Pediatr Radiol (2008) 38:892–897 DOI 10.1007/s00247-008-0866-1
CASE REPORT
Craniofacial and temporal bone CT findings in cleidocranial dysplasia Guido E. Gonzalez & Paul A. Caruso & Juan E. Small & Robert W. Jyung & Maria J. Troulis & Hugh D. Curtin
Received: 26 November 2007 / Revised: 13 March 2008 / Accepted: 28 March 2008 / Published online: 30 April 2008 # Springer-Verlag 2008
Abstract Cleidocranial dysplasia (CCD) is a multistructural polyostotic genetic disorder that results from mutation of the CBFA1 gene. Hearing loss is a frequent finding in CCD. We describe the CT craniofacial findings in CCD and provide a comprehensive discussion of the CT temporal bone findings in these patients. Keywords Cleidocranial dysplasia . Child
G. E. Gonzalez : J. E. Small Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA P. A. Caruso (*) : J. E. Small : H. D. Curtin Department of Radiology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, 243 Charles St., Boston, MA 02114, USA e-mail:
[email protected] R. W. Jyung Department of Otology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA, USA M. J. Troulis Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Present address: G. E. Gonzalez Departamento de Imágenes, Clínica Alemana de Santiago, Santiago, Chile
Introduction Cleidocranial dysplasia (CCD) is a rare autosomal-dominant skeletal dysplasia with characteristics secondary to defective intramembranous and endochondral ossification. The dysplasia is caused by heterozygous intragenic mutations of the human CBFA1 gene involved in osteoblast differentiation [1]. Diagnosis requires skeletal evaluation, as the disorder has a characteristic phenotype including delayed closure of the fontanelle, wormian bones, hypoplastic or absent clavicles, short stature and abnormal dentition. Of note, hearing loss is a frequent finding; it occurs in 33% of patients [2]. Case reports have described variable radiographic features of this malformation and the clinical otologic findings. As CCD can affect the temporal bone, important otologic and audiologic manifestations can result in acute and chronic ear diseases and all forms of hearing loss [3, 4]. We present a patient with CCD and conductive hearing loss with CT depiction of the spectrum of craniofacial and temporal bone abnormalities characteristic of this condition.
Case report A 7-year-old boy with the diagnosis of CCD was referred for evaluation of hearing loss. According to his mother, his hearing loss had worsened bilaterally and symmetrically during the last several years. He displayed a recent need to increase the volume of the television but seemed to follow conversations fairly well at home. He received preferential seating at school but was doing well. He had not had a trial of hearing aids or assistive listening devices. There was no history of vertigo, tinnitus, otalgia, or otorrhea. He had no history of recurrent otitis media or family history of
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otologic disease. The referring otolaryngologist had placed ventilation tubes a year prior without improvement in hearing. On examination, he was noted to have a broad forehead, hypertelorism, and a palpable anterior fontanelle. His cranial nerves were intact. Otoscopic examination revealed narrow external auditory canals (EAC) and ventilation tubes that were in place and patent. The tympanic membranes were otherwise intact with clear middle ear spaces. The Weber test was midline and the Rinne test showed bone conduction greater than air bilaterally. The rest of his head and neck examination was benign. His most recent audiogram confirmed a moderate, predominantly low-frequency conductive hearing loss on the left and a moderate to severe conductive loss on the right, also worse in the low frequencies. A noncontrast craniofacial CT scan performed with 3-D surface renderings and high-resolution images of the temporal bones demonstrated multiple craniofacial malformations. The skull had a brachycephalic configuration with a cranial index of 88 (cranial index defined as width of cranium divided by length of cranium, normal 75–80), wide forehead, and prominent bilateral temporoparietal bossing. There was a gaping anterior cranial defect resulting from delay in closure of the anterior fontanelle, and metopic and sagittal sutures (Fig. 1). The mastoid and sphenoid fontanelles were also open bilaterally. The foramen magnum appeared enlarged and elongated (Fig. 1). There was hypertelorism, a V-shape high-arched hard palate without cleft, choanal stenosis, hypoplastic zygomae and delayed union of the mandibular symphysis (Figs. 2 and 3). There were crowding of the teeth in the maxilla and delayed eruption of the permanent dentition (Figs. 2 and 3). There were multiple predominantly occipital wormian bones
(Fig. 3). The images of the brain revealed an incidental left parieto-occipital porencephaly. CT of the temporal bone demonstrated bilateral EAC stenosis (Fig. 4). The tympanic cavities appeared welldeveloped and aerated. The mastoid air cells were severely underdeveloped bilaterally. The semicanals of the tensor tympani muscles were laterally positioned and the eustachian tubes appeared wide (Figs. 4 and 5). The malleus and incus appeared normal in shape but rotated: the manubria of the mallei were anteriorly positioned. The stapes appeared coarse, abutted, and fused to the tympanic portion of the facial nerve and the retrotympanum along the pyramidal eminence, as seen in axial, sagittal, and oblique reformats (Fig. 5). The oval windows appeared normal. The mastoid portions of the facial nerves appeared foreshortened and anteriorly positioned, but the tympanic segments appeared normal. No inner ear dysplasia was seen. Images of the trunk and extremities were not obtained; however, hypoplasia of the clavicles had been previously documented radiographically.
Fig. 1 3-D CT surface renderings of the skull. a Frontal view demonstrates a wide forehead, hypertelorism, narrow orbits, and bitemporal and biparietal bossing (arrows). b Left lateral view with removal of the right calvaria shows delay in closure of both the sphenoid (S) and mastoid (M) fontanelles, multiple parieto-occipital
wormian bones (thin black arrows), hypoplastic zygoma with recessed lateral orbital walls (thick black arrows), and a shallow nasal root and obtuse nasofrontal angle (white arrow). c Axial CT image shows an elongated foramen magnum as well as crowding of teeth in the maxilla
Discussion Martin and Meckel first described CCD in the middle of the 18th century. In 1898 Marie and Sainton named the disorder “hereditary cleidocranial dysostosis” and emphasized the three hallmark clinical features of the disorder: hereditary transmission, aplasia or hypoplasia of the clavicles, and overdevelopment of the transverse diameter of the skull associated with delay in closure of the fontanelles [5]. Since then, more than 1,000 cases of CCD have been reported describing the different skeletal alterations that characterize the syndrome. Several prior reports
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Fig. 2 2-D CT of the face. a Coronal reformat shows the persistent patent anterior fontanelle (black arrows), the V-shape high-arched palate (white arrows), prominent dentoalveolus, and nonclosure of the mandibular symphysis. b Panoramic reformat shows supernumerary
teeth, crowded teeth in the maxilla (black arrows), and delayed incomplete eruption of the first permanent maxillary molars (white arrows). c Axial CT of the nasal cavity shows bilateral choanal stenosis: the right choana measures 5.5 mm (normal 11 mm)
Fig. 3 Axial CT. a Note crowded teeth within a prominent maxillary dentoalveolus (black arrows), bilateral patent mastoid fontanelles, and dysplastic mandibular rami (white arrows). b Note prominent under-
pneumatized mastoids (black arrows) and parieto-occipital wormian bones (white arrows)
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have been published regarding the value of plain film radiographs in the diagnosis. Our case demonstrates the utility of CT in the diagnosis and characterization of this disorder. CCD is an autosomal-dominant genetic disorder that affects bones of membranous and endochondral origin. The frequency of new spontaneous mutations has been estimated at 20–40% [5]. In 1997 Mundlos et al. [1] demonstrated that mutations involving the CBFA1 gene located on chromosome 6p21 are responsible for CCD. CBFA1 is a specific transcription factor that plays a key role in osteoblastic differentiation from periosteal stem cells in long bones, as well as in osteoblastic precursors that originate in membranous bones. Mutations in CBFA1 result in delayed closure of sutures and fontanelles. Mundlos et al. [1] suggest that CBFA1 also plays a role in chondrocytic differentiation, where it might take part in the signaling process between the periosteum and chondrocytes. The role of CBFA1 in both long and membranous bone development is reflected in the characteristic hypoplasia of the clavicles, which have both membranous and endochondral origin, and in the delay in closure of fontanelles and sutures, especially the anterior fontanelle and metopic suture, which can remain open for life. Secondary centers of ossification can occur and result in numerous wormian bones, more frequently seen in the lambdoid sutures [1]. Other classic cranial findings described in the literature include brachycephalic configuration of the cranium, prominent frontal and parietal bossing, and a small skull base [5]. The foramen magnum is typically enlarged and turned forward and downward. In our patient, CT clearly demonstrated delayed closure of multiple sutures and fontanelles, wormian bones, brachycephaly, biparietal bossing, and an elongated foramen magnum (Fig. 1).
The facial features of CCD are well described [5]. Patients have hypoplastic midface and sinuses, which make the clinical appearance of a short midface and relatively large mandible and broad nose. The palate is usually highly arched with a higher incidence of submucosal clefts. In our patient, CT demonstrated many of these characteristic facial features (Figs. 1 and 2). Apert syndrome might exhibit a midline calvarial defect, midface hypoplasia, brachycephaly, hypertelorism, and high-arched palate, but can be distinguished from CCD based on the hypoplastic clavicle in CCD and on the syndactyly and craniosynostosis found in Apert syndrome but not in CCD. The reported dental abnormalities include delayed eruption of both deciduous and permanent teeth, and supernumerary, impacted, and ectopic teeth [5, 6]. Although the formation and eruption of the deciduous teeth are normal, there is a delay in the root resorption, which causes the permanent dentition to be much delayed and can result in failure to erupt. In our patient, CT allowed panoramic reformats that summarized the dental abnormalities including persistent deciduous teeth, delay in eruption, and crowding of the dentition (Figs. 2 and 3). Mental development, work capacity, and lifespan in patients with CCD are usually normal [5]. Epilepsy and schizophrenia have been infrequently reported; varying degrees of mental retardation have been reported but are thought to be coincidental [5]. Structural CNS abnormalities are infrequent but are not considered to be defining characteristics of the syndrome. In our patient, CT demonstrated a left parietal malformation of cortical development, a porus, although the patient had no history of seizure or neurologic deficit. Patients might have hypoplasia or aplasia of the clavicles with hypermobility of the shoulders [5]. Other skeletal
Fig. 4 Axial CT. a Note moderate left external auditory canal stenosis. b, c Images show lateral position of the semicanal of the tensor tympani muscle (white arrow) and the manubrium of the
malleus anteriorly rotated abutting the anterior wall of the tympanic cavity (curved arrow). The sinus tympanum is noted for reference (T). The petrosquamosal suture is accentuated (black arrows)
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Fig. 5 Abnormalities of the stapes. a–c Coronal (a), oblique axial (b), and sagittal (c) reformats through the stapes suprastructure suggest fusion of the stapes to the facial canal along the retrotympanum that might represent ossification of the stapedius (black arrows) and
rotation of the long process of the incus into the horizontal plane (white arrow). A myringotomy tube is present (white arrowhead). d Axial CT image shows similar fusion of the stapes on the left
anomalies involve the scapulae, ribs, pelvis, spine, hands, and feet and are detailed in the literature. In our patient, hypoplasia of the clavicles was found. A wide variety of both anatomic and functional audiologic abnormalities have been described in patients with CCD, and hearing loss is a common complaint. Visosky et al. [2] studied nine patients with CCD and reported clinically relevant hearing loss in 33%. Eustachian tube dysfunction was present in 78%. They reviewed previous studies of otologic disorders in patients with CCD and found stenosis of the EAC to be the most frequent abnormality. Pou [7] described a patient with findings similar to ours. The author found severe stenosis of the right EAC and otoscopically documented a coarse, malpositioned stapes fused to the retrotympanum that was surgically removed. The surgical specimen shown in the
report by Pou appears congruent with the CT image of the stapes from our patient. Although partial volume averaging remains a potential limitation of our report, the multiplanar capabilities of multidetector CT in our patient allowed multiplanar reformats that support fusion of the stapes to the fallopian canal and retrotympanum (Fig. 5). In summary, we present a patient with CCD in whom CT depicted the spectrum of craniofacial abnormalities characteristic of this syndrome. It is important to appreciate temporal bone findings in this disorder, as aural and otologic pathology might be the presenting symptoms of the disease [3, 8] and the syndrome can cause acute and chronic ear diseases and all forms of hearing loss [3, 4]. Acknowledgement We thank Dr. Mark Volk for his support and assistance with this project.
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