Citations

Background: Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear. Methods: Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software. Results: Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001). Conclusions: Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Background: Little is known about the detailed growth of the cranial fossae, even though they provide an important structural connection between the cranial vault and the facial skeleton. This study details the morphologic development of isolated cranial vault synostosis and associated syndromes on cranial fossa development. Methods: A total of 125 computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome associated with bicoronal synostosis, n = 24; Crouzon syndrome associated with bicoronal synostosis, n = 11; and controls, n = 54). Three-dimensional analyses were produced using Materialise software. Results: The regional anterior and middle cranial fossae volumes of nonsyndromic bicoronal synostosis are characterized by significant increases of 43 percent (p < 0.001) and 60 percent (p < 0.001), respectively, and normal posterior cranial fossa volume. The cranial fossae depths of nonsyndromic bicoronal synostosis were increased, by 37, 42, and 21 percent (all p < 0.001) for anterior, middle, and posterior cranial fossae, respectively, accompanying the shortened cranial fossae lengths. The volume and morphology of all cranial fossae in Apert syndrome nearly paralleled nonsyndromic bicoronal synostosis. However, Crouzon syndrome had reduced depths of cranial fossae, and more restricted fossa volumes than both Apert syndrome and nonsyndromic bicoronal synostosis. Conclusions: Cranial vault suture synostosis is likely to be more influential on cranial fossae development than other associated influences (genetic, morphologic) in Apert and Crouzon syndromes. Isolated Apert syndrome pathogenesis is associated with an elongation of the anterior cranial fossa length in infants, whereas in Crouzon syndrome, there is a tendency to reduce cranial fossa depth, suggesting individual adaptability in cranial fossae development related to vault synostosis.

Background: The association of isolated craniosynostosis and the influence of syndromic forms confound the understanding of craniofacial morphologic development. This study attempts to clarify the individual influences of isolated bicoronal synostosis, Apert syndrome, and Crouzon syndromes on skull base morphology. Methods:: One hundred seventeen computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome with bicoronal synostosis, n = 25; Crouzon syndrome with bicoronal synostosis, n = 11; controls, n = 45). Cephalometric measurements were analyzed using Materialise software. Results: Nonsyndromic bicoronal synostosis patients developed a shortened cranial base length, with a significantly shortened distance between nasion and sella (p = 0.005). The cranial base angles of nonsyndromic bicoronal synostosis in both the cranial side (N-S-BA) and facial side (N-SO-BA) increased significantly, by 17.04 degrees (p < 0.001) and 11.75 degrees (p < 0.001), respectively. However, both the N-S-BA and N-SO-BA angles of Apert syndrome and Crouzon syndrome were narrowed more than that of nonsyndromic bicoronal synostosis [by 12.11 degrees (p < 0.001) and 12.44 degrees (p < 0.001), respectively, in Apert syndrome; and by 11.66 degrees (p = 0.007) and 13.71 degrees (p = 0.007), respectively, in Crouzon syndrome]. However, there is no statistically significant difference of these two angles between Apert syndrome and Crouzon syndrome, when they were only associated with bicoronal synostosis. Contrary to the relatively normal subcranial space of nonsyndromic bicoronal synostosis, both Apert and Crouzon syndromes developed a reduced subcranial space. Conclusions: Isolated bicoronal synostosis resulted in a flattened cranial base, whereas Apert syndrome and Crouzon syndrome developed a normal cranial base angle when only associated with bicoronal synostosis. The syndromic skulls had additional significantly reduced subcranial space.

Background: Apert syndrome causes normal or enlarged intracranial volume overall as patients grow. This study aimed to trace the segmental anterior, middle, and posterior cranial fossae volume and structural morphology in these patients, to help discern a more focused and individualized surgical treatment plan for patients with Apert syndrome. Methods: This study included 82 preoperative computed tomographic scans (Apert, n = 32; control, n = 50) divided into five age-related subgroups. The scans were measured using image processing and three-dimensional modeling software. Results: The middle cranial fossa volume was increased and was the earliest change noted. It was increased by 45 percent (p = 0.023) compared with controls before 6 months of age and remained increased into adulthood (161 percent, p = 0.016), with gradually increasing severity. The anterior and posterior cranial fossae volumes also increased, by 35 percent (p = 0.032) and 39 percent (p = 0.007), respectively. Increased depth of cranial fossae contributed most to the increase in volumes of patients with Apert syndrome, with correlation coefficients of 0.799, 0.908, and 0.888 for anterior, middle, and posterior cranial fossa, respectively. The intracranial volume was increased 12 percent (p = 0.098) across the entire test age range (0 to 26 years old), but only had statistical significance during the age range of 6 to 18 years (22 percent, p = 0.001). Conclusions: Malformation of the middle cranial fossa is an early, perhaps the initial, pivotal cranial morphologic change in Apert syndrome. Increased cranial fossae depth is an inherent characteristic of the maldevelopment. Normalization of cranial volume and circumference overall may not achieve a normal skull structure, as it does not correct regional craniocerebral disproportion.

Background: Patients with Crouzon syndrome develop various types of anatomic deformities due to different forms of craniosynostosis, yet they have similar craniofacial characteristics. However, exact homology is not evident. Different pathology then may be best treated by different forms of surgical technique. Therefore, precise classification of Crouzon syndrome, based on individual patterns of cranial suture involvement is needed. Methods: Ninety-five computed tomography (CT) scans (Crouzon, n = 33; control, n = 62) were included in this study. All the CT scans are divided into 4 types based on premature closure of sutures: class I = coronal and lambdoidal synostosis; class II = sagittal synostosis; class III = pansynostosis; and class IV = “Others.” The CT scan anatomy was measured by Materialise software. Results: The class III, pansynostosis, is the most prevalent (63.6%). The classes I, III, and IV of Crouzon have significantly shortened entire anteroposterior cranial base length, with the shortest base length in class III. The external cranial measurements in class I show primarily a decreased posterior facial skeleton, while the class III presented with holistic facial skeleton reduction. Class II has the least severe craniofacial malformations, while class III had the most severe. Conclusion: The morphology of patients with Crouzon syndrome is not identical in both cranial base and facial characteristics, especially when they associated with different subtypes of cranial suture synostosis. The classification of Crouzon syndrome proposed in this study, summarizes the differences among each subgroup of craniosynostosis suture involvement, which, theoretically, may ultimately influence both the timing and type of surgical intervention.

Background: Based on an established classification system of Apert syndrome subtypes, detailed regional morphology and volume analysis may be useful to provide additional clarification to individual Apert cranial structure characteristics, and treatment planning. Methods: Computed tomography scans of 32 unoperated Apert syndrome and 50 controls were included and subgrouped as: type I, bilateral coronal synostosis; type II, pansynostosis; type III, perpendicular combination synostosis. Three-dimensional analysis of craniometric points was used to define structural components using Materialise Mimics and 3-Matics software. Results: Occipitofrontal circumference of all subtypes of Apert syndrome patients is normal. Intracranial volumes of types I and II were normal, but type III was 20% greater than controls. Middle cranial fossa volume was increased in all 3 types, with the greatest increase in type II (86%). Type II developed a 69% increase in anterior cranial fossa volume, whereas type III had 39% greater posterior cranial fossa volume. Increased cranial fossa depth contributed most to above increased volume. The anteroposterior lengths of middle and posterior cranial fossae were reduced in type I (15% and 17%, respectively). However, only the anterior cranial fossa was significantly shortened in type III. Conclusions: Occipitofrontal circumference and overall intracranial volume is not always consistent in individual subunits of Apert syndrome. Detailed and segmental anterior, middle, and posterior cranial fossae volumes and morphology should be analyzed to see what impact this may have related to surgical planning.

Background From infancy to adulthood, the mandible develops increased ramus height, prominence of the chin, and laterally widened gonial angles. In Crouzon and Apert syndromes, both relative retrognathia and prognathic jaws have been reported. Growth is influenced by a variety of factors, including the growth and relative position of the skull base, functional coordination, and the spatial influence of the laryngopharynx. Thus, this study aimed to explore in detail the evolution of the mandible in both syndromes and its relationship with the entire facial structure and skull base. Methods One hundred twenty-three preoperative computed tomographic scans (Crouzon, n = 36; Apert, n = 33; control, n = 54) were included and divided into 5 age subgroups. Computed tomographic scans were measured using Materialise software. Cephalometrics relating to the mandible, facial structures, and cranial base were collected. Statistical analyses were performed using t test and statistical power analysis. Results In Crouzon syndrome, the angle between the cranial base and gnathion was increased prior to 6 months of age by 10.29 degrees (P < 0.001) and by adulthood to 11.95 degrees (P = 0.003) compared with normal. After 6 months of age, the distance between bilateral mandibular condylions (COR-COL) was narrower by 15% (P < 0.001) in Crouzon syndrome compared with control subjects. Before 6 months of age, Apert COR-COL decreased 16% (P < 0.001) compared with control subjects and 13% (P = 0.006) narrower than Crouzon. During 2 to 6 years of age, Apert mandibular ramus height caught up to, and became longer than, Crouzon by 12% (P = 0.011). The nasion-sella-articulare angle of the Apert skull was 5.04 degrees (P < 0.001) less than Crouzon overall. Conclusions In Crouzon syndrome, the changes of the spatial relationship of the mandible to the cranial base develop earlier than the mandibular shape deformity, whereas in Apert syndrome, the spatial and morphological changes are synchronous. The morphological changes of the mandible are disproportional in 3 directions, initially significant shortening of the mandibular width and length, and, subsequently, reduced height. Crouzon has more shortening in mandibular height compared with Apert, reflecting the more shortened posterior cranial base length. The narrowed angle between the mandible and the posterior cranial base in Apert skulls is consistent with the more limited nasopharyngeal and oropharyngeal airway space.