Broad spectrum of skeletal malformation complex in patients with cleidocranial dysplasia syndrome: radiographic and tomographic study

Abstract

Purpose: Cleidocranial dysplasia is an autosomal dominant disorder characterized by defective ossification of the intramembraneous ossification (primarily the clavicles, cranium, and pelvis), and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. Spine deformities were of progressive nature and considered to be the major orthopedic abnormalities encountered in our practice in patients with cleidocranial dysplasia. We aimed to further delineate the underlying spine pathology and its etiological understanding. Extraspinal deformities were dealt with respectively.

Material and methods: In this paper, we describe 7 patients who were consistent with the phenotypic and the genotypic characterization of cleidocranial dysplasia. Reformatted computed tomography (CT) scans have been applied in several instances to further understand the underlying pathology of progressive spine tilting. Radiographs were sufficient to illustrate other skeletal malformations.

Results: Anatomical survey demonstrates that a broad spectrum of frequently unrecognized orthopedic aberrations were encountered. We believe that torticollis has evolved in connection with the persistence of synchondrosis of the skull base and the upper cervical spine and these are strongly correlated to the well-known pathology of posterior occipital synchondrosis. Similarly, scoliosis and kyphoscoliosis resulted from the pathologic aberration of the cartilaginous stage of disrupted embryological development. All our results are discussed for the first time. Coxa vara, patellar dysplasia, and genu valgum were observed as extraspinal deformities.

Conclusion: This paper includes for the first time the anatomical analysis of the malformation complex of the craniocervical and the entire spine in patients with cleidocranial dysplasia. Reformatted CT scan was the modality of choice. We were able to illustrate that the persistence of skull base and the cervical spine synchondrosis were correlated with the pathological mechanism of the posterior occipital synchondrosis. Therefore, injuries to the craniocervical region in these patients might lead to a wide range of dreadful complications, ranging from complete atlanto-occipital or atlanto-axial dislocation to nondisplaced occipital condyle avulsion fractures with the possibility of morbid and or mortal outcome. On the other hand, the persistence of a cartilaginous spine was the reason behind the progressive spine tilting. This pathological form can be considered as a notoriously unpredictable malformation complex. The value of presenting these patients is to demonsterate that the genotype is not a precise index to assess the severity and the natural history of the phenotype.

Keywords: CT scanning; cleidocranial dysplasia; orthopedic interventions; radiographs; spine and skeletal malformations.

Figure 1

Skull radiographs show brachycephalic skull with increase biparietal diameter, frontal bossing, wide spaced sutures, multiple sutural (wormian bones), and absent parietal bone ossification. The anterior fontanelle remains open, associated with posterior occipital synchondrosis. Closure of the sutures is markedly delayed, and the anterior fontanelle are markedly enlarged. Persistence of the cranial fontanelles, especially the bregmatic, with diastasis of the sutures and a membranous texture upon palpation of the papyraceous cranium are constant features in CCD.

Figure 2

The trunks in all our patients were characterized by the presence of complete aplasia of the clavicles and are associated with disappearance of the supraclavicular and infraclavicular fossae so that the neck seems to imperceptibly continue into the thorax. Winged scapulae, drooping shoulders with abnormal excessive mobility, allowing the shoulders to be adducted to the point where the deltoid areas touch each other in the region of the sternum (puppet shoulders) are shown.

Figure 3

Reformatted CT scan of the skull show increased biparietal diameter and frontal bossing, and the anterior fontanel remains open and markedly enlarged in an adult patient. There was defective ossification of the mandibular menti (symphysis). In addition, there was persistence of the line of the 2 pieces of the mandible (persistent synchondrosis). Prognathism was marked associated with defective development of the upper jaw.

Figure 4

Sagittal reformatted CT scan in a 15-year-old adult patient with cleidocranial dysplasia showed defective ossification of the sella turcica and the clivus. In addition, it showed that the entirety of the skull base and most of the sphenoid bone and the clivus are cartilaginous, while the remainder of the cranial vault underwent defective membranous ossification. The odontoid is hypoplastic, and there was agenesis of the anterior arch of the atlas. Also note the severe ossification defects of the anterior and the posterior fontanels respectively.

Figure 5

Coronal reformatted CT scan in a 9-year-old patient showed dentocentral synchondrosis of the axis associated with odontoid process dysplasia and persistence of infantile synchondrosis over the entire cervical vertebrae.

Figure 6

Reformatted coronal CT scan of the spine in a 17-year-old adult patient showed the massive pathologic aberration of the cartilaginous stage of development (defective primary ossification of the vertebral column) causing effectively the maldevelopment of extensive butterfly-like and hemivertebrae like malformation (defective vertebral ossification) along the entire spine with subsequent development of progressive scoliosis/kyphoscoliosis.

Figure 7

AP radiograph in a 12-year-old patient showed valgus osteotomy of the proximal femora to correct the coxa vara. LCP-Pediatric-Hip Plate has been applied bilaterally to correct the varus deformity and to rotate the proximal femoral physis from a vertical to horizontal position.

Figure 8

Hemiepiphysiodesis in a 9-year-old patient (temporary hemiepiphysiodesis with 8-plates via timed hemiepiphysiodesis) was performed.

Figure 9

AP radiograph of the pelvis in a 9-year-old patient with cleidocranial dysplasia. Note that the pelvis showed a combination of delayed ossification of the ischium and pubis. In addition, there was maldevelopment of the capital femoral epiphyses, and both were separated from the metaphyses with upward and medial inclination. Note the gap between the epiphyses and the irregular metaphyses respectively.

Figure 10

Lateral knees radiograph in a 9-year-old patient showed defective ossification of the patellae with subsequent development of patellar maltracking.