New oral findings in Cohen syndrome

Carlos Garcı́a-Ballesta, MD, DDS,a Leonor Pérez-Lajarı́n, MD, DDS,a Olga Cortés Lillo, DDS,a
and Luis Alberto Bravo-González, MD, DDS,a Murcia, Spain
UNIVERSITY OF MURCIA

Cohen syndrome is a hereditary disorder transmitted as an autosomal-recessive trait. Approximately 100 cases
have been reported in the genetic and pediatric literature. Despite the fact that oral alterations are often observed in
these cases, only 1 work has been published addressing this specific topic, and it tended to concentrate on periodontal
abnormalities. The present study details 2 new patients, 2 brothers (8 and 11 years old), and mainly consists of an
analysis of the dentomaxillary anomalies that until now have not been studied in depth. In this study, the mandible,
characterized as hypoplastic in Cohen syndrome, appears to be in a normal position; what really exists is a maxillary
hyperplasia of genetic origin. We also put forward an observation hitherto undescribed in the literature: dental
agenesis.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:681-87)

In 1973, Cohen et al1 described a new syndrome

whose main features were obesity, hypotonia, mental
retardation, characteristic craniofacial dysmorphism,
and abnormalities of the hands and feet. In 1978, Carey
and Hall2 confirmed the existence of this entity and
added fresh observations. Thus, the manifestations of
Cohen syndrome were established.3
The syndrome is a hereditary disorder transmitted as
an autosomal-recessive trait, with considerable vari-
ability of expression. Cases have been reported in sib-
lings, sometimes with consanguineous parents,4 and 1
case of transmission by an autosomal-dominant mode
has also been published.5 Tahvanainen et al6 and Hilton
et al7 identified the locus of Cohen syndrome in chro-
mosome 8q22-q24.
The pathogenic mechanism of Cohen syndrome is
unknown, but involvement of the connective tissue,
muscle, brain, retina, and occasionally the hematopoi-
etic system8 suggest a possible metabolic alteration or
an alteration of the connective tissue itself as the origin
of the problem, as was suggested by Friedman and
Sack.9
Since Cohen syndrome was first described, close to
100 cases have been reported, the majority in the ge-
netic and pediatric literature. Despite the fact that oral
anomalies are pathognomonic of Cohen syndrome, few
studies in the literature have addressed the oral mani-
festations, and these have addressed only the periodon-
tal alterations.10,11

Fig 1. Patient 1, an 8-year-old boy.

a
Professor, The Department of Pediatric Dentistry and Orthodontics,
University of Murcia.
Received for publication Sep 5, 2002; returned for revision Oct 30,
2002; accepted for publication Dec 23, 2002.
© 2003, Mosby, Inc. All rights reserved.
Here we describe 2 new patients, analyze their oral
1079-2104/2003/$30.00 ⫹ 0 anomalies, which until now have not been studied in
doi:10.1067/moe.2003.138 depth, and make a new observation regarding sporadic

681
682 Garcı́a-Ballesta et al ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003

Fig 2. Note the prominent central incisors and areas of hypomineralization.

Fig 3. Panoramic radiograph of patient 1. Agenesis of the upper lateral incisors and the upper and lower second premolars can
be observed.

presentation. Two brothers (8 and 11 years old) with a
clinical diagnosis of Cohen syndrome, with healthy
nonconsanguineous parents, and without any relevant
family antecedents are studied.
CASE 1
An examination was performed on an 8-year-old boy without
pathologic alterations whose main phenotypic features were
obesity; faciotruncal predominance starting to develop at 5
years of age; a dysmorphic face with narrow forehead and
high nasal bridge; small hands with long, thin fingers; small
feet; muscular hypotonia that had been more severe in in-
fancy; moderate mental retardation; and ocular anomalies
(Fig 1). The results of hematologic and endocrinologic studies
of the hypothalamus-hypophysis-gonad-thyroid– growth hor-
mone axis were normal. During a craniofacial examination,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Volume 95, Number 6
Fig 4. Cephalometric analysis of patient 1.
the following features were observed: microcephaly and
down-slanted palpebral fissures. An extraoral examination
revealed micrognathia, an open mouth, and prominent and
separated upper central incisors (Fig 2). Both incisors had
areas of hypomineralization in the vestibular surface. A pan-
oramic radiograph revealed agenesis of the upper lateral in-
cisors and of the upper and lower second premolars (Fig 3).
A radiologic determination of bone loss was undertaken by
measuring millimetrically the space between the cementoe-
namel junction and the alveolar crest; the values were found
to be within normal ranges (ie, up to 2 mm).
Cephalometric data were obtained from lateral radiographs,
with the patient in a standing position, the teeth in occlusion,
and the lips relaxed. The cephalometric radiographs were
traced by the same person (L.A.B.-G.) and digitized with a
Gridmaster digitizer (Numonics Corporation, Montgomer-
yville, Pa) linked to an SE/30 Macintosh computer (Apple
Computer, Cupertino, Calif) running Quick-Ceph II software
(Orthodontic Processing, Chula Vista, Calif). The magnifica-
Garcı́a-Ballesta et al 683
tion factor of the linear measurements was determined for
each radiograph and was corrected by using the cephalomet-
ric software. Steiner’s and Rickets’ methods were used in the
cephalometric analysis. Severe prognathia of the maxilla was
discovered; however, the mandible was found to be in a more
normal position (SNA ⫽ 89.5°; SNB ⫽ 82.9°) (Fig 4). The
face was severely dolichofacial, and a moderate to severe
skeletal Class II, Division 1 malocclusion was observed.
The intraoral examination revealed the following main
characteristics: The patient was in the first phase of mixed
dentition, with a molar and canine distoclusion (Class II,
Division 1), with pronounced protrusion (4 mm) and a high
arched palate. He also had a high score on the O’Leary
Plaque Index (ie, 45% of the surfaces were stained) and a
moderate degree of gingivitis.
CASE 2
An 11-year-old boy, brother to the first patient described here,
had the same phenotypic features as his brother; however, he
684 Garcı́a-Ballesta et al ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003

Table. Features of Cohen syndrome from Pérez Cabal-

lero18
Manifestation References
Autosomal recessive 100
Open mouth 83
Maxillary hypoplasia 80
Micrognathia 80
High nasal bridge 80
Short philtrum 80
High arched palate 80
Dental malocclusion 80
Prominent central incisors 80
Hyperextended joints 80
Thin fingers 80
Narrow hands and feet 80
Delayed puberty 80
Mental retardation 80
Hypotonia 80
Truncal obesity 80
Short stature 80
Strabismus 61
Microcephaly 50
Down-slanted palpebral fissures 50
Dysplastic ears 50
Cubitus valgus 50
Crytporchidich hypoplastic testicles 50
Hyphoscoliosis 38
Microphthalmia 10
Coloboma 10
Mottled retinal pigment 10
Finger syndactyly 10

Fig 5. Patient 2, the 11-year-old brother of patient 1.

Fig 6. Panoramic radiograph of patient 2.

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
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Fig 7. Cephalometric analysis of patient 2A.
also had a transverse palmar fold, articular hyperelasticity,
and greater mental retardation than his brother (Fig 5).
Craniofacially, a broad nasal root, short philtrum, down-
slanted palpebral fissures, and thick lips with labial incompe-
tence were observed.
The patient was in the last phase of mixed dentition,
without a high arched palate in this case. The occlusal exam-
ination revealed the permanent molar relationship as Class I.
He had a high plaque index value (ie, 65% of the surfaces
were stained) and a gingivoperiodontal state of moderate to
severe grade. A radiographic examination revealed only the
absence of germs of third molars (Fig 6). Bone-loss values
were within normal ranges. Cephalometric analysis showed
severe maxillary prognathia and moderate mandibular prog-
Garcı́a-Ballesta et al 685
nathia (SNA ⫽ 85.7°; SNB ⫽ 80.8°; Fig 7). The facial type
could be described as mesiofacial with a brachyfacial ten-
dency; sagittally, a light skeletal Class II, Division 1 maloc-
clusion was present.
DISCUSSION
Several familial syndromes have been described in
which mental retardation, obesity, short stature, and
craniofacial anomalies are connected. Cohen syn-
drome, sometimes called Pepper syndrome, must be
differentiated from other syndromes such as Prader-
Willi12 and Laurence-Moon syndrome.13 However, in
Cohen syndrome, the phenotype with strict clinical
686 Garcı́a-Ballesta et al
criteria is extremely difficult to establish. This is be-
cause a wide variety of manifestations exist, which
raises the possibility that not all of them correspond to
the same process. It has been suggested that there are
2 types of Cohen syndrome, 1 with neutropenia and
1 without neutropenia.14 Therefore, in young persons
with hypotonia and motor-development retardation, he-
matologic screening for leukemia/neutropenia should
be a routine procedure, because these defects are
present from birth.15
However, in our 2 patients, no anomalies were ob-
served in the hematopoiesis. Although close to 100
cases have been reported in the medical literature, the
terminology used to describe dentomaxillary anomalies
remains imprecise, including, among other descrip-
tions, “dental chaos, prominent incisors, open mouth
and maxillary hypoplasia.”15,16 They are all highly
significant, yet these anomalies have not been studied
in detail, probably because they were described in the
pediatric or genetic literature.
The term “dental chaos,” which we suppose refers to
a positive dentomaxillary discrepancy (a condition that
is present in 80% of patients), is not precisely a signif-
icant alteration in young children because a similar
percentage of the child population has this to some
degree.16 In our 2 patients, we saw no evidence of
dental crowding.
The term “high arched palate,” on the other hand, is
very subjective. In fact, difficulty arises in the compar-
ison and contrast of those with and without this char-
acteristic because the term does not suggest any patho-
sis and because, in 14% of the Spanish population, it
appears as a phylogenetic characteristic with no sug-
gestion of any anomaly.17 Indeed, in our 2 patients,
1 boy presented with what we could describe as a high
arched palate while the other boy did not.
With respect to the term “maxillary hypoplasia,”
which is listed in 80% of the relevant literature as being
part of the syndrome,9,14,18,19 we suppose that mandib-
ular hypoplasia is what is meant. This represents a
disagreement in semantics. However, in none of the
cases described was cephalometric analysis performed
to prove the existence of such hypoplasia. By means of
an analysis similar to those used by Steiner and Rickets,
we have obtained values that lead us to believe that not
only is mandibular hypoplasia not present but also the
mandible is in a normal position. Furthermore, we
found that maxillary hyperplasia and, consequently,
labial incompetence were present genetically. The pres-
ence of “prominent incisors,” a term appearing fre-
quently in the literature, is no more than the conse-
quence of maxillary prognathia and labial interposition.
With regard to the appearance of dental agenesis in
1 of our 2 patients, a review of the literature reveals that
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003
orthopantomography was performed in only 1 study.10
Consequently, these authors were able to confirm the
existence of this entity. A radiologic examination could
be performed in only 12 of the 15 patients in this study.
Only 2 of the 15 were children (14 and 15 years of age,
with all teeth present). The adult patients (range, 20-57
years of age) displayed considerable hypodontia. This
might be attributable to either exodontia or to a con-
genital absence of tooth germs. A larger number of
nonadult patients and the performance of a buccal ra-
diographic examination are necessary to discover
whether the aforementioned anomaly (absence of tooth
germs) is a part of Cohen syndrome or is merely a
casual finding.
We used the O’Leary Plaque Index because of its
objectivity, whereas Alaluusua et al10 performed a pho-
tographic clinical evaluation. Their results were similar
to ours with respect to the state of oral hygiene. In our
gingivoperiodontal evaluation, the results again coin-
cided with those of Alaluusua et al10 in that the gingival
status was of moderate to severe grade. We also radio-
logically evaluated the degree of bone loss from the
cementoenamel junction as far as the alveolar crest.
Despite the fact that their 2 young patients had neutro-
penia, Alaluusua et al10 did not find any evidence of
bone loss; neither did we find any evidence of bone loss
in our 2 patients, who did not have neutropenia.
In terms of craniofacial anomalies, our observations
appear to coincide with those of the other published
studies (Table). We can see the main features of Cohen
syndrome.20
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Reprint requests:
Carlos Garcı́a Ballesta, MD, DDS
Hospital Morales Meseguer
Facultad de Odontologı́a
Avenida Marqués de los Vélez s/n30.008
Murcia, Spain
cgarcia@um.es