Radiographic findings of Desbuquois dysplasia

Abstract

Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint laxity, progressive scoliosis, and advanced carpotarsal ossification. Two different types of Desbuquois dysplasia have been identified according to the presence (Type 1) or absence (Type 2) of characteristic hand abnormalities including bifid distal thumb phalanx, an extra ossification center distal to the second metacarpal, and interphalangeal joint dislocations. Further, Kim et al have described a milder variant of Desbuquois dysplasia characterized by short stature and hands with short metacarpals, elongated proximal and distal phalanges, and extremely advanced carpal ossification. Here, we present a 19-year-old male patient with Kim variant of Desbuquois dysplasia. He displays almost all of the characteristic skeletal findings of Desbuquois dysplasia along with the characteristic hand features described by Kim et al. This patient is unique in that he also presents sagittal femoral bowing, a radiographic finding that accompanies various skeletal dysplasias but has never been reported in a patient with Desbuquois dysplasia to date.

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Cite this article as:
Özdemir M, Kavak RP. Radiographic findings of Desbuquois dysplasia. BJR Case Rep 2020; 7: 20200137.
CASE REPORT
Radiographic findings of Desbuquoisdysplasia
MELTEM ÖZDEMIR and RASIME PELIN KAVAK
Department of Radiology, University of Health Sciences Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
Address correspondence to: Dr Meltem Özdemir
E-mail: meltemkaan99@ gmail. com
CASE PRESENTATION
A 19- year- old young male with short stature admitted to
the hospital for compulsory health screening to qualify for
disability benets from the state social insurance agency.
He was a university student who complained of falling for
no reason at unexpected times. He reported that he had
been seriously injured in recent years due to these unex-
pected falls and his arm was broken in the previous year.
So, he started going to school every day under the super-
vision of his mother. He is the second child born to non-
consanguineous healthy parents of Turkish descent. His
elder sister is healthy. ere is no individual with short
stature or any kind of congenital skeletal abnormalities in
the extended family. Our patient was uneventfully born by
vaginal delivery at full term. He was born as a small baby
and has always been shorter than his peers throughout his
entire growth process. He walked late compared to his peers
and since he fell frequently, he was exempted from sports
classes throughout his education life. However, his intel-
ligence development and school success were sucient.
He nished high school at the same time as his peers. No
other signicant health problem is present in the history
of his childhood. 2 years ago, a molecular analysis of the
whole family was carried out in another university hospital.
Sanger sequencing showed a homozygous mutation in the
patient’s CANT1 gene [c.375 G < C (p. Trp125Cys)] and
the same type of heterozygous mutation in both parent’s
CANT1 genes.
He was 148 cm tall (−3.5 SD) and weighed 70 kg (body mass
index: 32, within the limits of obesity). He had dispropor-
tionately short limbs, consistent with micromelic dwarsm.
No facial dysmorphic features were noted except for mild
mid- face hypoplasia. He had bilateral genu varum, patellar
dislocation, and hyperextensibility of the knees (Figure1).
His hands appeared abnormal with exion contracture in
the distal interphalangeal joints of second to h ngers
(except in that of the third nger of the le hand) and ulnar
deviation of the h ngers. e fourth nger of the le
hand was longer than the second and the third. Both big
toes were abnormally short and both of their nails were
dysplastic. e second and third toes were elongated and
exed (Figure2).
IMAGING FINDINGS
e radiographic survey revealed generalized osteo-
penia. e dual- energy X- ray absorptiometry (DXA) scan
revealed a T- score of −3.9. On the anteroposterior (AP) full-
length radiographic view of the spine, there was S- shape
scoliosis with the upper curve convex to the right and the
lower curve convex to the le. Vertebral end- plate irreg-
ularities and narrowed disc spaces, as evidence of degen-
erative spondylosis, were present. e chest was narrow
with an increased cardiothoracic ratio (Figure3). AP pelvis
radiograph showed that the femoral necks were short and
wide. Besides, both greater trochanters were enlarged and
elevated. Lesser trochanters, as well as intertrochanteric
regions, were prominent (Figure 4). Full- length standing
Received:
10 August 2020
Accepted:
24 October 2020
Revised:
16 October 2020
https:// doi. org/ 10. 1259/ bjrcr. 20200137
ABSTRACT
Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint
laxity, progressive scoliosis, and advanced carpotarsal ossification. Two dierent types of Desbuquois dysplasia have
been identified according to the presence (Type 1) or absence (Type 2) of characteristic hand abnormalities including
bifid distal thumb phalanx, an extra ossification center distal to the second metacarpal, and interphalangeal joint dislo-
cations. Further, Kim et al have described a milder variant of Desbuquois dysplasia characterized by short stature and
hands with short metacarpals, elongated proximal and distal phalanges, and extremely advanced carpal ossification.
Here, we present a 19- year- old male patient with Kim variant of Desbuquois dysplasia. He displays almost all of the
characteristic skeletal findings of Desbuquois dysplasia along with the characteristic hand features described by Kim
et al. This patient is unique in that he also presents sagittal femoral bowing, a radiographic finding that accompanies
various skeletal dysplasias but has never been reported in a patient with Desbuquois dysplasia to date.

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Figure 1. Clinical photograph of the 19- year- old patient with
Desbuquois dysplasia.
Figure 2. Clinical photographs of the patient’s hands (a) and feet (b). There are flexion contractures in the distal interphalangeal
joints of second to fifth fingers and ulnar deviation of the fifth fingers of both hands. The fourth finger of the left hand is longer
than the second and the third (a). Both big toes are abnormally short and both of their nails are dysplastic. The second and third
toes are elongated and flexed (b).
Figure 3. Anteroposterior full- length radiographic view of the
spine. There is S- shape scoliosis with the upper curve convex
to the right and the lower curve convex to the left. There
are also vertebral end- plate irregularities and narrowed disc
spaces as evidence of degenerative spondylosis. The chest is
narrow with an increased cardiothoracic ratio.

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Case Report: Desbuquois dysplasia
AP radiograph of both lower extremities showed genu varum
deformity. Precocious osteoarthritic changes were evident in
both hip, knee and ankle joints, more prominent on the right side
(Figure 5). AP and lateral (L) knee radiographs demonstrated
bilateral anterior- bowing of the femoral shas and knee osteo-
arthritis, both of which were more pronounced on the right side.
Metaphyses of both femora and tibiae were enlarged and joint
surfaces were attened. ere was bilateral patellar dislocation
(Figure 6). Short metacarpals (more pronounced in the third
metacarpal of the le hand) and slightly elongated proximal and
middle phalanges were observed on AP and L radiographs of
both hands. Distal phalanges were short. And xed exion of the
distal interphalangeal joints of the second to h ngers of both
hands (except the third nger of the le hand) was noted. e
bilateral carpal coalition secondary to osteoarthritis was remark-
able (Figure 7). Biplanar foot and ankle radiographs demon-
strated narrow joint spaces and periarticular sclerosis in almost
all of the included joints, as the result of early osteoarthritis. e
metatarsals, as well as the phalanges, of the big toes, were short
and wide. But the phalanges of the second and third toes were
elongated. ere were plantarexion of calcanea and decreased
calcaneal inclination angles (Figure8).
In comprehensive clinical and radiological examinations, no
cardiopulmonary disorders, including cardiac septal defect and
respiratory distress, were detected. And the ophthalmologic
examination of the patient revealed no glaucoma. Based on the
rather specic molecular and radiographic ndings, the patient
was diagnosed as Kim variant of DBQD.
TREATMENT
A regular physical therapy program was planned for early- onset
osteoarthritis. e patient was educated about the course and
prognosis of the disease. Genetic counseling was provided to the
patient and other family members.
DISCUSSION
Desbuquois dysplasia (DBQD), an autosomal recessive chondro-
dysplasia characterized by severe micromelic dwarsm, joint laxity,
progressive scoliosis, and advanced carpotarsal ossication, is an
extremely rare disorder with fewer than 50 cases reported to date.
Two dierent types of DBQD have been identied depending on
whether or not the following specic hand abnormalities are present
Figure 4. Antero posterior pelvis radiograph shows short
and wide femoral necks with enlarged and elevated greater
trochanters. Lesser trochanters, as well as intertrochanteric
region, are prominent.
Figure 5. Full- length standing anteroposterior radiograph
of both lower extremities shows genu varum deformity and
precocious osteoarthritic changes in both hip, knee and ankle
joints.

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in the phenotype: bid distal thumb phalanx, an extra ossication
center distal to the second metacarpal, and dislocation of the inter-
phalangeal joints. Cases with these additional hand anomalies are
classied as Type 1, and those without them are classied as Type
2. Further, Kim et al have described a milder variant of DBQD
characterized by short stature and hands with short metacarpals,
elongated proximal and distal phalanges, and extremely advanced
carpal ossication. Both the Types 1 and 2 and the Kim variant
have been shown to result from mutations in the calcium- activated
nucleotidase 1 (CANT1) gene [DBQD-1 (MIM 251450)].1 Besides,
cases of DBQD showing mutations in the xylosyltransferase 1
(XYLT1) gene have also been reported [DBQD-2 (MIM 615777)].2
DBQD typically presents with severe pre- and post- natal growth
retardation and exhibits characteristic phenotypic and radiographic
features from the pre- natal period. However, the disease shows a
signicant heterogeneity in terms of clinical course. Furthermore,
the characteristic phenotypic and radiographic ndings evolve as
the child grows, making diagnosis more dicult in older children
and adults compared to that in young children.3,4 In the current
literature, there is a paucity of data on the radiographic appearance
of DBQD in adults. Here, we presented a young male with Kim
variant of DBQD, with emphasis on radiographic features.
According to the previously reported cases, DBQD is mostly mani-
fested by severe growth retardation and characteristic ndings that
are evident from the pre- natal period. Facial dysmorphic features
include a at face with prominent eyes and hypoplastic midface,
micrognathia, and a long upper lip with at philtrum. e distinc-
tive radiographic features of the disorder are short long bones
showing metaphyseal splay, an abnormal trochanteric structure
so- called 'Swedish key' appearance, and advanced carpal and tarsal
bone age. Various clinical features including, mental retardation,
glaucoma, lung hypoplasia, cardiac septal defects, and obesity may
accompany skeletal abnormalities.4,5 DBQD oers a signicant
heterogeneity in terms of clinical course ranging from fetal hydrops
Figure 6. Anteroposterior (a) and lateral (b) knee radiographs
demonstrate bilateral knee osteoarthritis along with anterior-
bowing of the femoral shafts, both of which were more
pronounced on the right side. Metaphyses of both femora and
tibiae are enlarged and joint surfaces are flattened. There is
bilateral patellar dislocation.
Figure 7. Antero posterior (a) and lateral (b, c) hand radio-
graphs show short metacarpals (more pronounced in the third
metacarpal of the left hand) and slightly elongated proximal
and middle phalanges. Distal phalanges are short. And fixed
flexion of the distal interphalangeal joints of the second to
fifth fingers of both hands (except the third finger of the left
hand) is evident. Bilateral carpal coalition secondary to oste-
oarthritis is remarkable.
Figure 8. Anteroposterior ankle (a), lateral right foot and
ankle (b), anteroposterior foot (c), and lateral left foot and
ankle (b) radiographs demonstrate narrow joint space and
periarticular sclerosis in almost all of the included joints, as
the result of early osteoarthritis. The phalanges and metatar-
sals of the big toes are short and wide, and the phalanges of
the second and third toes are elongated (c). There are plantar
flexion of calcanea and decreased calcaneal inclination angles
(b, d).

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Case Report: Desbuquois dysplasia
to an almost healthy life reaching to adulthood, except for various
diculties with the skeletal system.6,7 Although he showed almost
all of the characteristic skeletal ndings of DBQD, the patient we
presented was a relatively lucky one who displayed a clinical picture
that is closer to the healthy side of the clinical spectrum. He did
not have severe lung hypoplasia which has been reported to be
responsible for most deaths in early childhood among patients with
DBQD. His intelligence level was not below his peers, and he had
no facial dysmorphic features except for mild midfacial hypoplasia.
Further, while growth has been reported being extremely lagging
with standard deviation scores between −4 and −10 in most DBQD
cases, our patient’s growth retardation was relatively mild with a
standard deviation score of −3.5. On the other hand, his skeletal
ndings were rich and not mild at all.
Our patient presented with micromelic dwarsm, and ambulatory
diculties due to signicant joint laxity. Besides, he had generalized
osteopenia, scoliosis, thoracic hypoplasia, genu varum, and preco-
cious osteoarthritic changes, all of which are among the main radio-
graphic features attributed to DBQD. He had short and enlarged
femoral necks with prominent lesser trochanters. However, he did
not show the characteristic ‘Swedish key’ appearance, a distinc-
tive radiographic feature of DBQD, which is characterized by the
enlargement of the lesser trochanters with metaphyseal beaking.6
Likewise, vertebral coronal cleing, another common radiographic
nding observed in children with DBQD, was not present in our
case.8 Faivre et al pointed out that the Swedish key appearance of
the proximal femora becomes less pronounced and the vertebral
cles disappear with age.4 Supporting the observation of Faivre
et al, none of the four adult patients (between the ages of 16 and
22) presented by Kim et al showed the characteristic Swedish key
appearance or vertebral coronal cleing.9
DBQD oers remarkably distinctive hand abnormalities including
bid distal thumb phalanx, an extra ossication center distal to the
second metacarpal, and dislocation of the interphalangeal joints.
However, these highly specic hand abnormalities have been
reported to exist in only one- third of all cases.6 Further, Nizon et al
have shown that also another combination of hand abnormalities,
including multiple nger dislocations, interphalangeal epiphyseal
anomalies, and thumb digitization, without any extra ossication
center, can be observed in patients with CANT1 mutations.10 Our
patient showed none of these mentioned features. e phenotypic,
as well as radiographic features of his hands, were very similar to
those of patients reported by Kim et al.9 Both our patient and those
of Kim et al showed short metacarpals, slightly elongated proximal
and middle phalanges, short distal phalanges, almost equal length
of second to fourth ngers, xed exion of the distal interphalan-
geal joints, ulnar deviation of the h nger, and severe carpal
coalition. Besides, the phenotypic and radiographic features of our
patient’s feet were also very similar with those of Kim et al.: short
and wide metatarsals and phalanges of the great toes, and elongated
and exed second and third toes. On the other hand, the radio-
graphic features of the feet of our patient diered from those of
their patients in that he did not show metatarsus adductus or planus
valgus.9,11 e resemblance between our patient and the patients of
Kim et al was not limited only to their hands and feet. ey were
very similar to each other also in terms of normal intelligence levels,
absence of serious clinical ndings such as cardiopulmonary disor-
ders, more favorable growth retardation, and radiographic features
of the spine and proximal femora. ese close similarities strongly
suggested the diagnosis of Kim variant of DBQD in our patient.
Our patient demonstrated bilateral anterior- bowing of the femoral
shas. Sagittal bowing is, to a certain extent, a characteristic of the
human femur.12 However, the inclination in the sagittal or coronal
plane that reaches angles beyond normal anatomical boundaries is
a pathological nding that accompanies various skeletal dysplasias
such as acrofacial dysostosis, Antley- Bixler syndrome, kyphomelic
dysplasia, metaphyseal chondrodysplasia, osteogenesis imper-
fecta, spondyloepimetaphyseal dysplasia, and short- rib thoracic
dysplasia.13 To date, anterior femoral bowing has not been reported
in any DBQD cases, including those with the Kim variant. Since we
do not have access to the previous clinical records and radiological
images of the patient, we do not have information about whether
this nding is congenital or developed in the following years. But
in both cases, this additional nding appears to expand the radio-
graphic spectrum of DBQD, including that of the Kim variant. It is
clear, however, that much more case reports are needed to make an
accurate radiographic description of the disorder.
LEARNING POINTS
1. DBQD is an autosomal recessive chondrodysplasia
characterized by severe micromelic dwarfism, joint
laxity, progressive scoliosis, and advanced carpotarsal
ossification.
2. Two different types of DBQD have been identified
according to the presence (Type 1) or absence (Type 2)
of characteristic hand abnormalities including bifid distal
thumb phalanx, an extra ossification center distal to the
second metacarpal, and interphalangeal joint dislocations.
3. Kim variant of DBQD is a milder variant of the disease
that is characterized by short stature and hands with short
metacarpals, elongated proximal and distal phalanges,
and extremely advanced carpal ossification.
4. DBQD typically presents with severe pre- and post- natal
growth retardation and exhibits characteristic phenotypic
and radiographic features from the pre- natal period.
5. Anterior- bowing of the femoral shafts may be noted in
adult patients with DBQD.
CONFLICT OF INTEREST
e authors declare that they have no conict of interest.
FUNDING
is research did not receive any specic grant from funding
agencies in the public, commercial, or not- for- prot sectors.
CONSENT FOR PUBLICATION
Written informed consent was obtained from the patient for
publication of this case report, including accompanying images

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