Maternal thyrotoxicosis
LSCS
Mother, younger brother affected Father, paternal grandfather, paternal uncle, paternal cousin affected AD, mother affected -
NSD
LSCS NSD
Mother, myotonia Mother, myotonia -
F, female; M, male; d, day; m, month; y, year; AD, autosomal dominant; IUGR, intrauterine growth retardation; LSCS, lower segment caesarian section; NSD, normal spontaneous delivery; SFD, small for date.
V. Wong/ Brain & Development 19 (1997) 187-196
190
Table 3 Characteristic j o i n t i n v o l v e m e n t in children with arthrogryposis Contractures Code
Type of
number
arthrogryposis
Shoulder
Elbow
Wrist
Fingers
Hip
Knee
Ankle
Toes
Spine
1
AMC
+
+
+
+
+
+
-
-
-
2
AMC
+
-
+
+
+
-
+
-
-
3
AMC
+
-
+
+
+
+
+
-
4
AMC
+
-
+
+
+
+
+
-
5
AMC
+
+
+
+
-
-
+
-
-
6
AMC
+
-
+
+
+
+
+
-
-
+ Scoliosis
7
AMC
+
+
+
-
-
-
+
-
-
8
AMC
+
+
+
+
+
+
+
-
-
9
AMC
+
+
+
+
+
-
+
-
-
10
AMC
+
-
-
+
-
-
+
-
-
11
AMC
+
+
+
+
-
+
+
+
-
12
AMC
+
-
+
+
+
+
+
-
-
13
AMC
.
+
+
+
+
-
14
AMC
+
-
-
-
+
+
+
+
-
15
AMC
-
-
+
+
+
+
+
+
16
AMC
-
-
-
+ (L)
-
-
-
+
17
AMC
-
+ (R)
-
+
+
+
-
-
18
AMC
-
-
+
+
+
+
+
-
Scoliosis Scoliosis
.
.
.
(L)
-
19
Distal
-
-
+
+
+
+
+
+
20
Arythrogryposis
-
-
+
+
-
-
+
+
-
21
Streeter s y n d r o m e
-
-
-
+
-
-
-
+
-
Congenital contractural
-
+
+
+
+
+
-
-
G r o u p II 22
Scoliosis,
arachnodactyly 23
kyphosis
Congenital contractural
-
-
-
+
-
+
-
-
-
+
+
-
-
+
+
arachnodactyly 24
Congenital contractural
Scoliosis
arachnodactyly 25
Larsen syndrome
-
+
-
-
+
+
+
-
Scoliosis
26
Multiple pterygium
-
-
-
+
-
+
-
-
Scoliosis,
27
Freeman-Sheldon
-
-
+
+
+
+
+
28
Schwartz-Jampel
-
-
+
+
+
+
+
-
-
+
+
lordosis
syndrome (D)
syndrome +
Kyphosis
syndrome G r o u p III 29
Foetal alcohol syndrome
30
Myotonia dystrophica
-
+
-
(D)
-
31
Myotonia dystrophica
-
+
-
-
32
Congenital muscular
-
-
+
+
+
+
-
-
-
+
+ (D)
+ (D)
dystrophy 33
Pena Shokeir syndrome
+
A M C , a r t h r o g r y p o s i s m u l t i p l e x c o n g e n i t a ; D, d i s l o c a t i o n ; L, left; R, right.
feet.
She
achieved
independent
multiple
orthopaedic
amniotic
band
like
constrictions
corrections.
syndrome
functional
ability
Streeter
syndrome
is a sporadic
of the limbs
disease
with
with or ring
[1].
These
children
with
reported
features in other
described races
children limbs oval
2.2.2. Group H (limb involvement and other malformation or anomalies) cal of those
2.2.2.4. Congenital contractural arachnodactyly.
[1].
below
were
typi-
had
multiple
resembling and
seen
the
and
with
ocular Marfan
functionally died
of
Marfan
the jaws
prognathia
joint
contractures syndrome.
recessed in
Marfan
unlike
cardiovascular
syndrome. without
pneumonia
Two
Their narrow They
malformations children
orthopaedic at
the
syndrome.
and
3 months.
were
intervention. Only
one
Three
long faces skull also
thin were with
lacked
associated independent One child
child had
a
V. Wong / Brain & Development 19 (1997) 187-196
191
Table 4 Associated features in children with arthrogryposis Code number Group I 1 2 3 4
Associated features
Associated malformations
Others
Neurological
Intelligence
Clinical course
Tapering of fingers
-
-
N
Static, I
Antimongoloid slant Round face, micrognathia Tapering of fingers
-
B L inguinal hernia Dysarticulation
N N N
Static, I Static, I Static, I
-
Recurrent chest infection, squint Recurrent chest infection
Muscle atrophy areflexia Calf atrophy Calf atrophy, distal weakness -
N N
Static, I Static, I
Hypotonia, proximal muscle atrophy, areflexia, proximal and distal weakness Muscle atrophy areflexia, proximal and distal weakness Calf atrophy, distal weakness, areflexia Hypotonia, calf atrophy, distal weakness Proximal and distal weakness (UL>LL) Muscle atrophy
N
Static, 1
N
Static, I
N
Static, I
N
Static, I
N
Static, I
N
Died at 3 months
BL wasting of calf and peroneal muscles, areflexia (KJ, AJ) Wasting of muscle, areflexia -
N
Static, I
N
Static, I
N
Static, I
Hypothyroidism
-
N
Static, I
R ptosis, L convergent squint, absent patella Torticollis, low set ears, plagiocephaly, naevus flammeus BL inguinal hernia
Areflexia
N
Static, I
-
N
Static, I
-
-
N
N N N
Static, I Static, I Static, I
Marfanoid features
-
N
Died at 3 months
Marfanoid features
Proximal weakness, areflexia -
N
Static
N
Static
-
N
Static, wheelchair bound
5 6 7
Round face, micrognathia, pectus excavatum, simple ears, tapering of fingers
-
8
Macrocephaly
-
-
9
-
L K l u m p k e ' s paralysis
-
-
11
Round face, micrognathia, tapering of fingers Antimongoloid slant, tapering of fingers Round face, micrognathia
-
-
12
Round face, micrognathia
VSD
13
-
-
B L inguinal hernia, G6PD deficiency -
14
-
-
L convergent squint
15
17
Round face, micrognathia, 11 pairs trisomy hand, of ribs rocker bottom feet Facial asymmetry, plagioce- Dextrocardia phaly, bilateral simian crease Round face, micrognathia Cleft palate
18
Facial asymmetry
19 20 21
Cryptorchism . . -
10
16
Group II 22
23 24
25
Micrognathia, flat external ear External ear crumpled and flattened External ear crumpled and flattened -
VSD
.
. Absent L big toe and absent phalanges of L 4th finger Prominent occiput, high arched palate -
Microcephaly, highMarfanoid features arched palate Cleft palate, Short stature broad thumbs, big toes
V. Wong/ Brain & Development 19 (1997) 187--196
192 Table 4 continued Code number
Associatedfeatures
Associated malformations
26
Micrognathia, flat nose, low set ears, downward slanting of angle of mouth Micrognathia, neck pterygrium Hypoplastic maxilla, micrognathia, hypertelorism, clinodactyly Flat nasal bridge, hypertelorism High arched palate
27 28 Group III 29 30 31 32 33
Flat nasal bridge, high arched palate Dysmorphic facial features
Neurological
Intelligence Clinical course
Ptosis, antimon- Low posterior hair goloid slant line, short stature
-
N
Static, 1
Hypotelorism, abnormal ears -
Undescendedtestis, failureto thrive -
-
D
Static
Myotonia
N
Static
-
Undescended testis
Hypotonia,profound sensorineural deafness
D
Static
-
Hepatic failure, polycystic kidney Respiratory failure
Hypotonia, .1, jerks, weakness Hypotonia, $ jerks, proximal and distal weakness Hypotonia, proximal weakness
-
Died at 6 months
MR
Static
N
Static
-
N
Static, I
PDA
Others
Bilateral rocker bottom feet, congenital vertical talus, malrotated thumbs
AJ, anklejerk; BL, bilateral; D, delayed development;I, independent; KJ, knee jerk; LL, lower limb; N, normal; MR, mental retardation; UL, upper limb. positive family history of congenital contractural arachnodactyly with multiple contractures and Marfanoid features in the mother. Congenital contractural arachnodactyly is an autosoreal dominant condition with congenital arachnodactyly, involvement of the fingers, hands and elbows with flexion deformities of the proximal interphalangeal joints, limitation of supination and pronation. The knees may be flexed and the ankles and feet are affected with calcaneous posture; dorsiflexion and adduction of the forepart of the feet. Other associated features are kyphoscoliosis, crum-pled ear helix, club feet and congenital dislocation of the hips [1].
2.2.2.5. Larsen
syndrome. A 12-year-old girl with bilateral dislocation of hips and knees with other joint contractures had typical features of Larsen syndrome with short stature, very prominent forehead, flattened facies, depressed nasal bridge, hypertelorism, cleft palate, and fingers that were cylindrical and broad. Her clinical course was static and despite multiple orthopaedic corrections she was still wheelchair bound. 2.2.2.6. Multiple Pterygia syndrome (escobar syndrome). This 9-year-old girl had typical features of pterygia over the neck, axilla, antecubital and popliteal fossa, digital and intercrural areas. She had syndactyly of the fingers, flexion deformities of the digits, lordosis and scoliosis. She had dysmorphic facial features with flat
nose, micrognathia, low set ears, ptosis, antimongoloid slant, downward slanting of the angle of the mouth and a low posterior hair line. Her clinical course was static. This is an autosomal recessive condition characterised by multiple webs, joint contractures, camptodactyly, and other associated features like vertebral anomalies, antimongoloid slant, ptosis and cleft lip or palate. The condition is non-progressive.
2.2.2.7. Freeman-Sheldon syndrome or 'whistling face syndrome' This 3-month-old boy had bilateral dislocation of the hips and other joint contractures. He had the typical facies with a small mouth, long philtrum and micrognathia. He also had hypotelorism, abnormal ears and pterygia over the neck. This is an autosomal dominant or autosomal recessive condition characterised by an immobile face with bulging cheeks, antimongoloid eyes, microstomia, high arched palate and an ' H ' shaped tissue band chin. The fingers and hands are involved with limited movement of proximal interphalangeal joints, ulnar shift of the hands, adducted thumbs, and absence of distal interphalangeal crease. The feet may be affected with calcaneovalgus or equinovarus posture. The contractures may progress with age [ 1].
2.2.2.8. Schwartz-Jampel syndrome. This
15-year-old
V. Wong/ Brain & Development 19 (1997) 187-196
193
Table 5 Investigation in children with arthrogryposis Code number
Serum CK
Chromosome study
EMG
NCV
Muscle biopsy
Nerve biopsy
CAT scan, brain
N Myopathic Neurogenic
N N N
-
-
N -
Dystrophic pattern . .
N
Cerebral atrophy -
Group I 1
N
2 3 4
N N N
5
+
6
$
Myopathic
-
7
N
Myopathic Neurogenic Neurogenic N
N ,1. Conduc . tion velocity N N
Neurogenic . .
N .
Myopathic
8
9
N
lO
1"
N
.
N
-
-
N
-
N
N N
N Myopathic
-
N -
-
-
-
N
-
-
N Cerebral atrophy N
11 12 13 14 15 16 17
N N N N N N N
N N
18
N
N
19 20 21 Group II 22 23 24 25 26 27 28 Group III 29 30 31
-
-
N N
N N -
N Myotonia
N .
N N N
N N N
N Myotonia Myotonia
N N N
Myopathic -
-
32
N
N
Myopathic
N
Muscular dystrophy
-
33
-
-
boy
had
-
multiple
stature, kyphosis
joint
contractures,
and myotonia.
and muscle hypertrophy
relatively
short
The face was immobile
by limitation of joint movement, myopia,
myotonia,
fixed facies,
small stature and intrauterine
g r o w t h r e t a r d a t i o n ; t h e d i s e a s e is p r o g r e s s i v e . X - r a y m a y show fragmentation
.
orism,
and flattening of femoral
long
.
philtrum,
clinodactyly,
undescended
testis
and bilateral profound sensorineural deafness.
2.2.3.10. Myotonia dystrophica. T w o with
contractures
hypotonia
of the
hands
and
since birth, were diagnosed
of myotonia
boys, feet
presenting
and
marked
by demonstration
in their mothers.
epiphysis
2.2.3.11. Congenital muscular dystrophy. T h i s g i r l h a d
[1].
multiple
2.2.3. Group III (limb involvement and central nervous system dysfunction and mental retardation) 2.2.3.9. Foetal
alcohol
syndrome.
This
baby
dislocation of the left hip and other dysmorphic including
.
was obvious.
T h i s is a n a u t o s o m a l r e c e s s i v e c o n d i t i o n c h a r a c t e r i s e d blepharophimosis,
.
hypoplastic
maxilla,
micrognathia,
had
features hypertel-
Her
joint
contractures
muscle
independent
weakness
and
hypotonia
improved
since
birth.
she
was
and
with orthopaedic corrections.
2.2.3.12. Pena-Shokeir syndrome. T h i s 1 - m o n t h - o l d girl had
dislocation
contractures.
of the hips and knees
She
had
pulmonary
and other joint
hypoplasia,
bilateral
194
V. Wong / Brain & Development 19 (1997) 187-196
rocker-bottom feet, bilateral vertical talus and malro-tated thumbs, and dysmorphic facial features. This entity is an autosomal recessive lethal condition characterised by ankylosis, facial anomalies and pulmonary hypoplasia. Other associated features consist of intrauterine growth retardation, polyhydramnios, small placenta, hypertelorism and micrognathia [ 1].
3. Discussion Our spectrum of arthrogryposis in Chinese children is similar to studies in other racial groups where arthrogryposis multiplex congenita constituted the majority of cases [9-11]. The differentiation of the causes of arthrogryposis is essential as the prognosis and genetic implications vary. The various causes could be differentiated by careful prenatal and perinatal history, clinical examination and relevant investigations. In our group I and II patients, the majority had high prenatal and perinatal complications such as prematurity, postmaturity, oligohydramnios, polyhydranmios, smallfor-date, abnormal presentation and feeding problem. Most of the babies were, however, delivered vaginally. Amongst the 18 AMC children, three pregnancies were high risk ones, being recurrent abortions and maternal thyrotoxicosis. Thus, it is worthwhile performing serial prenatal ultrasound screening in high risk pregnancies to look out for arythrogryposis, and, hopefully, intervention can be undertaken earlier before irreversible contractures occur. Pedigree study revealed a positive family history only in distal arthrogryposis (autosomal dominant), congenital contractural arachnodactyly (autosomal dominant), and in myotonia dystrophica (maternally inherited). None of the family members of AMC was affected. Thus, prenatal ultrasound screening is advocated for distal arythrogryposis and congenital contractural arachnodactyly but not for AMC if index case was found in the family. Etiological analysis failed to incriminate any particular environmental toxin in our cases with arythrogryposis except for occasional cases with maternal complications of pregnancy such as toxaemia, diabetes and one case of maternal alcohol exposure. Spinal complications of arythrogryposis are more commonly seen in group II cases where five out of eight cases had scoliosis or kyphosis. Scoliosis was only found in two out of 18 children with AMC. It is essential to look out for spinal complications in arthrogryposis children in the group II category. Over 150 conditions are known with multiple congenital contractures as a predominant sign [1]. There are various classifications of arthrogryposis syndromes. The orthopaedic surgeon's classification is based on history and physical examination [7], aiming to arrive at a working diagnosis in children with various arthrogrypotic disorder~
and thus minimise the risk of choosing an inappropriate management programme. The neurologist's classification of arthrogryposis is based on pathology of whether the anterior horn cell, nerve, neuromuscular junction, muscle or the intrinsic joints and capsules are involved [ 12,13]. In 1983, Hall recommended a new classification of arthrogryposis according to a clinical approach into (i) primary limb involvement; (ii) limb involvement plus other malformations or anomalies; and (iii) limb involvement plus central nervous system dysfunction and mental retardation [14]. The genetic and etiologic basis of multiple congenital contractures is very heterogeneous. In Hall's analysis of 350 children with contractures, 28% had a recognisable genetic disorder that fitted into a single gene, chromosome or multifactorial category; 6% were due to an environmental insult or exposure to a teratogen; 46% had a known syndrome with no recurrence risk, and in 20% the diagnosis was unknown [13]. The etiology of arthrogryposis is multifactorial. There might be a congenital or acquired defect in the motor unit (anterior horn cells, roots, peripheral nerve, motor endplates or muscle), producing severe weakness early enough in foetal life to immobilise the joints at various stages in their development. The persistent immobility leads to contractures and abnormal development of the joint surfaces. Other etiological factors that can produce intrauterine limitation of motion include connective tissue disorders and mechanical blockage, e.g., structural abnormalities in the uterus due to fibroma, malformations, amniotic bands, twins and oligohydramnios [4]. Prenatal contractures in laboratory animals have been induced by viruses, neuromuscular blocking agents, toxins, insecticides, hyperthermia and limb immobilisation. In agricultural animals, these have been documented in pregnant animals feeding on plants containing toxic alkaloids or due to viral infection. Multiple etiologic factors have proven to be related to human arthrogryposis, including mutagenic agents, mitotic abnormalities, toxic chemicals or drugs, hyperthermia, neuromuscular blocking agents, and mechanical immobilisation. These factors act via the central nervous system (craniospinal motor neuraxis), motor end plates, or by primary degeneration of muscle. The resultant effect is loss of muscle power at the joints. This provokes the collagenic response which consists of partial replacement of muscle volume and collagenous thickening of the joint capsules thus leading to joint fixation [14]. The basic process in causing arthrogryposis is unknown. Pathologic processes which cause immobilisation of the limbs of the foetus may result in arthrogryposis. Various etiologic factors, including infectious agents, drugs, maternal illness and some physical insults can act directly on the motor system of the foetus, or indirectly on the environment of the foetus in causing arthrogryposis [15-27].
V. Wong / Brain & Development 19 (1997) 187-196
Pathologic studies of A M C [15], i n c l u d i n g m u s c l e biopsy and autopsy on 74 children, showed that 93% was neurogenic in origin. The c o m m o n e s t pathologic type was dysgenesis of anterior horn cells. The neurogenic type was characterised by a high incidence of other congenital anomalies while the myopathic group had few associated defects. B a n k e r [15] postulated that in both neurogenic and myopathic disorders, the contractures were due to severe weakness early in foetal d e v e l o p m e n t which i m m o b i l i s e d the joints. In a study of 21 A M C children using E M G and muscle biopsy, the lesion was neurogenic in 10 and m y o pathic in nine [28]. The major sites of contractures in our arthrogrypotic children consisted of distal upper limbs and proximal lower limb joints, whereas in S w i n y a r d ' s 70 patients, the distribution of contractures consisted of lower limb (43%), fore l i m b (46%) and upper limb (11%) and the frequency of joint i n v o l v e m e n t increased from proximal to distal limb joints in both upper and lower extremities [29]. The recurrence risk of children with arthrogryposis of u n k n o w n etiology is 4.7% if only the limbs are involved, 1.4% if the limbs plus other areas are i n v o l v e d and 7% if the central nervous system is involved. In general, the risk of unaffected parents having another affected child or of an affected person h a v i n g an affected child is 5% w h e n a specific diagnosis c a n n o t be m a d e [5]. As in other studies, the prognosis of arthrogryposis in our Chinese children is good [30]. Most of the arthrogrypotic children in group I and II categories had normal intelligence. Despite multiple congenital j o i n t contractures and deformities, the majority of children, especially the A M C group, survived with i n d e p e n d e n t functional mobility. Thus, early intervention with a multidisciplinary and interdisciplinary team m a n a g e m e n t i n v o l v i n g the orthopaedic surgeons, physiotherapists, occupational therapists, neurologists, d e v e l o p m e n t a l paediatricians, geneticists, psychologists, educators, orthotists and rehabilitation engineers is essential for p r o m o t i o n of a positive image in arythrogrypotic children. Thus, a well oriented clinical approach and laboratory investigations may help in the proper m a n a g e m e n t and genetic c o u n s e l l i n g of arthrogrypotic children with such a heterogeneous etiology.
Acknowledgements The author wishes to a c k n o w l e d g e the rehabilitation team in Duchess of Kent C h i l d r e n ' s Hospital for the dedicated care of these children.
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