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OCULODENTODIGITAL DYSPLASIA- AN INTERESTING CASE
Mubeen K*, Vijyalaxmi KR*, Neera Ohri*
ABSTRACT:
Oculodentodigital dysplasia (ODDD) is a rare, autosomal dominant disorder with high penetrance and variable
expressivity, caused by mutations in the Connexin 43 (Cx43) or gap junction protein alpha-1 (GJA1) gene. It has
been diagnosed in fewer than 300 people worldwide. It affects many parts of the body particularly eyes (oculo),
teeth (dento), and fingers (digital). The common clinical features include facial dysmorphism with thin nose,
conductive deafness, microphthalmia, syndactyly, and tooth anomalies like enamel hypoplasia, anodontia,
microdontia and early tooth loss. Other less common features are abnormalities of the skin and its appendages, such
as brittle nails and sparse hair. To prevent this syndrome from being overlooked, awareness of possible symptoms is
necessary. Early recognition can prevent blindness, dental problems and learning disabilities. Described here is the
case of a 29 year male. Careful clinical re-evaluation revealed ODDD, characterised by the predominance of facial
and ophthalmological involvement with congenitally missing teeth.
AOSR 2011;1(1):26-29.
Key Words: Oculo-dento-digital dysplasia, syndactyly, microphthalmia, camptodactyly.
*Department of Oral Medicine and Radiology, Govt. Dental College & Research Institute, Bangalore 560002,
INDIA.
INTRODUCTION:
Oculo-dento-digital dysplasia (ODDD)
[MIM
*164200]), is an extremely rare autosomal dominant
disorder with high penetrance, variability expressivity,
and advanced paternal age in sporadic cases.1 It is also
known as oculodento-osseous syndrome or MeyerSchwickerath syndrome.2 This rare developmental
multisystemic disorder was first described by Lohmann
in 1920.3 Meyer-Schwickerath introduced the term
“dysplasia oculodentodigitalis” in 1957.4 Gorlin
established the acronym of ODDD syndrome in1963. 5
Approximately 300 such patients have been reported so
far, the majority of them being white.1,3
Ophthalmic
findings
include
microphthalmia,
microcornea, fine porous spongy iris abnormalities,
cataracts, glaucoma, and optic atrophy.6 Dental
abnormalities include microdontia, anodontia, multiple
caries, early tooth loss and mandibular overgrowth
with wide alveolar ridge and skeletal anomalies include
syndactyly, camptodactyly and clinodactyly due to
hypoplasia or aplasia of the middle phalanges.4,6
The typical craniofacial anomalies include a thin nose
with hypoplastic alae nasi, small anteverted nares,
prominent columnella, hyper- or hypotelorism, cranial
hyperostosis and microcephaly.4 ODDD patients also
have abnormalities of the skin and its appendages, such
as brittle nails, slowly growing hair, sparse, curly or
kinky hair and, very rarely, palmoplantar keratoderma. 3
Some cases have dysplastic ears and conductive
hearing loss.1
slowly progressive leukodystrophymay also be
present.1,6,7 Brain magnetic resonance imaging studies
of patients with ODDD have shown diffuse bilateral
abnormalities in the subcortical cerebral white matter,
which
can
define
a
slowly
progressive
leukodystrophy.1
Mutations in the connexin 43 gene or gap junction
protein alpha-1 gene (GJA1) located on chromosome
6q22-q24 leads to disruption of Cx43-mediated cell to
cell
communication
resulting
in
disrupted
morphological patterning during development and
altered functioning of cells in mature tissue. The gap
junction protein Cx43 is almost ubiquitously expressed
in various tissues of ectodermal and mesodermal
origin, which might explain the complex phenotype
and widespread organ involvement in ODDD.3
CASE REPORT:
A 29 year old male but with senile appearance
reported to Department of Oral Medicine and
Radiology with a chief complaint of loose denture
since 2 years. Patient gave history of denture wearing
since 24 years with no history of eruption of teeth. The
first denture was made when patient was 5 years old
and the dentures were remade on different occasions
according to the growth. He is the third child of nonconsanguineous healthy parents with no contributing
family history.
On General physical examination- The gait was ataxic
with moderate built & nourishment and other vital
signs were found to be in the normal range.
Neurological symptoms, such as mental delay, ataxia,
spasticity, neurogenic bladder disturbances and as
26
Oculodentodigital Dysplasia- A Rare Case Report
Examination of skin & its appendages revealed
icthyosis, dry, scaly skin, hypotrichosis (figure-1, A),
dystrophic and brittle nails (figure-1, B).
Examination of skeletal system: The hands revealed
camptodactyly of 4th and 5th fingers & syndyctaly of
thumb, 2nd and 3rd fingers (figure-2, A) .The feet
revealed syndyctly of 2nd to 5th toe and clinodactyly of
great toe (figure-2,B).
Figure- 4: The oral cavity showing (A) diffuse bluish
pigmentation of oral mucous membrane.
(B) Total anodontia and diffuse areas of inflammation
pertaining to the denture bearing surface.
Figure 1: (A) showing dry scaly skin and
hypotrichosis and
(B) showing dystrophic brittle nails.
Figure-5: Orthopantamograph showing completely
edentulous upper &lower arches with flattening of
alveolar ridges
Figure 2; (A) camptodactyly of 4th and 5th fingers &
syndyctaly of thumb, 2nd and 3rd fingers.
(B) syndyctly of 2nd to 5th toe & clinodactyly of great
toe.
Examination of face revealed dry lips, angular cheilitis
(figure-3, A), eyes appearing small & shrunken with
sparse eyebrows, short palpebral fissures (figure-3, B),
trichiasis and pale blue irids, nose showed prominent
columella (figure-3, C).
Examination of oral cavity showed diffuse bluish
pigmentation of oral mucous membrane (figure-4,A).
Patient was also found to have total anodontia and
diffuse areas of inflammation pertaining to the denture
bearing surface on palate, suggestive of denture
induced stomatitis (figure-4 B).
Combining all these features, a provisional diagnosis of
hypohidrotic anhidrotic Ectodermal dysplasia with
denture induced stomatitis was made.
Differential diagnosis of Hallermann– Streiff
syndrome, Orofacial digital syndrome type II,
Keratitis-ichthyosis-deafness
(KID)
syndrome,
Ectrodactyly-ectodermal dysplasia-clefting (EEC)
Syndrome and Occulo-dento-digital dysplasia was
considered.
Figure-3: Face showing (A) dry lips, angular cheilitis
(B) eyes appearing small & shrunken with sparse
eyebrows, short palpebral fissures and
(C) trichiasis, pale blue irids and prominent columella.
Patient was further screened with orthopantamograph,
which confirmed completely edentulous upper &lower
arches with flattening of alveolar ridges (figure-5).
Considering our differential diagnosis patient was
further referred for ophthalmological examination
which revealed additional significant findings like mild
hypertelorism, entropian, micro-cornea, symbelpharon,
diminished visual acuity and reduced tear secretion.
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Mubeen K et al.
The patient was also being evaluated for hearing loss in
the department of ENT, where he was advised an
audiogram which revealed conductive hearing loss of
left ear.
Taking into consideration, the clinical features of
patient, combining the valuable opinion of the
concerned specialities and having a retrospective look
on literature a clinical diagnosis of Oculo-dento-digital
dysplasia with denture induced stomatitis was made.
Patient was prescribed antifungal agents for denture
stomatitis and occlusal rehabilitation was done.
DISCUSSION:
Oculodentodigital dysplasia (ODDD) is a
disorder with distinct clinical features affecting both
ectodermal and mesodermal cell lineages. The
developmental abnormalities in ODDD appear to be
caused by impaired Cx43 function during
embryogenesis and epithelial differentiation.3
Gap junctions are clusters of intercellular channels that
permit the diffusional exchange of ions, small
metabolites, nutrients, and signaling molecules
between adjoining cells. Gap junction intercellular
communication controls and coordinates an abundance
of cellular activities. It is crucial for tissue
morphogenesis and homeostasis, cell growth,
differentiation, response to stimuli, and fulfils many
other tissue-specific functions In humans, the gap
junction system is formed by a polygenic family of
more than 20 different connexin proteins named by
their predicted molecular mass. All connexins are
integral membrane protein. Six connexin molecules are
assembled into oligomers called connexon, which are
transported to the cell membrane and aggregate into
gap junction plaques. 8
Cx43 is expressed in various tissues such as brain,
heart, gonads, lens, cornea, skin and bone. Reduction
of Cx43 expression in animal models resulted in
microphthalmia and a smaller retina.9 These data
correspond well with the ocular abnormalities in
ODDD like microcornea, as well as microphthalmia
seen in our patient. In the postnatal tooth development
of rats, Cx43 channels have been demonstrated
between the odontoblasts and appeared to be necessary
for the secretion of the dentin matrix.10
The demonstration of a genetic linkage of the
oculodentodigital dysplasia (ODDD) to the GJA1 locus
offers the strongest evidence for a critical role of Cx43
in skeletal development. To date, at least 24 distinct
point mutations of GJA1 have been identified in
subjects with this disease.11
GJA1 missense mutations found in ODDD have a
dominant negative effect. The complex combinatorial
interactions among the connexins suggest that
additional mutational analysis of connexins other than
connexin 43 in ODDD patients may give us insights
into which specific connexions may modify the
functional consequences of the GJA1 missense
mutations. 1
There are many conditions mentioned in literature with
overlapping features as in ODDD.These include: EEC
syndrome, Hallermann– Streiff syndrome, Orofacial
digital syndrome Type II, KID syndrome etc. The EEC
syndrome is characterised by ectrodactyly or lobsterclaw deformity, ectodermal dysplasia, and cleft lip and
palate. It is a rare disorder with autosomal dominant
inheritance, variable expression, and in some families
lack of penetrance.12 Cleft lip/palate is present in most
patients, and in those without cleft lip/palate the
philtrum or uvula or both are often abnormal. 13 The
cleft lip/palate was not present in our patient and
significant eye changes and facial features favouring
ODDD were present.
Hallermann-Streiff Syndrome (HSS) is a rare disorder
characterized primarily by head and face abnormalities,
with dental abnormalities also present in 50-80 percent
of cases. Seven essential signs were described by
Francois as diagnostic criteria for HSS these includedyscephalia and bird-like facies, abnormal dentition,
hypotrichosis, atrophy of skin especially on the nose,
Congenital cataracts, Bilateral microphthalmia and
Proportionate dwarfism.hss2. The digital changes like
syndactyly or camptodactyly like ODDD is not present
in this syndrome.14
The Mohr-Claussen syndrome or oro-facial-digital
syndrome type II (OFD-II)] is transmitted as an
autosomal recessive and is characterized by
malformation of face, oral cavity and digits. Facial and
oral features include frontal bossing, facial asymmetry,
broad nasal bridge, cleft upper lip and cleft palate,
lobulated tongue. Digital features include clinodactyly,
syndactyly, brachydactyly, pre- and post-axial
polydactyly and duplication of the first toe. Other
systemic features include conductive deafness,
congenital heart defects and renal abnormalities. in
variable combination. Diagnosis is mainly clinical.15
There are usually no eye manifestations and skin
changes as seen in ODDD.
Keratitis-ichthyosis-deafness (KID) syndrome is the
most severe cutaneous connexin disorder because of
the involvement of several epithelia of ectodermal
origin, including skin, appendages, nail, teeth, inner
ear, and cornea. Most of the cases are sporadic
(N90%), but examples of autosomal dominant or
potentially recessive transmission have been reported.
The
majority
develops
symmetrical,
well-
28
Oculodentodigital Dysplasia- A Rare Case Report
circumscribed hyperkeratotic plaques with underlying
erythema
on
the
extremities
and
face
(erythrokeratoderma). In others, the skin is thickened
and has a coarse-grained appearance or shows filiform
follicular hyperkeratoses without erythema. With very
few exceptions, palms and soles are hyperkeratotic
with a rough, stippled, or grainy-appearing surface.
Chronic cheilitis and perle`che are common, whereas
hair and nail dystrophy, scarring alopecia, dental
anomalies, and heatintolerance are less frequent.8
Roughly 96% of patients with KID syndrome also
develop during childhood ophthalmologic problems,
such as corneal neovascularization, chronic blepharitis,
and conjunctivitis, which may cause progressive visual
decline and blindness. Most consistent is the finding of
sensorineural hearing loss, which is often congenital,
bilateral, and severe to profound whereas in ODDD
hearing loss is conductive. In KID syndrome there are
no digital manifestations as seen in ODDD.8
The broad clinical overlap between these genetic
disorders likely stems from the shared tissue
expression and function of cutaneous connexins.
Molecular diagnostic and prenatal testing for these
connexin disorders has become available and certainly
aids in establishing a correct diagnosis.
CONCLUSION:
This rarest entity poses a diagnostic challenge
for the clinician and the awareness of possible
symptoms is necessary to arrive at one. Early
recognition can prevent significant co- morbidities in
the form of blindness, deafness and learning disabilities
which can severely affect the quality of life in this
condition. We as an oral physician can significantly
contribute in bringing the smile on the face of these
patients.
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Correspondence: Dr. Neera Ohri
Department of Oral Medicine and Radiology,
Government Dental College and Research
Institute, Fort, Bangalore-560002, Karnataka,
India.E-mail: [email protected]
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