Editor-in-Chief:
Journal of Clinical Imaging Science
Vikram S. Dogra, MD
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Department of Imaging Sciences, University of
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Rochester Medical Center, Rochester, USA
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CASE REPORT
Report of Two Siblings with Overlapping
Features of Ellis-van Creveld and Weyers
Acrodental Dysostosis
Devi C. Shetty, Harkanwal P. Singh, Prince Kumar1, Chanchal Verma
Departments of Oral and Maxillofacial Pathology and Microbiology, 1Prosthodontics and Oral Implantology,
I.T.S. Center for Dental Studies and Research, Muradnagar, Ghaziabad, Uttar Pradesh, India
Address for correspondence:
Dr. Harkanwal Preet Singh,
Department of Oral and Maxillofacial
Pathology and Microbiology,
I.T.S. Center for Dental Studies and
Research, Muradnagar, Ghaziabad –
201 206, Uttar Pradesh, India.
E-mail: hkps0320@gmail.com
ABSTRACT
Skeletal dysplasias are a heterogenous group of disorders combining abnormalities
in the skull and other skeletal bones. Weyers acrofacial dysostosis also known as
Weyers acrodental dysostosis was first described in 1952, by Weyers, as a postaxial
polydactyly, which had features distinct from, yet some in common with the Ellisvan Creveld Syndrome (EvC). Both the syndromes have been mapped to the same
chromosome, 4p16. The cases reported here highlight the overlapping features
of both syndromes, which are dissimilar in mode of inheritance and phenotypic
severity, emphasizing the need for genetic analysis, to categorize these conditions.
Received : 23-02-2012
Accepted : 31-03-2012
Key words: Ellis-van Creveld, polydactyly, syndrome, weyers acrodental dysostosis
Published : 28-04-2012
INTRODUCTION
A syndrome is a group of signs and symptoms that
occur together and characterize a particular disease or
abnormality. The abnormalities or defects can involve
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DOI:
10.4103/2156-7514.95432
multiple systems. It is characteristic of certain of these
conditions to follow a strict Mendelian pattern of
heredity. An adequate in-depth investigative record of
the individual who is presenting with such condition is
essential.
Skeletal dysplasias are a heterogenous group of disorders
that result in a disproportionate short stature. Attempting
to reach a unified nomenclature system, an International
Nomenclature and Classification was proposed in 1969,
which was subsequently updated in the years 1992 and
1997. In the 2001 revision, the term ‘dysostoses’ was
incorporated, which referred to malformations of individual
Copyright: © 2012 Shetty DC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original author and source are credited.
This article may be cited as:
Shetty DC, Singh HP, Kumar P, Verma C. Report of Two Siblings with Overlapping Features of Ellis-van Creveld and Weyers Acrodental Dysostosis. J Clin Imaging Sci 2012;2:18.
Available FREE in open access from: http://www.clinicalimagingscience.org/text.asp?2012/2/1/18/95432
Journal of Clinical Imaging Science | Vol. 2 | Issue 1 | Apr-June 2012
1
Shetty, et al.: Weyer’s acrofacial dysostoses
bones, single or in combination, and did not refer to a
generalized disorder of the skeleton.[1]
down teeth, desiring treatment and replacement of the
missing teeth.
The acrofacial dysostoses are a heterogenous group of
disorders that affect the skull and other skeletal bones.
The Curry Hall syndrome (Weyer’s acrofacial dysostosis)
was first described in 1952, by Weyer, as postaxial
polydactyly (POADS), now also known as the Miller’s
syndrome. He proposed the name acrofacial dysostoses
and suggested an autosomal mode of inheritance. The
syndrome is characterized by postaxial polydactyly,
dysplastic nails, oligodontia, enamel hypoplasia, and
conical teeth.[2]
Case 1
Weyer’s acrofacial dysostosis is distinct from, and yet
has some features in common with, the Elli-van Creveld
syndrome (EvC, MIM 225500). EvC is an autosomal recessive
skeletal dysplasia characterized by short limbs, short ribs,
postaxial polydactyly, and dysplastic nails and teeth.
Congenital cardiac defects, most commonly defects of
primary atrial septation producing a common atrium,
occur in 60% of the affected individuals. This entity has
been mapped to chromosome 4p16, which is same as
that affected in Weyer’s Acrofacial Dysostoses.[3,4] Majority
of EvC patients have mutations either in EVC or EVC2 and
the phenotypes associated with mutations in these genes
are clinically indistinguishable, whereas, in the Weyers
syndrome only two mutations, S307P in EVC and c.3793delC
in EVC2, have been identified to date. There are very few
Weyers cases described with mutations and interestingly
most of them have been found carrying heterozygous
mutations in the last exon of EVC2. [5] Weyer syndrome
has a lower prevalence than EvC and is considered a less
severe form.[5,6]
We present two cases of a 15-year-old boy and his 14-year-old
sister, presenting with features suggesting partial expression
of Weyer’s acrofacial dysostoses and an overlap with the
features of the EvC syndrome. Through these case reports
we would be highlighting the need for a methodology for
classifying or naming the syndromes where a heterogenous
group of disorders are present. This would be pertinent and
have a specific relevance to a situation where syndromes
show an overlap of the features of differing designations, and
would also address the problem of identifying the syndrome
in cases of partial expression of the phenotypes.
The 15-year-old boy was apparently asymptomatic up till
seven years of age when he had first noticed the beginning
of discoloration and chipping of his teeth. Subsequently
many teeth were found to be carious and he had undergone
multiple extractions over the past 8 years.
On general examination, a short stature (138 cm), with
short limbs and a moderate build were noted. Frontal
bossing with receding hairline [Figure 1], hypotelorism with
antimongoloid slant of the eyes was also seen [Figure 1].
Facial asymmetry with a depressed midface and protruding
mandible were evident.
A thorough intra-oral examination revealed oligodontia,
with widely spaced, discolored, malformed dentition, and
over-retained deciduous teeth with pulpal exposure in all
teeth [Figure 2]. Partial ankyloglossia was also seen [Figure 3].
A detailed radiographic analysis with complete skeletal
Figure 1: Extra-oral photograph shows protruding mandible and hypotelorism.
CASE REPORTS
A 15-year-old-boy and his 14-year -old sister, the third
and fourth among eight children of consanguineous
andnormally developed parents reported to the department
with a major common complaint of discolored and worn
2
Figure 2: Intra-oral photograph shows malformed dentition with pulpal exposure
of all teeth in the maxillary arch.
Journal of Clinical Imaging Science | Vol. 2 | Issue 1 | Apr-June 2012
Shetty, et al.: Weyer’s acrofacial dysostoses
radiographs was performed. An Orthopantomogram (OPG)
revealed multiple unerupted permanent teeth, multiple
missing permanent tooth germs, short roots, and enlarged
pulpal chambers [Figure 4].
Cephalometric analysis of the lateral cephalogram
confirmed the presence of a hypoplastic maxilla, increased
mandibular gonial, and increased mandibular body length.
The abnormal sella and presence of wormian bones were
the prominent findings in the skull.
The ground section revealed increased interprismatic
distance and focal areas of calcifications. The remaining teeth
specimens were decalcified in 10% Nitric acid, processed,
sectioned, and stained with the routine Hematoxylin and
Eosin stain. Examination of the stained sections revealed
multiple calcifications within the pulp chamber.
Figure 3: Intra-oral photograph shows partial ankyloglossia (arrow).
Case 2
A 14-year-old-girl also complained of worn out and
multiple missing teeth. The general physical examination
revealed a short stature (128 cm), short limbs, short ribs,
and dysplastic nails and teeth. An extra-oral examination
showed dolicocephalic, hypoplastic maxilla, frontal
bossing, receding hair line, antimongoloid slant of eyes, and
poor vision [Figure 5]. Her prenatal and natal histories were
uneventful and she had attained all the developmental
milestones at the appropriate time.
Figure 4: Orthopantomograph shows multiple unerupted teeth and missing
permanent tooth germs (black arrow), short roots (white arrow), and enlarged
pulpal chambers (dashed arrow).
An intra-oral examination revealed partial ankyloglossia,
widely spaced attrited teeth, discolored malformed
dentition with hypoplastic enamel, oligodontia, large pulp
chambers, and a collapsed bite [Figures 6a and 6b].
The OPG showed multiple impacted teeth, multiple
missing permanent tooth germs, retained teeth, short
roots, and enlarged pulp chambers [Figure 7]. A Hand-Wrist
Radiograph showed incomplete capping of the epiphysis
of the mid phalanx and incomplete fusion of the epiphysis
and diaphysis of the radius [Figure 8].
These findings indicated a skeletal abnormality associated
with the orofacial defect. After a thorough search and
symptomatic analysis the diagnosis was narrowed down
to two syndromes:
•
Weyers Acrofacial Dysostoses
•
EvC syndrome
These syndromes show a plethora of features among which
a few matched with the cases presented here.
DISCUSSION
The patients described here, had features common to
Journal of Clinical Imaging Science | Vol. 2 | Issue 1 | Apr-June 2012
Figure 5: Extra-oral photograph shows dolicocephalic, hypoplastic maxilla
(white arrow), with anti-mongoloid features (black arrow).
a
b
Figure 6: (a) Intra oral photograph of the maxillary arch shows multiple missing
teeth (b) Intra oral photograph shows ankyloglossia (arrow), widely spaced,
discolored, and malformed teeth.
EvC and Weyer’s Acrofacial dysostosis as elaborated in
Table 1.
3
Shetty, et al.: Weyer’s acrofacial dysostoses
Table 1: Comparative evaluation of features in the present cases with EvC syndrome and Weyers acrofacial dysostosis
Orofacial
Hypodontia
Conical teeth
Enlarged pulp chambers
Hypoplastic enamel
Natal teeth
Multiple frenulae
Ankyloglossia
Protruded mandible
Hair changes
Hypotelorism
Skeletal
Disproportionate dwarfism
Postaxial polydactyly
Hypoplastic nails
Brachydactyly
Hypoplastic thorax
Digital deformities
Systemic
Cardiac abnormalities
Retinal deformities
Renal
Pancreatic
Lethal in newborns
EvC syndrome
Weyers acrofacial dysostes
Case 1
Case 2
+
+
+
+
+
+
+
+/_
+/-
+
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Fusion of capitate and
hamate
Mild
+
+
+
Fusion of metatarsals and
metacarpals
+
-
+
-
-
-
-
+
+
+/-
-
Poor vision
-
Poor vision
-
Figure 7: Orthopantomograph shows multiple impacted teeth, multiple missing
permanent tooth germs, retained teeth (arrow), short roots (arrow), and enlarged
pulp chambers (arrow).
Ellis-van Creveld is an autosomal recessive skeletal dysplasia
characterized by short limbs, postaxial polydactyly, short
ribs, and dysplastic nails and teeth. Congenital cardiac
defects occur in 60% of the affected individuals and the
disease is mapped to chromosome 4p 16.[7]
The syndrome can be diagnosed during the prenatal
period, starting from the eighteenth week of gestation,
by ultrasonography, or later by clinical examination
after birth. [7] Chondrodysplasia is the most common
clinical feature affecting the tubular bones, resulting in
a serious ossification defect. In consequence, the distal
extremities of the limbs are short and the patient is
small in stature.[8] Baujat et al.,[7] have demonstrated that
the growth hormone therapy is not effective in these
patients. However, there is one published case that has
shown a favorable result in growth following hormonal
treatment.[8]
Orofacial digital syndromes present with variable and
4
Figure 8: Hand-wrist radiograph shows incomplete capping of the epiphysis
of the mid phalanx (small arrow) and incomplete fusion of the epiphysis and
diaphysis of the radius (large arrow).
overlapping phenotypic features, rendering this syndrome
difficult to classify and differentiate from other syndromes
of a similar clinical spectrum like EvC and Weyers syndrome.
It results from a dominant sex-linked inheritance; they are
limited to women and clinically characterized by multiple
gingivolabial frenula, hypoplasia of the nasal cartilages,
moderate mental retardation, fissured tongue, and in onethird of the cases ankyloglossia.[4,8]
In the year 1952, Weyers described a syndrome of postaxial
polydactyly, anomalies of the lower jaw, dentition,
and oral vestibule, and proposed the name ‘acrofacial
dysostosis’. He simultaneously suggested an autosomal
dominant inheritance of the disorder. The occurrence of nail
anomalies is non-obligatory and incomplete penetrance
has been suggested. Weyers acrofacial dysostoses (MIM
Journal of Clinical Imaging Science | Vol. 2 | Issue 1 | Apr-June 2012
Shetty, et al.: Weyer’s acrofacial dysostoses
193550) is considered a similar, but milder phenotype of
EvC and has been mapped in a single pedigree to an area
that is also a critical genomic region for the EvC syndrome
mutation. According to McKusick both these syndromes
are allelic conditions.[9]
characteristics. On account of the consanguinity of the
pedigree and the parents being healthy, a recessive pattern
of inheritance is highly probable in the present cases.
Ellis-van Creveld belongs to the short rib-polydactyly group
(SRP). These SRPs are all autosomal recessive disorders that
have been classified into various types (Saldino-Noonan
syndrome, Type I; Majewski syndrome, Type II; VermaNaumoff syndrome, Type III; Beemer-Langer syndrome,
Type IV; and Jeune Dystrophy). They are characterized by
hypoplastic thorax due to short ribs, short limbs, frequent
polydactyly, and visceral abnormalities, and are detected
prenatally. Radiographically and histologically, SRP III
(Verma-Naumoff syndrome, OMIM 263510) resembles
some forms of EvC.[10,7]
Proper systematic methodology is needed in classifying or
categorizing the syndromes discussed. Further case series are
required to exactly demarcate these syndromic conditions
from others, as the clinical spectrum of EvC and Weyers
syndrome is not well delineated at present. Molecular testing
in the affected individuals is required to ascertain whether
they have mutations in EVC or EVC2, and whether the
patients are homozygous or heterozygous for these changes.
The Ellis-van Creveld syndrome requires multidisciplinary
therapeutic planning. The odontologist plays a fundamental
role in the control of oral and dental manifestations. A
combination of orthodontics, surgery, and prosthetics is
essential to correct the craniofacial morphology and dental
defects, aiming to achieve satisfactory functional and
esthetic result. Dental treatment should be made under
low antibiotic prophylaxis due to the high incidence of
heart pathology in these patients.[7]
We emphasize the fact that cognitive development in the
syndromes described here is normal. Prognosis of the final
body height in individual patients is difficult to predict,
as a few publications have been reported in literature
on adult patients. Although postaxial polydactyly is a
constant clinical finding seen in both EvC and Weyers
syndrome, in the present cases this feature is not seen.
Therefore, the authors suggest the need for further
gene analysis that consider the possibility of mutation at
different gene loci.
CONCLUSION
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Source of Support: Nil, Conflict of Interest: None declared.
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