Professional Documents
Culture Documents
New Oral Findings in Cohen Syndrome: (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003 95:681-87)
New Oral Findings in Cohen Syndrome: (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003 95:681-87)
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)
681
682 Garcı́a-Ballesta et al ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003
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 obesity; faciotruncal predominance starting to develop at 5
clinical diagnosis of Cohen syndrome, with healthy years of age; a dysmorphic face with narrow forehead and
nonconsanguineous parents, and without any relevant high nasal bridge; small hands with long, thin fingers; small
family antecedents are studied. feet; muscular hypotonia that had been more severe in in-
fancy; moderate mental retardation; and ocular anomalies
CASE 1 (Fig 1). The results of hematologic and endocrinologic studies
An examination was performed on an 8-year-old boy without of the hypothalamus-hypophysis-gonad-thyroid– growth hor-
pathologic alterations whose main phenotypic features were mone axis were normal. During a craniofacial examination,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Garcı́a-Ballesta et al 683
Volume 95, Number 6
the following features were observed: microcephaly and tion factor of the linear measurements was determined for
down-slanted palpebral fissures. An extraoral examination each radiograph and was corrected by using the cephalomet-
revealed micrognathia, an open mouth, and prominent and ric software. Steiner’s and Rickets’ methods were used in the
separated upper central incisors (Fig 2). Both incisors had cephalometric analysis. Severe prognathia of the maxilla was
areas of hypomineralization in the vestibular surface. A pan- discovered; however, the mandible was found to be in a more
oramic radiograph revealed agenesis of the upper lateral in- normal position (SNA ⫽ 89.5°; SNB ⫽ 82.9°) (Fig 4). The
cisors and of the upper and lower second premolars (Fig 3). face was severely dolichofacial, and a moderate to severe
A radiologic determination of bone loss was undertaken by skeletal Class II, Division 1 malocclusion was observed.
measuring millimetrically the space between the cementoe- The intraoral examination revealed the following main
namel junction and the alveolar crest; the values were found characteristics: The patient was in the first phase of mixed
to be within normal ranges (ie, up to 2 mm). dentition, with a molar and canine distoclusion (Class II,
Cephalometric data were obtained from lateral radiographs, Division 1), with pronounced protrusion (4 mm) and a high
with the patient in a standing position, the teeth in occlusion, arched palate. He also had a high score on the O’Leary
and the lips relaxed. The cephalometric radiographs were Plaque Index (ie, 45% of the surfaces were stained) and a
traced by the same person (L.A.B.-G.) and digitized with a moderate degree of gingivitis.
Gridmaster digitizer (Numonics Corporation, Montgomer-
yville, Pa) linked to an SE/30 Macintosh computer (Apple CASE 2
Computer, Cupertino, Calif) running Quick-Ceph II software An 11-year-old boy, brother to the first patient described here,
(Orthodontic Processing, Chula Vista, Calif). The magnifica- had the same phenotypic features as his brother; however, he
684 Garcı́a-Ballesta et al ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003
also had a transverse palmar fold, articular hyperelasticity, nathia (SNA ⫽ 85.7°; SNB ⫽ 80.8°; Fig 7). The facial type
and greater mental retardation than his brother (Fig 5). could be described as mesiofacial with a brachyfacial ten-
Craniofacially, a broad nasal root, short philtrum, down- dency; sagittally, a light skeletal Class II, Division 1 maloc-
slanted palpebral fissures, and thick lips with labial incompe- clusion was present.
tence were observed.
The patient was in the last phase of mixed dentition, DISCUSSION
without a high arched palate in this case. The occlusal exam-
Several familial syndromes have been described in
ination revealed the permanent molar relationship as Class I.
He had a high plaque index value (ie, 65% of the surfaces
which mental retardation, obesity, short stature, and
were stained) and a gingivoperiodontal state of moderate to craniofacial anomalies are connected. Cohen syn-
severe grade. A radiographic examination revealed only the drome, sometimes called Pepper syndrome, must be
absence of germs of third molars (Fig 6). Bone-loss values differentiated from other syndromes such as Prader-
were within normal ranges. Cephalometric analysis showed Willi12 and Laurence-Moon syndrome.13 However, in
severe maxillary prognathia and moderate mandibular prog- Cohen syndrome, the phenotype with strict clinical
686 Garcı́a-Ballesta et al ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
June 2003
criteria is extremely difficult to establish. This is be- orthopantomography was performed in only 1 study.10
cause a wide variety of manifestations exist, which Consequently, these authors were able to confirm the
raises the possibility that not all of them correspond to existence of this entity. A radiologic examination could
the same process. It has been suggested that there are be performed in only 12 of the 15 patients in this study.
2 types of Cohen syndrome, 1 with neutropenia and Only 2 of the 15 were children (14 and 15 years of age,
1 without neutropenia.14 Therefore, in young persons with all teeth present). The adult patients (range, 20-57
with hypotonia and motor-development retardation, he- years of age) displayed considerable hypodontia. This
matologic screening for leukemia/neutropenia should might be attributable to either exodontia or to a con-
be a routine procedure, because these defects are genital absence of tooth germs. A larger number of
present from birth.15 nonadult patients and the performance of a buccal ra-
However, in our 2 patients, no anomalies were ob- diographic examination are necessary to discover
served in the hematopoiesis. Although close to 100 whether the aforementioned anomaly (absence of tooth
cases have been reported in the medical literature, the germs) is a part of Cohen syndrome or is merely a
terminology used to describe dentomaxillary anomalies casual finding.
remains imprecise, including, among other descrip- We used the O’Leary Plaque Index because of its
tions, “dental chaos, prominent incisors, open mouth objectivity, whereas Alaluusua et al10 performed a pho-
and maxillary hypoplasia.”15,16 They are all highly tographic clinical evaluation. Their results were similar
significant, yet these anomalies have not been studied to ours with respect to the state of oral hygiene. In our
in detail, probably because they were described in the gingivoperiodontal evaluation, the results again coin-
pediatric or genetic literature. cided with those of Alaluusua et al10 in that the gingival
The term “dental chaos,” which we suppose refers to status was of moderate to severe grade. We also radio-
a positive dentomaxillary discrepancy (a condition that logically evaluated the degree of bone loss from the
is present in 80% of patients), is not precisely a signif- cementoenamel junction as far as the alveolar crest.
icant alteration in young children because a similar Despite the fact that their 2 young patients had neutro-
percentage of the child population has this to some penia, Alaluusua et al10 did not find any evidence of
degree.16 In our 2 patients, we saw no evidence of bone loss; neither did we find any evidence of bone loss
dental crowding. in our 2 patients, who did not have neutropenia.
The term “high arched palate,” on the other hand, is In terms of craniofacial anomalies, our observations
very subjective. In fact, difficulty arises in the compar- appear to coincide with those of the other published
ison and contrast of those with and without this char- studies (Table). We can see the main features of Cohen
acteristic because the term does not suggest any patho- syndrome.20
sis and because, in 14% of the Spanish population, it
appears as a phylogenetic characteristic with no sug- REFERENCES
gestion of any anomaly.17 Indeed, in our 2 patients, 1. Cohen MM Jr, Hall BD, Smith DW, Graham CB, Lampert KJ. A
new syndrome with hypotonia, obesity, mental deficiency, and
1 boy presented with what we could describe as a high facial, oral, ocular, and limb anomalies. J Pediatr 1973;83:280-4.
arched palate while the other boy did not. 2. Carey JC, Hall BD. Confirmation of the Cohen syndrome. J Pe-
With respect to the term “maxillary hypoplasia,” diatr 1978;93:239-44.
3. McKusick VA. Mendelian inheritance in man. 7th ed. Baltimore:
which is listed in 80% of the relevant literature as being The John Hopkins University; 1986. p. 897-98.
part of the syndrome,9,14,18,19 we suppose that mandib- 4. Arcas Martinez J, Garcı́a Penas JJ, Ramos Lizana J, Dı́az Gonza-
ular hypoplasia is what is meant. This represents a lez C, Pascual Castroviejo I. Sı́ndrome de Cohen: presentación
de dos casos de gemelas. An Esp Pediatr 1991;34:83-5.
disagreement in semantics. However, in none of the 5. Mejia-Baltodano G, Bobadilla L, Solı́s A, Mendoza R, Dı́az-
cases described was cephalometric analysis performed Gallardo MY, Barros-Nunez P. A familiar syndrome with hypo-
to prove the existence of such hypoplasia. By means of tonia, mental retardation and dysmorphic features resembling
Cohen syndrome. Genet Couns 1997;8:311-6.
an analysis similar to those used by Steiner and Rickets, 6. Tahvanainen E, Norio R, Karila E, Ranta S, Weissenbach J,
we have obtained values that lead us to believe that not Sistonen P, et al. Cohen syndrome gene assigned to the long
only is mandibular hypoplasia not present but also the arm of chromosome 8 by linkage analysis. Nat Genet 1994;
7:201-4.
mandible is in a normal position. Furthermore, we 7. Hilton MJ, Gutierrez L, Zhang L, Moreno PA, Reddy M, Brown
found that maxillary hyperplasia and, consequently, N, et al. An integrated physical map of 8q22-q24: use in posi-
labial incompetence were present genetically. The pres- tional cloning and deletion analysis of Langer-Giedion syn-
drome. Genomics 2001;71:192-9.
ence of “prominent incisors,” a term appearing fre- 8. Norio R, Raitta C, Lindahl E. Further delineation of the Cohen
quently in the literature, is no more than the conse- syndrome; report on chorioretinal dystrophy, leukopenia and
quence of maxillary prognathia and labial interposition. consanguinity. Clin Genet 1984;25:1-14.
9. Friedman E, Sack J. The Cohen syndrome: report of five new
With regard to the appearance of dental agenesis in cases and a review of the literature. J Craniofac Genet Dev Biol
1 of our 2 patients, a review of the literature reveals that 1982;2:193-200.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Garcı́a-Ballesta et al 687
Volume 95, Number 6
10. Alaluusua S, Kivitie-Kallio S, Wolf J, Haavio ML, Asikainen S, 17. Facal Garcı́a M, Yagüe Facal R, de Nova Garcı́a J. Growth of
Pirinen S. Periodontal findings in Cohen syndrome with chronic dental arches during the stage of primary dentition. Rev Col
neutropenia. J Periodontol 1997;68:473-8. Odonto Estomatol 2001;6:397-404.
11. Seow WK, Bartold PM, Thong YH, Taylor K. Cohen syndrome 18. Wilson S, Escobar V, Hersh JH, Haskell BS. Cohen syndrome:
with neutropenia-induced periodontitis managed with granulo- case report. Pediatr Dent 1985;7:326-8.
cyte colony-stimulating factor (G-CSF): case reports. Pediatr 19. Calzolari S, Ballardini M, De Marco P. Sindrome di Cohen. Un
Dent 1998;20:350-4. nuova caso e revisione della letteratura. Minerva Pediatr 1995;
12. Laurance BM, Brito A, Wilkinson J. Prader-Willi syndrome after 47:83-7.
15 years. Arch Dis Child 1981;56:181-6. 20. Pérez-Caballero Macarron C, Lozano Giménez C, Quintana
13. Smith DW. Recognizable patterns of human malformations: ge- Castilla A, Aparicio Meix JM. Cohen’s syndrome: non-causal
netic, embryologic, and clinical aspects. 2nd ed. Philadelphia: association with vascular rings. An Esp Pediatr 2000;52:289-95.
W. B. Saunders Company; 1976. p. 86-7.
14. Norio R. Cohen syndrome is neither uncommon nor new. Am J
Med Genet 1994;53:202-3. Reprint requests:
15. Fryns JP, Legius E, Devriendt K, Meire F, Standaert L, Baten E,
Carlos Garcı́a Ballesta, MD, DDS
et al. Cohen syndrome: the clinical symptoms and stigmata at a
Hospital Morales Meseguer
young age. Clin Genet 1996;49:237-41.
16. Marin Ferrer JM, Barberı́a Leache E, Moreno Gonzĺez JP, Facultad de Odontologı́a
Planells del Pozo P, de Nova Garcı́a J, Costa Ferrer F. Study of Avenida Marqués de los Vélez s/n30.008
mesiodistal diameters in permanent dentition in Spanish child Murcia, Spain
population. Odontol Pediatr 1993;2:67-76. cgarcia@um.es