Pseudoachondroplasia: Report on a South African family
S Moosa,1
MB BCh, DCH (SA); G Nishimura,2
MD
1
Division of Human Genetics,
National Health Laboratory Service and School of Pathology,
University of the Witwatersrand, Johannesburg, South Africa
2
Department of Pediatric Imaging, Tokyo
Metropolitan Children’s Medical Center, Tokyo, Japan
Pseudoachondroplasia is an autosomal dominant skeletal
dysplasia that results in disproportionately short stature,
severe brachydactyly with strikingly lax small joints,
malalignments of the lower limbs, and characteristic
radiological features. Although named ‘false achondroplasia’,
the entity is a distinct condition, in which affected
individuals are born with normal length and have a normal
facies, but is often only recognised after the age of 2 years,
when the disproportion and waddling gait become evident. We
report on an affected South African father and daughter, and
highlight their clinical and radiographic features.
S Afr J Rad 2013;17(2):65-67.
DOI:10.7196/SAJR.767
Pseudoachondroplasia (OMIM 177170) is an autosomal dominant
skeletal dysplasia that results in disproportionately
(micromelic) short stature, severe brachydactyly with strikingly
lax small joints, various malalignments of the lower limbs owing
to laxity of the large joints, and characteristic radiological
features. Although named ‘false achondroplasia’, the entity is a
distinct condition in which affected individuals are born with
normal length and have a normal facies. It is often only
recognised after the age of 2 years, when the disproportion and
waddling gait become evident. The radiological manifestations
are descriptively termed spondylo-epi-metaphyseal dysplasia
(SEMD). Significant retardation of epiphyseal ossification
manifests with small, round epiphyses. The epiphyseal dysplasia
leads to premature degenerative joint disease. The metaphyses
are irregularly ossified. The vertebral bodies appear mildly
flat with biconvex endplates. The distinctive vertebral
anomalies, apparent in pre-pubertal individuals, often resolve
with age, thus emphasising the importance of correct diagnosis
in childhood. We present a South African (SA) family with an
affected father and daughter, and highlight their clinical and
radiographic features.
Clinical features
The proband was a 12-year-old girl who presented with short
stature and painful knees and ankles (Fig. 1). She was reported
to have normal birth length and was of average intelligence. Her
height was 104.5 cm (<<3rd centile), and her
upper-to-lower segment ratio 1.6 (increased) and arm span was
92.5 cm (decreased). Weight and head circumference were normal.
She stood with an exaggerated lumbar lordosis and had a waddling
gait. She had no facial dysmorphic features. The upper limbs
showed shortening of all segments with prominent joints of the
elbow and wrists. The elbow joints were restricted, while the
wrist and finger joints showed hyperlaxity. Brachydactyly with
squared fingertips and deepset nails was found. The lower limbs
showed marked genu varus, shortening of all limb segments and
flat, short feet. Mild lumbar scoliosis was evident.
Her 48-year-old father was found to have a very similar
phenotype (Fig. 2). He presented with difficulty in walking and
with painful knee and hip joints. Genu valgus (L>R) was
noted, and all joints were stiff. His face, upper limbs and feet
resembled those of his daughter. His height was 125.5 cm
(<<3rd centile), with a decreased arm span and increased
upper-to-lower segment ratio.
Radiographic features
Radiographs of these two affected individuals showed skeletal
changes involving the spine, metaphyses and epiphyses of tubular
bones descriptively termed SEMD (Figs 3 - 7). The proband
exhibited biconvex deformity with anterior beaking of the
vertebral bodies, but platyspondyly was not evident. Mild
thoracolumbar gibbus was noted, with hypoplasia of the first
vertebral body (Fig. 3). The ilia were somewhat hypoplastic
along with mildly short greater sciatic notches and steep,
irregular acetabulae. The proximal femoral epiphyses were small
and round. Ossification of the greater trochanters was irregular
(Fig. 6). The epiphyses of other long bones were also small and
irregular in ossification. The metaphyses of the long bones were
flared and irregular. Spur-like projections were noted in some
of the metaphyseal margins, particularly of the proximal tibiae
(Figs 5 and 6). Carpal bones showed delayed ossification and
irregular margins. The short tubular bones showed significant
shortening along with epiphyseal irregularities (Fig. 7). Spinal
radiographs of the father demonstrated thoracolumbar scoliosis
with mild modification of the vertebral bodies (Fig. 4).
Discussion
Pseudoachondroplasia was first described by Maroteaux and
Lamy in 1959.1 As the most common of
the SEMD group of disorders, it is estimated to affect 1 in
every 20 000 individuals.2 Typically, affected individuals
have a normal birth length and no facial dysmorphic features.
Joint laxity, particularly of the small joints of the hand, is
another clinical hallmark. As in this family, joint pain is a
common presenting symptom. The lower limbs may show genu
valgus, varus or a windswept deformity.
The characteristic radiographic features include: (i)
delayed epiphyseal ossification and irregular metaphyses of
the long bones with small capital femoral epiphyses, short
femoral necks and irregular, flared metaphyseal borders, and
small pelvis and poorly modelled acetabulae with irregular
margins that may be sclerotic, especially in older
individuals; (ii) significant brachydactyly,
particularly short metacarpals and phalanges with irregular
metaphyses and small, irregular carpal bones; and (iii)
anterior beaking or tonguing of the vertebral bodies, biconvex
vertebral endplates, and platyspondyly in childhood. This
distinctive appearance of the vertebrae normalises with age,
emphasising the importance of obtaining the necessary images
in childhood, to aid in making a definitive diagnosis.
The proband was 12 years old at the time that the accompanying radiographs were taken, and the platyspondyly had already resolved. Unfortunately, no earlier spinal images were available. The natural history of pseudoachondroplasia includes osteoarthritic changes of the extremities and the spine, which are related to abnormal epiphyseal development, along with joint laxity, and may occur in early adult life. Spinal osteoarthropathy may be associated with scoliosis. Degenerative joint disease is progressive; approximately half of all affected individuals eventually require hip replacement surgery.3
Pseudoachondroplasia is inherited in an autosomal dominant manner. Therefore, an affected individual has a 50% chance at every pregnancy of passing the condition on to the next generation. Mutations in the COMP gene, which encodes the cartilage oligomeric matrix protein, cause pseudoachondroplasia. This protein is a normal constituent of the extracellular matrix in cartilage, ligaments and tendons. When the gene is mutated, an abnormal accumulation of proteoglycans within cartilage cells occurs, which leads to early death of these cells and ultimately to defective bone growth and modelling.2
As molecular genetic testing is not yet available in SA, the
diagnosis remains clinico-radiological. Ongoing care of affected
individuals requires the participation of a multidisciplinary
team to address their joint pain, limb deformities, scoliosis
and psychosocial issues related to short stature. Timeous
referral for evaluation by a medical geneticist is invaluable in
confirming the diagnosis, providing genetic counselling to
affected families and directing future management.
1. Maroteaux, P, Lamy M. Les formes pseudo-achondroplastiques des dysplasies spondylo-epiphysaires. Presse Med 1959;67:383-386.
2. Tufan AC, Satiroglu-Tufan NL, Jackson GC, Semerci CN, Solak S, Yagci B. Serum or plasma cartilage oligomeric matrix protein concentration as a diagnostic marker in pseudoachondroplasia: Differential diagnosis of a family. Eur J Hum Genet 2007;15:1023-1028.
3. Online Mendelian Inheritance in Man. MIM Number: 177170. Baltimore, USA: Johns Hopkins University, 13 April 2010. http://omim.org (accessed 16 June 2012).