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CLINICAL CONFERENCE 1. Calvarium and Cranial Base In CLINICAL CONFERENCE 1. Calvarium and Cranial Base in Apert's Syndrome: An Autopsy Report SVEN KREIBORG, D.D.S. UWE PRYDSOE, D.D.S. ERIK DAHL, D.D.S. P. FOGH-ANDERSEN, M.D. A post-mortem examination of a 22-month-old boy with Apert's syndrome is reported. A linear coronal craniectomy performed at 11 months of age had fused completely in spite of the insertion of polyethylene film between the bony edges. Furthermore, pro- gressive synostosis of other cranial sutures was observed. Histological examination of the cranial base showed that the sphenofrontal suture was fused and that the entire cerebral surface, including the sella turcica, was characterized by bone resorption. The sphenooc- cipital synchondrosis was extremely wide and abnormally shaped, and the chondral growth activity seemed diminished. It was concluded that the patient exhibited primary as well as secondary growth disturbances in the calvarium and cranial base. The pre- mature synostosis of the coronal and sphenofrontal sutures and the anomaly of the sphenooccipital synchondrosis were interpreted as primary defects. The altered shape of the calvarium and the marked resorption and shortening of the cranial base were con- sidered secondary changes. Furthermore, the investigation indicated that the conven- tional linear coronal craniectomy cannot be expected to improve the craniofacial growth pattern in patients with Apert syndrome. Alternative surgical procedures were sug- gested. Introduction Apert's syndrome is characterized by premature synostosis of cranial sutures associated with syndactyly of the hands and feet (Apert, 1906). Clinically the patients exhibit brachycephaly, hypertelorism, exophthalmos, maxillary hypo- plasia, and mandibular prognathism (Park and Powers, 1920). The palate is high-arched with lateral swellings (Solomon, et al, 1973). Some of the foregoing features are age-dependent and are not always obvious in early childhood. Cleft palate or bifid uvula is found frequently (Peterson and Pruzansky, 1974). Virchow (1851) suggested that the altered shape of the calvarium in patients with premature synostosis of cranial sutures was the result of cessation of growth at right angles to the fused suture combined with compensatory growth in the open 'sutures. A similar interpretation was given by Bertelsen (1958). In roentgenological studies Seeger & Gabrielsen (1971) described combined premature synostosis of both the coronal and sphenofrontal sutures. Moss (1959, Supported by a grant from The National Institute of Dental Research, United States Public Health Service Research Grant DE-2858. - 296 CLINICAL CONFERENCE 297 1975) and Bennett (1967) suggested that the altered shape of the calvarium in patients with premature synostosis of cranial sutures was caused by a primary defect in the cranial base. In longitudinal roentgencephalometric studies of patients with Apert's syndrome, Kreiborg and Pruzansky (1971, 1972) showed that these patients exhibited growth disturbances in the calvarium, cranial base, and maxilla. The coronal sutures were fused in all cases resulting in a diminished antero-posterior development of the calvarium with no forward growth of the frontal bone. The anterior cranial fossa and the clivus were short, and the cranial base angle was flattened. The maxilla showed diminished forward growth, whereas the mandible followed a normal growth pattern. This resulted in a progressive deviation in the sagittal jaw relationship with development of a relative mandibular prognathism. To investigate the growth disturbances involved, the present post-mortem examination of a 22-month-old boy with Apert's syndrome was carried out in connection with the legal autopsy. The neurocranium was examined morpholog- ically and radiologically, and part of the cranial base was studied histologically. Case History The patient, a Danish male, was born five weeks before term weighing 3400 gm. The pregnancy was complicated by hydramniosis. The labour and delivery were uneventful. The mother was 24 and the father 26 years of age. This was their second child. The parents were nonconsanguineous, and there was no family history of congenital defects. Premature synostosis of cranial sutures, syndactyly of the hands and feet, and a cleft of the soft and part of the hard palate were diagnosed at birth. During his first ten months of life the patient had several upper respiratory tract infections FIGURE 1. The patient at 11 months of age. 298 Clinical Conference with fever and respiratory distress but otherwise thrived well. At eleven months of age (Figs. 1 and 2), he was hospitalized for a bilateral coronal craniectomy in order to prevent increased intracranial pressure. At that time, the neurocranium showed occipital flattening and increased width. The anterior and posterior fontanelles measured 4 cm. (AP). Skull radiographs revealed synostosis of the coronal sutures, a short anterior cranial fossa, frontal bossing, and shallow orbits. The head circumference was 49 cm. The palate showed the lateral swellings characteristic of the syndrome (Fig- ure 3). A chromosome study revealed a normal male karyotype. The craniectomy was extended to the open sutures in the temporal region and was made approximately 1.5 cm. wide. The bone edges were covered with FIGURE 2. Bony and soft tissue syndactyly of the hands and feet. FIGURE 3. Palatal configuration. CLINICAL CONFERENCE 299 polyethylene film to prevent bony fusion. The postoperative course was un- eventful. At the age of 22 months, the patient was admitted to the hospital for surgical closure of the cleft palate. At this time his height was 85 cm. (75th percentile) and his weight 13 kg. (just below the 50th percentile). The shape of the neurocranium was unaltered, but the head circumference had increased to 54 cm. Skull radiographs showed that the fontanelles were closed, whereas the sagittal, squamosal, and lambdoidal sutures were patent; the surgically created defects were visible. The anterior cranial fossa and the clivus were short. The sella turcica was enlarged, and the cranial base angle was flattened (n-s-ba = 137.0°). The maxilla was hypoplastic (n-s-ss = 71.5°) and the nasopharyngeal airway reduced. The bony orbits were shallow because of the forward position of the greater wings of the sphenoid and the maxillary hypoplasia. However, there was no clinical evidence of exophthalmos. The cleft palate was closed by a Wardill procedure. Postoperatively, the patient developed respiratory distress and died ten hours later from aspiration. Autopsy Report The post-mortem description will be limited to the craniofacial region. The sagittal and lambdoidal sutures could not be located, although they seemed patent on the skull radiographs. The fontanelles were closed, but there was a wide depression in the region of the metopic suture and anterior fontanelle. The polyethylene film inserted at the time of craniectomy was still present, but a complete fusion of the bony edges had taken place beneath the film (Figure 4). The skull was opened and the brain removed. After fixation, the brain weighed 1800 g. A frontal section of the cerebrum revealed a symmetrical but slightly dilated ventricular system and a septum pellucidum cyst measuring 3x2x1 cm. The cerebellum seemed normal. The histological examination revealed cerebral edema, subacute meningitis, and microgyri. ' The internal cranial base was extremely asymmetrical (Figure 4) in that the anterior, middle, and posterior cranial fossae were considerably reduced in size on the right side. V The sphenofrontal suture could not be identified. The sella turcica was enlarged and the clivus short. A tissue block (Figure 4) was removed from the cranial base by means of an oscillating saw. The tissue block was divided into three parts and fixation performed in Lillies fixative (Pearse, 1968). After fixation, the tissue blocks were demineralized in equal parts of 2% citric acid and 20% sodium citrate (pH = 6) for about two weeks. Sagittal sections of 8 to 104 were made and stained in to- luidin blue (pH = 7). Histolégical Findings The histological examination of the cranial base showed the sphenofrontal suture to be fused. The entire cerebral surface of the cranial base was characterized by varying degrees of bone resorption (Figure 5). The cribriform 300 Clinical Conference FIGURE 4. Internal surface of the cranial base. The demarcated area in the midline indicates the sampled area. The arrow indicates a bony union beneath the polyethylene film in the region of the previous craniectomy. plate exhibited the least pronounced resorption. The jugum sphenoidale and the sella turcica showed marked resorption except for the posterior clinoid process which consisted of cartilage. The cerebral surface of the occipital part of the clivus exhibited the most pronounced resorption, including the anterior border of the foramen magnum. The external surface of the cranial base was characterized by moderate bone apposition. The extremely wide and abnormally shaped spheno-occipital synchondrosis continued into the posterior clinoid process. The number of chondrocytes and hypertrophic cartilage cells was small indicating a diminished chondral growth activity. The width of the synchondrosis was larger in the cerebral part than in the pharyngeal part. Discussion The craniofacial anomalies found in this infant were consistent with previously reported clinical and roentgenological findings in patients with Apert's syndrome. CLINICAL CONFERENCE: 301 The diminished antero-posterior development of the calvarium
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