American Journal of Medical Genetics 75:453–460 (1998)
Prenatal Growth Retardation, Pelvic Hypoplasia,
and Arthrogrypotic Changes of Lower Limbs:
A Distinct Autosomal-Recessive Disorder
Augusto Sarralde,1 Martha C. Reynoso,2 Zamira Nazará,3 Fernando Soto,4 and
Alejandro Hernández1*
1
Division de Genética, Centro de Investigación Biomédica de Occidente, Subjefactura de Investigación Cientı́fica,
Guadalajara, Mexico
2
Genética, Hospital General de Occidente, Secretaria de Salud Jalisco, Guadalajara, Jalisco, Mexico
3
Hospital de Especialidades, Departamento de Radiodiagnóstico, Centro Médico Nacional de Occidente, Instituto
Mexicano del Seguro Social, Guadalajara, Mexico
4
Facultad de Medicina, Universidad de Sinaloa, Sinaloa, Mexico
We report on 5 sibs (4 males, 1 female) with
growth retardation, severe pelvic hypopla-
sia, arthrogrypotic changes and muscular
hypotrophy of the lower limbs, and mild ver-
tebral changes of prenatal onset. To our
knowledge, this syndrome has not yet been
reported. The family history suggests auto-
somal-recessive inheritance. Am. J. Med.
Genet. 75:453–460, 1998. © 1998 Wiley-Liss, Inc.
KEY WORDS: pelvic hypoplasia; arthrogry-
potic lower limbs; muscular
hypotrophy; pelvic hypopla-
sia; short stature; autosomal-
recessive inheritance
INTRODUCTION
Arthrogryposis is a disorder characterized by con-
tractures of joints and muscles. It was reported in at
least 9 well-delineated autosomal-recessive syndromes
[McKusick, 1994]. Here we report on 4 brothers and 1
sister with an unidentified syndrome of artrogrypotic
lower limbs, muscular hypotrophy in the lower limbs,
and pelvic hypoplasia of prenatal onset, apparently
representative of autosomal-recessive inheritance.
CLINICAL REPORTS
Patient 1
The propositus (II-6 in Fig. 1) was born at term after
a normal pregnancy. A cesarean section was performed
*Correspondence to: Alejandro Hernández, M.D., División de
Genética, Centro de Investigación Biomédica de Occidente, IMSS,
AP 1-3838, Guadalajara, Jalisco, Mexico.
Received 26 December 1996; Accepted 26 August 1997
© 1998 Wiley-Liss, Inc.
because of shoulder presentation. Birth weight was 2.5
kg (5th centile), length was 47 cm (<5th centile), and
head circumference (OFC) was not recorded. At birth,
he was short and had contractures in the lower limbs.
He went through surgical treatment (arthrodesis) 3 dif-
ferent times. He walked at age 3, and his development
was otherwise normal. On physical examination at age
16 (Fig. 2), his weight was 31 kg, length 143 cm, and
U/L segment ratio 1.01 (all <5th centile). He had a wide
neck with muscular hypertrophy, winged scapulae,
lumbar scoliosis, hyperlordosis and compensatory
paravertebral muscular hypertrophy, small and nar-
row pelvis, hip contractures with 30° of limitation in
abduction, hypoplastic lower limbs with contractures of
muscles and joints, contractures of both knees at 10°,
pes planovalgus, calcaneovalgus, prominent heels, and
second and fourth toes overlapping the third and fifth,
respectively. An IQ of 85 was determined at age 17. The
main clinical data are summarized in Table I. Roent-
genological studies (Figs. 3a, 4a, 5a, and Table I)
showed normal skull and upper limbs, mildly asym-
metric thorax, cuboid and wedge-shaped vertebral bod-
ies with decreased height, lumbar scoliosis and hyper-
lordosis, normal fifth lumbar vertebra without sacral-
ization, high sacrum, short iliac wings with pelvic
hypoplasia, capital femoral hypoplasia without hip dis-
location, osteoporotic and slender long bones in lower
limbs, osteopenic feet bones, calcaneus hypoplasia,
overtubulation of first-toe metatarsal and phalanges,
radiological evidence of subluxation at metatarsopha-
langeal and interphalangeal joints, and talo-calcaneo-
tarsal coalition secondary to surgical treatment. Serum
calcium, phosphate, creatine phosphokinase, alkaline
phosphatase, lactic dehydrogenase, and glutamic-
oxalacetic transaminase were normal. Nerve conduc-
tion velocity was normal. The electromyogram (EMG)
showed normal amplitude and duration of motor unit
potential, with slightly decreased insertion activity,
findings compatible with secondary muscular atrophy.
Chromosomes were normal, 46,XY.
454 Sarralde et al.
Fig. 1. Pedigree.
Patient 2
Pregnancy and delivery were normal (II-1 in Fig. 1).
Birth weight was 2.2 kg, length was 46 cm (both <5th
centile), and OFC was not recorded. Since birth, short
stature and lower limbs contractures were evident. He
walked at age 2 with a waddling gait. At age 22 he
weighed 44 kg and was 149 cm tall (both <5th centile).
OFC was 55 cm (20th centile), and U/L segment ratio
was 1.01 (5th centile). The clinical data are summa-
rized in Table I. He had small stature, normal skull
and upper limbs, winged scapulae, moderate lumbar
scoliosis and hyperlordosis, small pelvis, hypoplastic
lower limbs with contractures of joints and muscles,
mild planovalgus, prominent heels, and flexion con-
tractures of toes with overposition of the left fourth toe
over the fifth. Serum calcium and same-serum enzyme
levels were normal. Nerve conduction velocity was nor-
mal. EMG showed reduction of motor units. This find-
ing suggested secondary muscular atrophy. With the
exception of the bilateral talus valgus, roentgenological
studies showed similar findings (Table I) to those of the
propositus, without hip dislocation or sacralization and
malformation of the fifth lumbar vertebra.
Patient 3
Patient 3 is the 12-year-old sister of the propositus
(II-8 in Fig. 1). Pregnancy was uneventful, and delivery
was at term. Birth weight was 2.25 kg (<5th centile),
length was 46 cm (5th centile), and OFC was not re-
corded. A diagnosis of arthrogryposis syndrome was
made at birth. Her growth was retarded, and she
walked at age 3. On examination (Fig. 2b), her weight
was 29.2 kg, height 128 cm (both <5th centile), OFC 52
cm (10–25th centile), and U/L segment ratio 1.12 (<5th
centile). She had striking lumbar hyperlordosis, lower-
limb hypotrophy, small and asymmetric pelvic wings,
pes planovalgus, prominent heels, calcaneus equinus,
metatarsal flexion, and second and fourth toes overlap-
ping the first and fifth, respectively. She went through
surgical arthrodesis treatment 3 different times.
Roentgenological studies (Figs. 3b, 4b, 5b, Table I)
showed cuboid and wedge vertebral bodies, lumbar hy-
perlordosis, normal fifth lumbar vertebra without sa-
cralization, high and thrown-back sacrum, pelvic hypo-
plasia with small iliac wings, severe bilateral acetabu-
lar dysplasia with congenital hip dislocation, mild
bilateral femoral head hypoplasia, positional coxa
valga, slender long bones in lower limbs, feet with gen-
eralized osteopenia, overtubulation of the first meta-
tarsal and phalanges, slender and gracile second, third,
fourth, and fifth metatarsis, metatarsophalangeal joint
subluxations with arthrosic changes, and surgical talo-
calcaneo-tarsal coalition. Results of the same labora-
tory studies were normal. Nerve conduction studies
were normal and indicated integrity of peripheral
nerves. EMG showed occasional polyphasic potentials.
Histopathology of the sural nerve and gemelli muscle
was normal.
Patient 4
Patient 4 is the 10-year-old brother (II-9 in Fig. 1) of
the propositus. Pregnancy was uneventful. He was
born after 38 weeks of normal gestation. Birth weight
was 2.0 kg, and length was 48 cm (both <5th centile).
Since birth, arthrogryposis was noted, and he was re-
ferred to the orthopedic department. He walked at age
2. On examination, weight was 23.5 kg, height was 119
cm (both <5th centile), OFC was 51.5 cm (10th centile),
and U/L segment ratio was 0.89 (25th centile). He had
a mildly asymmetric thorax, asymmetric and winged
scapulae, scoliosis and lumbar hyperlordosis, narrow
pelvis, and lower limbs with muscular atrophy and
prominent heels (Table I). Radiographic findings were
similar to those of the patients described before, with-
out evidence of lumbar vertebral malformations or hip
dislocation, and are summarized in Table I. The labo-
ratory studies were normal. Nerve conduction velocity
and EMG were normal.
Patient 5
This boy (II-10 in Fig. 1) was born at term after an
uncomplicated pregnancy and delivery. Birth weight
was 2.2 kg and length 45 cm (both <5th centile). Since
birth, congenital bilateral hip hypoplasia, and knee
and ankle contractures, were present. He walked with
support at age 4. On examination at age 8 (Fig. 2c), he
weighed 14.5 kg, was 98 cm long, and had an OFC of 49
cm (all <5th centile); U/L segment ratio was 1.08 (5th
centile). He had a forward inclination of the body,
asymmetric scapulae and thorax, cubitus valgus, small
pelvis, contractures and muscular hypotrophy in the
lower limbs, pes planovalgus, calcaneovalgus, promi-
nent heels, and contractures and overposition of the
second, third, and fourth toes (Table I). Roentgenologi-
cal studies (Figs. 3c, 4c, 5c, and Table I) show a gener-
alized osteopenia, slender long bones, cuboid and
wedge vertebral bodies with normal fifth lumbar ver-
tebra without sacralization, and pelvic hypoplasia with
small iliac wings without hip dislocation, severe osteo-
penia on the feet, overtubulation of the first-toe meta-
tarsal and phalanges, and evidence of surgical talo-
calcaneo-tarsal coalition. Laboratory studies were nor-
mal. Tibial and sural nerve conduction yielded
integrity of motor nerve conduction, and EMG showed
normal motor units. Histopatology of the left sural
nerve and left gemelli muscle showed muscular atro-
phy with increased fatty tissue, without evidence of
primary myopathy and normal nerve segment.
Family History
Clinical and radiological studies were normal in all
other relatives, including the parents. The maternal
and paternal relatives were healthy. The mother had
 Pelvic Hypoplasia and Arthrogryposis 455

Fig. 2. a: Propositus at age 16 years. Note short stature, wide neck,

small pelvis, severe hypotrophy of lower limbs with contractures, mal-
formed feet, and overlap of toes. b: Patient 3 at age 12 years. Similar
features to those of patient 1. c: Patient 5 at age 8 years. Similar clinical
picture.
456 Sarralde et al.

TABLE I. Anthropometric, Clinical, and Radiological Findings in the Patients

Anthropometric findings* Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Length (cm) 143, <5th 149, <5th 128, <5th 119, <5th 98, <5th
Weight (kg) 31.0, <5th 44.0, <5th 29.2, <5th 23.5, <5th 14.5, <5th
Head circumference (cm) 54, 10th 55, 20th 52, 10–25th 51.5, 10th 49, <5th
U/L segment ratio 1.01, <5th 1.01, 5th 1.12, <5th 0.89, 25th 1.08, 5th
Clinical findings
Short stature + + + + +
Semiflexed posture + + + + +
Muscular neck hypertrophy + + + + +
Narrow thorax + − + + +
Winged scapulas + + − + +
Paraspinal muscular hypertrophy + + + + +
Scoliosis + + + + +
Lumbar hyperlordosis + + + + +
Narrow pelvis + + + + +
Hip contractures + − + + +
Knee contractures + − + + +
Foot contractures + + + + +
Prominent hills + + + + +
Toes: short/overposition/contractures + + + + +
Muscular hypotrophy in lower limbs + + + + +
Radiological findings
Skull and upper limbs Normal Normal Normal Normal Normal
Ovoid wedge vertebral bodies,
scoliosis/lumbar hyperlordosis + + + + +
Pelvic hypoplasia + + + + +
Hip dislocation/acetabular dysplasia − − + − −
Lower limbs: skeletal hypoplasia/
osteoporotic/metatarsal fusion + + + + +
*: th 4 centile

two spontaneous abortions, and one normal son died in
early infancy because of pneumonia. The parents are
not consanguineous; however, they and the 4 grand-
parents were born in the same small village of western
Mexico (population approximately 10,000).
DISCUSSION
All 5 patients have a syndrome of prenatal growth
retardation, with notable impairment of musculo-
skeletal development of the lower limbs, manifested
mainly with contractures of joints and muscles. Other
findings include thin neck, limb girdle and spinal
muscle hypertrophy, narrow thorax, winged scapulae,
scoliosis, lumbar hyperlordosis, small pelvis, promi-
nent heels, and overposition of the toes. The predomi-
nant manifestation appears to be the severe skeletal
hypoplasia of the lower limbs, which is clearly of pre-
natal onset and may, in fact, be responsible for some of
the findings. The secondary short stature and vertebral
deformation could be due to the hypoplasia of the pelvis
and spine.
As far as we know, the combination of anomalies
reported here has not been previously described. Our
patients are different from those reported by Chitayat
et al. [1991], with a potentially lethal arthrogryposis
syndrome. Compared with them, our patients have
normal upper limbs, a muscular neck and back hyper-
trophy, and vertebral and pelvic hypoplasia, and had
neither mental retardation nor facial anomalies. Also,
our cases differ from the patients reported by Richieri-
Costa et al. [1993], with distal arthrogryposis, mental
retardation, overgrowth, cranial and facial anomalies,
thin neck, slender fingers, long hallux, joint laxity, sa-
cral dimple, and hypotonia. Chitayat et al. [1990] de-
scribed a clinical picture of distal arthrogryposis, with
facial anomalies, severe mental retardation, seizures,
cerebral malformations, and hypopituitarism. These
last findings are not present in our patients. Horslen et
al. [1994] reported a syndrome of arthrogryposis mul-
tiplex congenita, renal dysfunction, and cholestasis,
recognized as ARC syndrome. Our patients did not
show cholestatic jaundice or renal Fanconi syndrome.
Also, ours are different from the patients described by
Voupala et al. [1995], with a lethal congenital syn-
drome consisting of hypoplastic lungs and muscles, and
contractures. Pena-Shokeir syndrome is characterized
by intrauterine growth retardation, facial anomalies,
camptodactyly, contractures, pulmonar hypoplasia,
and perinatal death; other distinct subgroups of this
syndrome were identified by Ohlsson et al. [1988]. The
present cases differ from the Pena-Shokeir phenotype
because of their good prognosis, the absence of camp-
todactyly, and facial and pulmonar anomalies.
Schrander-Stumpel et al. [1991] reported on an asso-
ciation of distal arthrogryposis, developmental retar-
dation, ‘‘whistling face,’’ and Pierre Robin sequence; Il-
lum et al. [1988] described 3 similar cases with calcifi-
cations of the central nervous system. Our patients did
not show upper limb contractures or facial and nervous
system alterations. Johnston et al. [1993] described an
arthrogryposis condition of large joints with sensorial
impairment, hypoplasia of dorsal spinal roots and col-
umns, and hyperkeratosis. These neurological and der-
matological anomalies are absent in our patients.
Jaber et al. [1995] described a form of congenital ar-
throgryposis multiplex of neuropathic origin. Rose-
mann and Arad [1974] had reported a similar neuro-

genic type of a lethal congenital arthrogryposis multi-
plex. The cases we describe are different from those of
Jaber et al. [1995] and Rosemann and Arad [1974] be-
cause of the pelvis and spinal hypoplasia and the neck
and spinal muscular hypertrophy without upper limb
contractures. The phenotype of our patients resembles
Kuskokwin disease, described by Petajan et al. [1969]
Pelvic Hypoplasia and Arthrogryposis 457
Fig. 3. a: Pelvis of patient 1 with high sacrum, small iliac wings, and
pelvic and capital femoral hypoplasia. b: Pelvis of patient 3 with similar
findings, as well as acetabular dysplasia, hip dislocation, positional coxa
valga, and slender diaphysis of femora. c: Pelvis of patient 5.
in four Alaskan families with multiple joint contrac-
tures, mainly in knees and ankles, muscular atrophy,
compensatory muscle hypertrophy, spondylolisthesis,
cyst formation in the proximal portions of long bones,
and pseudoarthrosis of the clavicle and first lumbar
vertebral malformation, without mental involvement.
They had a favorable response after orthopedic treat-
458 Sarralde et al.

Fig. 4. a: Lateral view of spine of patient 1. Note lumbar hyperlordosis,

cuboid and wedge-shaped vertebral bodies with decreased height, and nor-
mal fifth lumbar vertebra without sacralization. b: Lateral view of spine of
patient 3 shows lumbar hyperlordosis, cuboid and wedge vertebral bodies,
and high and thrown-back sacrum. c: Spine of patient 5.
 Pelvic Hypoplasia and Arthrogryposis 459

Fig. 5. a: Feet of patient 1, with overtubulation of metatarsal and pha-

langes of the first toe, metatarsophalangeal and interphalangeal subluxa-
tion, and secondary talo-calcaneo-tarsal coalition. b: Feet of patient 3, with
generalized osteopenia, overtubulation of first metatarsal and phalanges,
metatarsophalangeal joint subluxations, and secondary talo-calcaneo-
tarsal coalition. c: Feet of patient 5.
460 Sarralde et al.
ment. In our patients, foot deformities required several
operations, without improvement. They did not show
upper limb contractures or cystic skeletal lesions, and
spinal and pelvic hypoplasia was present. For this rea-
son, we consider ours a different entity.
Perhaps the malformation syndrome which most
closely resembles the picture found in our patients is
that reported by Ray et al. [1986]. The skeletal resem-
blance is fairly strong, since both showed arthrogry-
potic changes in lower limbs and pelvic hypoplasia.
However, some alterations found in their patients,
such as minor facial anomalies, nasal bridge hypopla-
sia, and normal spine, are not present in our patients.
Therefore, it seems that the cases described here have
a condition of congenital anomalies unlike those previ-
ously reported, and may represent a different autoso-
mal-recessive genetic condition.
ACKNOWLEDGMENTS
The authors greatly appreciate the valuable collabo-
ration of the patients’ family. We also thank Mario
Aguilar for the artwork.
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