Craniofacial and oral manifestations of trichorhinophalangeal syndrome type I (Giedion's syndrome) A case report Guillermo Machuca, MD, DMD, a Francisco Marffnez, MD, DMD, b Carmen Machuca, MD, DMD, MPH, MSD, c and Pedro B u l l d n , MD, DMD, d Seville, Spain UNIVERSITY OF SPAIN, SCHOOL OF DENTISTRY
A case of trichorhinophalangeal syndrome type I (Giedion's syndrome) is presented and discussed. Pathologic alterations, including oral and facial manifestations, and the clinical history of this unusual condition are described. The case is compared with others reported in the literature. (Oral Surg Oral Ned Oral Pathol Oral Radiol Endod 1997;84:35-9)
A m o n g the genetic skeletal dysplasias, there are a series of syndromes with defects in growth of either the tubular bones, the spinal column, or both. The tric h o r h i n o p h a l a n g e a l s y n d r o m e type I (TRP I) or Giedion's syndrome can be classified as one of these syndromes. Patients affected with this disease have disproportionate short stature, finger deformities, and dysmorphic facial features including sparse hair, a pyriform-shaped nose, and medially thick eyebrows. The epiphyses of the fingers are cone-shaped. In addition, there are usually alterations of the hips of the LeggPerthes disease type (avascular necrosis of the proximal femur, with limpness or limitation of motion). The denomination TRP I is necessary to differentiate this syndrome from TRP II or Langer-Giedion syndrome. TRP II is a genetic skeletal dysplasia with abnormal d e v e l o p m e n t of cartilage tissue in which there is a greater number of malformations, as well as mental retardation in most cases. 1,2 This article reports the features of a case of TRP I. In addition to describing the clinical and genetic characteristics, the results of a cephalometric analysis are presented.
CASE REPORT A girl 12.years 5 months old was admitted to the University Dental Clinic of the Faculty of Dentistry, University of This article was reviewed by the Oral Diagnosis section of the Editorial Review Board. aAssociated Professor, Department of Oral Medicine and Periodontics,'University of Seville, School of Dentistry. bOrthodontics, private practice. CAssistantProfessor, Department of Oral Medicine and Periodontics, University of Seville, School of Dentistry. dprofessor and Chairman, Department of Oral Medicine and Periodontics, University of Seville, School of Dentistry. Received for publication Oct. 4, 1996; returned for revision Nov. 14, 1996; accepted for publication Feb. 21, 1997. Copyright © 1997 by Mosby-Year Book, Inc. 1079-2104/97/$5.00 + 0 7/17181822
Seville (Spain) in October 1995 for diagnosis and treatment of problems with her mouth. Her clinical history included the following features. She had been born at about 36 weeks gestation after a well-tolerated pregnancy; her birth weight was 3000 gm. She had had neonatal jaundice but nursing and subsequent feeding had progressed normally. She had the usual childhood illnesses with frequent febrile episodes. She underwent adenoidectomy at the age of 5 years. On examination she was lively and cooperative, and her psychomotor development was normal for her age. Her weight and height placed her in the 50 to 75 percentile, and her body habitus was normal. There were, however, some dysmorphic facial features such as sparse, thin, and fragile hair with an abnormal pigmentation starting high in the frontal area. In addition, there was oxycephaly with a high forehead and frontal protuberance. Her face was large and long, particularly in the middle section, and her nose was rather wide and pyriform in shape. Although the pinnae of her ears were normal in shape and position, they did protrude. Her eyebrows were small but were rather thick medially (Fig. 1). There were also abnormalities of her hands and feet: shortening of the first digit in both extremities with brachymetacarpia and brachymetatarsia (Fig. 2). Clinically there was very little impairment of function. Her gait was abnormal with kyphoscoliosis and asymmetry in the alignment of her hips. External examination of her mouth and perioral tissues showed a long philtrum (Fig. 1) and mild prognathism. Intraoral examination, with the teeth occluded, showed a posterior cross-bite and a mild degree of hypoplasia of the maxilla (Fig. 3). In addition, the upper and lower permanent incisors were malpositioned, deciduous teeth A, C, H, J, K, and T were retained, the left maxillary permanent first molar was partially erupted, and the right and left maxillary and mandibular second molars had not yet erupted; these conditions reflect some delay in the dental change-over. The most severe eruption abnormality was the partial eruption of the right and left maxillary canines in the vestibular area of the maxilla. Caries were present in the left and right mandibular first molars, which had posterior fillings (Figs. 4 and 5). The patient's family history was as follows. She was the third of four sisters, all of whom were healthy. Her parents were healthy and had no morphogenetic abnormalities. Her 35
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Fig. 2. Hand of subject with TRP I shows brachymetacarpia and characteristic deviation of the proximal interphalangeal joints of the second, third, and fourth fingers. Fig. 1. Facial features characteristic of TRP 1. Note high hairline, widely spaced eyebrows that are thick medially, elongated philtrum, and thin upper lip.
paternal grandfather was prematurely bald, and her great grandmother and great aunt on her father's side had certain deformities of their ears but since they were dead these could not be defined more precisely. There were no abnormalities in her karyotype. Results of echography of the abdomen and general laboratory tests on blood and urine were normal. Radiologic studies revealed slightly delayed skeletal maturation, thoracico-lumbar kyphoscoliosis, cone-shaped epiphyses in the middle phalanges of the hands and feet with joint abnormalities but no exostoses (Fig. 6). There was established Perthes disease (avascular necrosis of the proximal femur) in the fight hip with shortening and flattening of the femoral neck (coxa plana) and enlargement of the head of the femur (coxa magna) with deformity of the acetabulum. On a panoramic radiograph there was lack of space in the apical area of the maxilla in the region of the premolars and canines and in the posterior areas for the eruption of the second and third molars (Fig. 7). These are characteristic features of maxillary hypoplasia along with agenesis of the left mandibular second premolar. A cephalometric study (Steiner's analysis) (Fig. 8) showed a class one skeletal relationship between the maxilla and the mandible (ANB angle
Fig. 3. Patient's teeth in centric occlusion show posterior crossbite and buccally displaced, partially erupted right and left maxillary canines.
2.2 degree) and obvious vertical growth of the face (mandibular plane, SN angle 40.8 degree). A comparison of these parameters with King and Frias3 is displayed in Table I. The soft tissue profile of the upper and lower lips maintained a harmonic relationship with Steiner's aesthetic line. On the basis of all these findings a diagnosis was made of Giedion's type I trichorhinophalangeal syndrome.
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Fig. 4. Occlusal view of maxilla shows malposition and crowding of incisors. Dental development in patient is delayed as shown by the retained deciduous canine and molar teeth and partial eruption of left maxillary first molar.
Fig. 5. Occlusal view of mandible shows malposition of incisors and retention of deciduous molars of deciduous molars.
DISCUSSION This is an unusual and perhaps underdiagnosed genetic skeletal dysplasia with defects in the growth of the tubular bones, the spinal column, or both. 1 The syndrome is the result of a single autosomal dominant gene. Because of the scanty information provided by the family tree in this case, it must be classified as sporadic within this family. Appropriate genetic counseling was given. It was thought to be very important to distinguish this case from Langer-Giedion syndrome (type II trichorhinophalangeal syndrome) on the basis of the clinical abnormalities involved. The absence of multiple exostoses and of acute mental retardation (although cases without this have been described) support a diagnosis of type I. 1 The gene responsible for both syndromes has not been identified, but it has been demonstrated that TRP I is due to a mosaic deletion of band [email protected]
The more severe TRP II is due to a larger deletion at the same locus (extending from 8q24.11 to 8q24.13).4,5 The oral changes in this type of genetic skeletal dysplasia have not been described very often but attention has been drawn to malocclusion, supernumerary teeth, 5 microdontal teeth with a high rate of caries 6,7 and hypodontia. 8 Other more severe cases in which micrognathia 9 or bilateral dysplasia of the mandibular condyles t° are described have largely been attributed to type II. Our case lends some support to the descriptions of certain changes in the size and development of the jaws, particularly hypoplasia of the maxilla, which is
Fig. 6. Radiographs of the hands show deviation of fingers at proximal interphalangeal joints, sclerotic, shortened, and cone-shaped epiphyses of middle and proximal phalanges in the second, third, and fourth fingers.
responsible for the crossed bite posteriorly and the dental crowding. The predominant feature of the aforementioned cephalometric recordings is a posterior rotational pattern of growth of the mandible; this underlies the lengthening of the face, which is an integral part of the syndrome. The gonial angle of the mandible is more obtuse than normal as has been recorded by other clinicians. 3 The vertical growth pattern is demonstrated by the increased value of the mandibular plane-SN angle and gonial angle as reported by King and Frias. 3 Otherwise, there is no evidence of significant closing of the Na-S-Ar angle, but there is evidence of closing of the S-Ar-Go angle. These findings may represent some
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Fig. 7. Panoramic radiography shows crowding in apical area of maxilla, agenesis of left second premolar and signs of mandibular hypoplasia. l a n e I. Measurement of vertial dysplasia of jaw morphology and position compared with King and Frias. 3
Fig. 8. Cephalometic tracing of lateral cephalometric radiograph with Steiner's analysis shows a class I skeletal relationship between maxilla and mandible (ANB angle 2.2 degree; normal range 2 _+ 1 degree) and growth of the face (mandibular plane-SN angle 40.8 degree, normal range 32 _+ 2 degree). Soft tissue profile is harmonious with Steiner's aesthetic line.
overlapping between type I and type II syndromes as has been recorded with other clinical features by other clinicians.5 This patient's dentition could not be regarded as
King and Frias
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N N N I D I I
N N N I N (128 degrees) I (143 degrees) I
Total face height S-Go/Na-Me Upper face height Se-PNS/Na-ANS Lower face height Ar-Go/ANS/Me Angularmeasurements S-Na-A S-Na-B A-Na-B GoGn-SNa Na-S-Ar S-Ar-Go Ar-Go-Gn i-1
D1, Increased;D, decreased;N, normal. Cephalomelriclandmarks:S, sella;Go, gonion;Na, nasion;Me, menton;Se, ethrnoidregistrationpoint;PNS, posteriornasalspine;ANS, anteriornasal spine;At, articulate;A, greatestdepressionsuperiorto upperincisor;B, greatest depressioninferiorto lowerincisor;Gn, gnathion;7, log axisof lower
incisor;L longaxisof upperincisor.
microdontal although there was agenesis of the left lower second premolar, which agrees with published findings of other clinicians.8 Although a considerable amount of caries and changes in the enamel have been described in similar cases, 7,u it was not possible to regard these findings as being different from the changes that could be found in any other patient (with
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no systemic disease and of the same social stratum and age as the patient in question).
2. Eilert RE. Bones and joints. In: Merenstein GB, Kaplan DW, Rosenbreg AA, editors. Silver, Kempe, Bruyn, and Fulginiti's handbook of pediatrics. 16th ed. Norwalk [CT]: Appleton & Lange; 1991. p. 792-823. 3. King GJ, Frias JL. A cephalometric study of the craniofacial skeleton in trichorhinophalangeal syndrome. Am J Orthodont 1979;75:70-7. 4. BiJhler EM, Btihler UK, Beutler C, Fessler R. A final word on the trichorhinophalangeal syndromes. Clin Genet 1987;31: 273-5. 5. Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck. New York: Oxford University Press; 1994. 6. Dumic M, Ille J, Mikecin M, Cvitkovic M, Hitrec V, Potocki K. Triho-rino-falangalni sindrom. Lijec Vjesn 1993;115:163-5. 7. Braga D, Manganoni AM, Gavazzoni R, Pasolini G, De Panfills G. A case of trichorhinophalarlgeal syndrome, type I. Cutis 1994;53:92-4. 8. Downing A, Welbury RR. The tricho-rhino-phalangeaI syndrome: a case report. Int J Paediatr Dent 1992;2:35-40. 9. Bauermeister S, Letts M. The orthopaedic manifestations of the Langer-Giedion syndrome. Ofthop Rev 1992;21:31-5. 10. Mandoule R LeBalc'h T, Petrel R Doyon D. Syndrome trichorhino-phalangien. A propos de quatre cas decouverts chez l'adulte. Radiol 1984;65:85-8. 11. Tuzovic S, Fiebach BJ, Magnus L, Sauerbei HU. Das trichorhinophalangeale Syndrom. Bericht uber eine Familie mit 14 Merkmalstragern in 5 Generationen. Rontgenblatter 1982;35: 391-7.
CONCLUSIONS A case of trichorhinophalangeal s y n d r o m e Type I has been presented. M a n y genetic skeletal dysplasias have craniofacial manifestations, and practitioners should be aware of the clinical features involved in this particular condition. Cephalometric analysis should be an integral part of the pretreatment orthodontic/dental functional and aesthetic evaluation as it helps to delineate the full extent of the craniofacial malformation. In this case, the pred o m i n a n t feature demonstrated by cephalometric analysis was the posterior rotational pattern of growth of the m a n d i b l e underlying the long face associated with this syndrome. Orthodontic treatment was needed to correct the dental malocclusion, but orthopedic treatment was not indicated. Patients with suspected G i e d i o n ' s s y n d r o m e should be referred for evaluation of avascular necrosis of the proximal femur and other skeletal abnormalities, and patients' families should be referred for genetic counseling. REFERENCES 1. Behrman RE, Kliegman RM, editors. Nelson. Tratado de Pediatrfa. Madrid: McGraw-Hill-Interamericana de Espafia; 1992. p. 2110-2.
Reprint requests: Prof. Dr. G. Machuca Departamento de Medicina Bucal y Periodoncia Clinica Odontol6gica Universitaria Universidad de Sevilla Avda. Dr. Fedriani s/n, 41009 Sevilla Espafia
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