American Journal of Medical Genetics 43:704-708 (1992)
Cervical Spine in the Apert Syndrome Sven Kreiborg, Mason Barr, Jr., and M. Michael Cohen, Jr. Department of Pediatric Dentistry, The Royal Dental College, Copenhagen, Denmark (S.K.); Department of Pediatrics, Pathology, and Obstetrics, University of Michigan, Ann Arbor (M.B. J r J ; Department of Oral Biology, Faculty of Dentistry, and Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada (M.M.C. Jr.) Radiographs of the cervical spine-in many cases longitudinal-were available for study in 68cases of Apert syndrome. Autopsy material was available in one of these cases, and a 3-dimensionalreconstruction from a CT scan was also studied in one case. Variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Ossification may not always be evident in some early radiographs. However, early radiographic signs of impending fusion may be irregularity in vertical orientation of the vertebral bodies and narrowing of the involved intervertebral spaces. Cervical fusions occurred in 68%, single fusions being found in 37%, and multiple fusions in 31%.c&6 fusion was most common, alone or in combination with other fusions. In contrast, cervical fusions are known to occur in 25% of Crouzon patients, most commonly involving C2-C3only. It appears that when fusions are present, Cs c6 involvement in the Apert syndrome and CzC3involvement in the Crouzon syndrome separate the 2 conditions in most cases. Because cervical anomalies may complicate an already compromised airway in any form of acrocephalosyndactyly, it is imperative to initiate radiographic study of the cervical spine before undertaking anesthesia for surgery.
previously [Cohen and Kreiborg, 19911. In this study, we analyze the cervical spine for fusions in the Apert syndrome and compare the results with those observed in the Crouzon syndrome.
METHODS AND MATERIALS Lateral cephalograms that showed the cervical spine were available for study in 67 cases; autopsy material was available in one additional case. In most instances, the study was supplemented by frontal projections and conventional head films. Most patients were followed longitudinally so that changes over time, particularly during infancy and childhood, could be viewed. A 3dimensional reconstruction from a CT scan was also studied in one of the cases. Comparative data from the cervical spine in Crouzon syndrome were taken from Kreiborg [19811.
RESULTS Fused cervical vertebrae (Figs. 1 , 2 ) were observed in 46 of 68 cases (68%), single fusions being found in 25 (37%)and multiple fusions in 21 (31%).Specific cervical fusions are listed in Table I. c5-cefusion occurred most commonly. Isolated c5-c6fusion was found in 15 cases and multiple fusions involving C5-ce were present in another 15 cases. Thus, 65% of all our Apert cases with cervical fusions (n = 46)had a t least c5-Ce involvement. No Apert case had isolated Cz-C3involvement and only 2 0 1992 Wiley-Liss,Inc. cases had multiple fusions involving C&. The most complex fusions observed were C2-C3+ c4-c5-c6-c7and KEY WORDS: vertebral anomaly, cervical C&4-c&&. However, extensive fusions of this degree were very uncommon. anomaly, cervical fusion, APosteroanterior and lateral radiographs of a 3 l-week pert syndrome, Crouzon synApert fetus are shown in Figures 3 and 4.The lateral drome, acrocephalosyndacview shows fusion of the neural arches including C4-C5tYlY ce-c7.The posterioanterior view shows irregularity in vertical orientation of the vertebral bodies. Figure 5 demonstrates the histologic appearance of the cervical INTRODUCTION spine in sagittal section. The cartilaginous bodies of C,This work is part of a large study of 119 patients with c&&, appear undersegmented and neural arch futhe Apert syndrome. The sample has been described sion is evident in C,-C,-C5-C,-C7. In comparing the histologic section (Fig. 5) with the lateral radiograph (Fig. 4), Received May 20, 1991; revision received September 25, 1991. neural arch fusion is visible radiographically, but unAddress reprint requests to Dr. M. Michael Cohen, Jr., Dalhousie dersegmentation of the vertebral bodies is not; the former demonstrates ossification, whereas the latter are University, Halifax, Nova Scotia, Canada B3H 355. 0 1992 Wiley-Liss, Inc.
Cervical Fusions in Apert Syndrome
705
Fig. 1. Multiple cervical fusions. Note calcified stylohyoid ligament, another common feature of Apert syndrome.
mostly cartilaginous even though ossification centers are present.
DISCUSSION Fused cervical vertebrae have been described in the Apert syndrome by others: Schauerte and St-Aubin [19651(5of 9 cases); Hemmer et al. [1987] (5 of 7 cases); Sherk et al. [19821(4of 10 cases); and Rubin et al. [19721 (one case with multiple fusions of the cervical, thoracic, and lumbar spine). In our study, variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Radiographic evidence appears to be at least in part age dependent. Excluding the 31-week fetus (vide infra), the earliest fusion was evident at c5-c6in an 8-month-old infant. Three cases from the study of Schauerte and StAubin [1966] are instructive in this connection. In one instance, fusion of the proximal ends of the cervical spinous processes of C2-C3and c&6 found a t age 3 years 10 months was not observed earlier a t age 3 months. In another case, fusion of the cervical spinous processes at several levels at age 14 years was not observable in radiographs obtained shortly after birth. In a third case, C, and C, were discrete at age 8 112years, but were fused radiographically a t age 26 years. Even though ossification may not be observed in some early radiographs, if fusion is present, early signs may be irregularity of the vertebral column and narrowing of the involved intervertebral spaces. In the 31-week Apert fetus, cartilaginous undersegmentation of the vertebral bodies (Fig. 5) not yet visible as ossified fusion of the bodies but as irregularity of intervertebral spacing radiographically (Fig. 4) serves to make the point. The process of cartilaginous block fusion is similar to what is observed in the hands in Apert syndrome; failure of
Fig. 2. Multiple cervical fusions in Apert syndrome
separation of the cartilaginous models of the phalanges prenatally becomes evident with progressive ossification postnatally [Cohen, 1986; Schauerte and St-Aubin, 19661. Comparison with fused cervical vertebrae in Crouzon syndrome [Kreiborg, 1981; Kreiborg and Cohen, 19871 shows striking differences. The 1981 study shows a specific breakdown of various types (Tables11);fusions were
706
Kreiborg et al.
Fig. 3. Posteroanterior radiograph of cervical spine in a 31-week Apert fetus. Note neural arch fusions and irregularity in vertical orientation of vertebral bodies.
Fig. 4. Lateral radiograph ofcervical spine in 31-week Apert fetus. Note neural archfusionofC,-C,-C,C6G
observed in 15 of 61 cases (25%),lsingle fusions being found in 12 (20%),and multiple fusions in 3 (5%).C2-C3 involvement was extremely common, accounting for 14 of the 15 cases (Fig. 6). Only one case had isolated C5-C, fusion, and 3 cases had Cs-C, involvement combined with C,-C, fusion. In the study of 16 Crouzon patients by Hemmer et al. [1987], 3 had isolated C2-C3 fusion, 2 had isolated c5-c6fusion, and one had fusion extending from C, through C,. Because c5-c6fusion is so uncommon in Crouzon syndrome, we re-analyzed the 4 Crouzon patients with this Cervical spine anomalies of all kinds accounted for 30%, but this included one case of assimilation of the Atlas and 2 cases of occipitalization of C,.
finding in Kreiborg’s [19811 original sample. In every case, there was something unusual about the patient with C5-c,. Retrospectively we diagnosed one patient as having Jackson-Weiss syndrome. Another patient had agenesis of the corpus callosum, no calvarial digital markings, and short stature. The other 2 patients had limited extension of the fingers and elbows. One had involvement of the knees; the other had bony abnormalities (nonsyndactylous) of the hands and feet. Both had short stature. It is noteworthy that in the Crouzon sample, only 6 of 53 cases had limitation of extension of the elbows and 3 of these cases account for the unusual patients discussed here. The gene for the Crouzon syndrome remains unmapped. Therefore, it is not known whether the unusual
Cervical Fusions in Apert Syndrome
707
TABLE 11. Specific Cervical Fusions Found in 15 of 61 Patients with Crouzon Svndrome*
* From Kreiborg [198ll.
Fig. 6. C,-C, fusion in Crouzon syndrome [from Kreiborg and Cohen, 19871.
Fig. 5. Histologic parasagittal section of cervical spine in 31-week Apert fetus. Note undersegmentation of cartilaginous bodies (right) of C,-C,-C,-C,. Compare with intervertebral spacing between other bodies. Each vertebral body has an ossification center. Note fusion of neural arches (left)C&4-c&&. C,-c,-C,-C, have fused ossification centers and C3 is jointed to C4 by cartilaginous bridge.
fusions in other forms of acrocephalosyndactyly. Although the problem has yet t o be investigated systematically, the few known reports of vertebral fusions are summarized in Table 111. Other conditions with vertebral fusions of various kinds and of variable frequencies are listed in Table IV. It is important to recognize that any patient with Crouzon syndrome, Apert syndrome, or any other type of acrocephalosyndactyly should have radiographs of the cervical spine to assess any cervical anomalies that may be present before undergoing anesthesia for surgery. Cervical anomalies may compound the already problematic airwaf present in many of these patients because of their relatively inflexible necks. Especially before considering such patients for the modified prone position for cranial remodeling procedures [Park et al., 19851, basal CT scans as well as lateral flexion and extension cervical spine films should be taken to rule out possible craniovertebral abnormalities (particularly instability) that might result in injury of the cervicomedullary junction. If examinations are negative, patients can be safely selected for the modified prone position for cranial remodeling [Cohen, 19881.
cases represent heterogeneity, in which different genes may result in similar, slightly differing Crouzon phenotypes. Alternately, 3 of the 4 cases (omitting the retrospectively diagnosed Jackson-Weiss case) may possibly represent variable expressivity of a single Crouzon gene. In our literature review, we found 3 general estimates of vertebral fusions. Of 700 patients studied radiographically, Shands and Bundens [19561indicated that 2.3% had vertebral fusions, 1.1% had both vertebral fusions and other types of vertebral anomalies, and 0.43%had cervical fusions. Kreiborg [19811found cervical fusions in 0.7% of a general adult population (n= 153).In a study of 105 patients with cleft lip-palate, In the Apert syndrome, diminution of the nasopharyngeal Sandham [19861 noted cervical fusions in 2.9%. space and reduced patency of the posterior nasal choanae are Not much is known about the frequency of vertebral typically present during infancy and childhood.
708
Kreiborg et al. TABLE 111. Vertebral h s i o n s in Other Acrocephalosyndactylies Vertebral involvement
Condition Pfeiffer syndrome
c3-c4 c5-c6+L4-LS L-Ls c4-c&6
References Saldino et al. [19721
113 217 417
Cohen [19751 Hemmer et al. [19871
2 I7 115“ 1I1 1I1
Pantke et a1 [19751 Hemmer et al. [19871 Wells et al. [19901
Cervical block fusion Neural arch fusion Cs-c! Cervical facet fusion Block cervical and thoracic fusion
Saethre-Chotzen syndrome Acrocephalospondylosyndactyly a
No. affecteatotal no. 3 13 (same family)
Questionable fusion of anterior arch of atlas with base of skull in 2 other cases.
TABLE IV. Other Conditions With Vertebral Fusion* ~~
~
Condition Klippel-Feil anomaly Type 1 Type I1 Type I11 Type IV Wildervanck syndrome Fetal alcohol syndrome Oculoauriculovertebral spectrum Basal cell nevus syndrome Spondylothoracic dysplasia (autosomal dominant and recessive forms) Postaxial polydactyly-dental-vertebralsyndrome Binder “syndrome” MURCS association VATER association
Vertebral fusion Massive cervical fusion of upper cervical and thoracic vertebrae Cervical fusion of one or two interspaces Cervical and lower thoracic or lumbar fusions Cervical fusion and sacral agenesis Fusion involving cervical and sometimes thoracic vertebrae C2-C3fusion Cervical fusions Cervical or upper thoracic fusions Extensive vertebral fusions Variable vertebral fusions Cz-C3fusion Vertebral defects, especially from C5 to TI Fused cervical and thoracic vertebrae
* These vertebral fusions may only be present in some instances of a given disorder listed, e.g., fetal alcohol syndrome, Binder “syndrome,” and VATER association. Most of the information in this table is derived from Gorlin et al. [1990].For Binder “syndrome,”see Olow-Nordenram [1987] and for VATER association, see Weaver et al. [19861. Pantke HC, Gorlin RJ (1975):The Saethre-Chotzen syndrome. Birth Defects: Original Article Series 11(2):190-225. Cohen MM Jr (1975):An etiologic and nosologic overview of cranio- Park TS, Haworth CS, Jane JA, Bedford RB,Persing J A (1985):Modsynostosis syndromes. Birth Defects: Original Article Series, ified prone position for cranial remodeling procedure in children 11(2):137-189. with craniofacial dysmorphism: A technical note. Neurosurg 16:212-214. Cohen MM Jr (1986):“Craniosynostosis: Diagnosis, Evaluation, and Management.” New York Raven Press. Rubin MB, Pirozzi DJ, Heaton CL (1972):Acrocephalosyndactyly. Report of a case, with review of the literature. Am J Med 53:127-130. Cohen MM J r (1988):Craniosynostosis update 1987.Am J Med Genet Suppl 4:99-148. Saldino RM, Steinbach HI, Epstein CJ (1972):Familial acrocephalosyndactyly (Pfeiffer syndrome). An J Roentgen01 116:609-622. Cohen MM Jr, Kreiborg S (1991):Genetic and family study ofthe Apert syndrome. J Craniofacial Genet Develop Biol 11:7-17. Sandham A (1986):Cervical vertebral anomalies in cleft lip and palate. Cleft Palate J 23:206-214. Gorlin RJ, Cohen MM Jr, Levin LS (1990):“Syndromes ofthe Head and Neck.” New York: Oxford University Press. Schauerte EW, St-Aubin PM (1966):Progressive synosteosis in Apert’s syndrome (acrocephalosyndactyly)with a description of roentgenoHemmer KM, McAlister WH, Marsh J L (1987):Cervical spine anomagraphic changes in the feet. Am J Roentgen01 97:67-73. lies in the craniosynostosis syndromes. Cleft Palate J 24:328-333. Kreiborg S (1981): Crouzon syndrome: A clinical and roentgen- Shands AR Jr, Bundens WD (1956):Congenital deformities of the spine. An analysis of roentgenograms of 700 children. Bull Hosp cephalometric study. Scand J Plast Reconstr Surg [Suppll18:1-198. Joint Dis 17:llO-133. Kreiborg S, Cohen MM Jr, Aduss H (1986):Apert and Crouzon syndromes contrasted: Qualitative craniofacial X-ray findings. In D. Sherk HH, Whitake LA, Pasquariello PS (1982):Facial malformations and spinal anomalies. A predictable relationship. Spine 7:526-531. Marchac (ed):“Craniofacial Surgery.” Heidelberg: Springer-Verlag, pp 92-96. Weaver DD, Mapstone CL, Yu P-1 (1986):The VATER association. Analysis of 46 patients. Am J Dis Child 140:225-229. Olow-Nordenram M (1987):Maxillonasal dysplasia (Binder’s syndrome): A study of craniofacial morphology, associated malforma- Wells TR, Falk RE, Senac MO, Vachon L (1990):Acrocephalospondylotions and familial relations. Swedish Dent J Suppl 47:l-58. syndactyly-a possible new syndrome: Analysis of the vertebral and intervertebral components. Pediatr Pathol 10:117-131. Pantke OA, Cohen MM Jr, Witkop CJ Jr, Feingold M, Schaumann B,
REFERENCES
Cervical Spine in the Apert Syndrome Sven Kreiborg, Mason Barr, Jr., and M. Michael Cohen, Jr. Department of Pediatric Dentistry, The Royal Dental College, Copenhagen, Denmark (S.K.); Department of Pediatrics, Pathology, and Obstetrics, University of Michigan, Ann Arbor (M.B. J r J ; Department of Oral Biology, Faculty of Dentistry, and Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada (M.M.C. Jr.) Radiographs of the cervical spine-in many cases longitudinal-were available for study in 68cases of Apert syndrome. Autopsy material was available in one of these cases, and a 3-dimensionalreconstruction from a CT scan was also studied in one case. Variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Ossification may not always be evident in some early radiographs. However, early radiographic signs of impending fusion may be irregularity in vertical orientation of the vertebral bodies and narrowing of the involved intervertebral spaces. Cervical fusions occurred in 68%, single fusions being found in 37%, and multiple fusions in 31%.c&6 fusion was most common, alone or in combination with other fusions. In contrast, cervical fusions are known to occur in 25% of Crouzon patients, most commonly involving C2-C3only. It appears that when fusions are present, Cs c6 involvement in the Apert syndrome and CzC3involvement in the Crouzon syndrome separate the 2 conditions in most cases. Because cervical anomalies may complicate an already compromised airway in any form of acrocephalosyndactyly, it is imperative to initiate radiographic study of the cervical spine before undertaking anesthesia for surgery.
previously [Cohen and Kreiborg, 19911. In this study, we analyze the cervical spine for fusions in the Apert syndrome and compare the results with those observed in the Crouzon syndrome.
METHODS AND MATERIALS Lateral cephalograms that showed the cervical spine were available for study in 67 cases; autopsy material was available in one additional case. In most instances, the study was supplemented by frontal projections and conventional head films. Most patients were followed longitudinally so that changes over time, particularly during infancy and childhood, could be viewed. A 3dimensional reconstruction from a CT scan was also studied in one of the cases. Comparative data from the cervical spine in Crouzon syndrome were taken from Kreiborg [19811.
RESULTS Fused cervical vertebrae (Figs. 1 , 2 ) were observed in 46 of 68 cases (68%), single fusions being found in 25 (37%)and multiple fusions in 21 (31%).Specific cervical fusions are listed in Table I. c5-cefusion occurred most commonly. Isolated c5-c6fusion was found in 15 cases and multiple fusions involving C5-ce were present in another 15 cases. Thus, 65% of all our Apert cases with cervical fusions (n = 46)had a t least c5-Ce involvement. No Apert case had isolated Cz-C3involvement and only 2 0 1992 Wiley-Liss,Inc. cases had multiple fusions involving C&. The most complex fusions observed were C2-C3+ c4-c5-c6-c7and KEY WORDS: vertebral anomaly, cervical C&4-c&&. However, extensive fusions of this degree were very uncommon. anomaly, cervical fusion, APosteroanterior and lateral radiographs of a 3 l-week pert syndrome, Crouzon synApert fetus are shown in Figures 3 and 4.The lateral drome, acrocephalosyndacview shows fusion of the neural arches including C4-C5tYlY ce-c7.The posterioanterior view shows irregularity in vertical orientation of the vertebral bodies. Figure 5 demonstrates the histologic appearance of the cervical INTRODUCTION spine in sagittal section. The cartilaginous bodies of C,This work is part of a large study of 119 patients with c&&, appear undersegmented and neural arch futhe Apert syndrome. The sample has been described sion is evident in C,-C,-C5-C,-C7. In comparing the histologic section (Fig. 5) with the lateral radiograph (Fig. 4), Received May 20, 1991; revision received September 25, 1991. neural arch fusion is visible radiographically, but unAddress reprint requests to Dr. M. Michael Cohen, Jr., Dalhousie dersegmentation of the vertebral bodies is not; the former demonstrates ossification, whereas the latter are University, Halifax, Nova Scotia, Canada B3H 355. 0 1992 Wiley-Liss, Inc.
Cervical Fusions in Apert Syndrome
705
Fig. 1. Multiple cervical fusions. Note calcified stylohyoid ligament, another common feature of Apert syndrome.
mostly cartilaginous even though ossification centers are present.
DISCUSSION Fused cervical vertebrae have been described in the Apert syndrome by others: Schauerte and St-Aubin [19651(5of 9 cases); Hemmer et al. [1987] (5 of 7 cases); Sherk et al. [19821(4of 10 cases); and Rubin et al. [19721 (one case with multiple fusions of the cervical, thoracic, and lumbar spine). In our study, variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Radiographic evidence appears to be at least in part age dependent. Excluding the 31-week fetus (vide infra), the earliest fusion was evident at c5-c6in an 8-month-old infant. Three cases from the study of Schauerte and StAubin [1966] are instructive in this connection. In one instance, fusion of the proximal ends of the cervical spinous processes of C2-C3and c&6 found a t age 3 years 10 months was not observed earlier a t age 3 months. In another case, fusion of the cervical spinous processes at several levels at age 14 years was not observable in radiographs obtained shortly after birth. In a third case, C, and C, were discrete at age 8 112years, but were fused radiographically a t age 26 years. Even though ossification may not be observed in some early radiographs, if fusion is present, early signs may be irregularity of the vertebral column and narrowing of the involved intervertebral spaces. In the 31-week Apert fetus, cartilaginous undersegmentation of the vertebral bodies (Fig. 5) not yet visible as ossified fusion of the bodies but as irregularity of intervertebral spacing radiographically (Fig. 4) serves to make the point. The process of cartilaginous block fusion is similar to what is observed in the hands in Apert syndrome; failure of
Fig. 2. Multiple cervical fusions in Apert syndrome
separation of the cartilaginous models of the phalanges prenatally becomes evident with progressive ossification postnatally [Cohen, 1986; Schauerte and St-Aubin, 19661. Comparison with fused cervical vertebrae in Crouzon syndrome [Kreiborg, 1981; Kreiborg and Cohen, 19871 shows striking differences. The 1981 study shows a specific breakdown of various types (Tables11);fusions were
706
Kreiborg et al.
Fig. 3. Posteroanterior radiograph of cervical spine in a 31-week Apert fetus. Note neural arch fusions and irregularity in vertical orientation of vertebral bodies.
Fig. 4. Lateral radiograph ofcervical spine in 31-week Apert fetus. Note neural archfusionofC,-C,-C,C6G
observed in 15 of 61 cases (25%),lsingle fusions being found in 12 (20%),and multiple fusions in 3 (5%).C2-C3 involvement was extremely common, accounting for 14 of the 15 cases (Fig. 6). Only one case had isolated C5-C, fusion, and 3 cases had Cs-C, involvement combined with C,-C, fusion. In the study of 16 Crouzon patients by Hemmer et al. [1987], 3 had isolated C2-C3 fusion, 2 had isolated c5-c6fusion, and one had fusion extending from C, through C,. Because c5-c6fusion is so uncommon in Crouzon syndrome, we re-analyzed the 4 Crouzon patients with this Cervical spine anomalies of all kinds accounted for 30%, but this included one case of assimilation of the Atlas and 2 cases of occipitalization of C,.
finding in Kreiborg’s [19811 original sample. In every case, there was something unusual about the patient with C5-c,. Retrospectively we diagnosed one patient as having Jackson-Weiss syndrome. Another patient had agenesis of the corpus callosum, no calvarial digital markings, and short stature. The other 2 patients had limited extension of the fingers and elbows. One had involvement of the knees; the other had bony abnormalities (nonsyndactylous) of the hands and feet. Both had short stature. It is noteworthy that in the Crouzon sample, only 6 of 53 cases had limitation of extension of the elbows and 3 of these cases account for the unusual patients discussed here. The gene for the Crouzon syndrome remains unmapped. Therefore, it is not known whether the unusual
Cervical Fusions in Apert Syndrome
707
TABLE 11. Specific Cervical Fusions Found in 15 of 61 Patients with Crouzon Svndrome*
* From Kreiborg [198ll.
Fig. 6. C,-C, fusion in Crouzon syndrome [from Kreiborg and Cohen, 19871.
Fig. 5. Histologic parasagittal section of cervical spine in 31-week Apert fetus. Note undersegmentation of cartilaginous bodies (right) of C,-C,-C,-C,. Compare with intervertebral spacing between other bodies. Each vertebral body has an ossification center. Note fusion of neural arches (left)C&4-c&&. C,-c,-C,-C, have fused ossification centers and C3 is jointed to C4 by cartilaginous bridge.
fusions in other forms of acrocephalosyndactyly. Although the problem has yet t o be investigated systematically, the few known reports of vertebral fusions are summarized in Table 111. Other conditions with vertebral fusions of various kinds and of variable frequencies are listed in Table IV. It is important to recognize that any patient with Crouzon syndrome, Apert syndrome, or any other type of acrocephalosyndactyly should have radiographs of the cervical spine to assess any cervical anomalies that may be present before undergoing anesthesia for surgery. Cervical anomalies may compound the already problematic airwaf present in many of these patients because of their relatively inflexible necks. Especially before considering such patients for the modified prone position for cranial remodeling procedures [Park et al., 19851, basal CT scans as well as lateral flexion and extension cervical spine films should be taken to rule out possible craniovertebral abnormalities (particularly instability) that might result in injury of the cervicomedullary junction. If examinations are negative, patients can be safely selected for the modified prone position for cranial remodeling [Cohen, 19881.
cases represent heterogeneity, in which different genes may result in similar, slightly differing Crouzon phenotypes. Alternately, 3 of the 4 cases (omitting the retrospectively diagnosed Jackson-Weiss case) may possibly represent variable expressivity of a single Crouzon gene. In our literature review, we found 3 general estimates of vertebral fusions. Of 700 patients studied radiographically, Shands and Bundens [19561indicated that 2.3% had vertebral fusions, 1.1% had both vertebral fusions and other types of vertebral anomalies, and 0.43%had cervical fusions. Kreiborg [19811found cervical fusions in 0.7% of a general adult population (n= 153).In a study of 105 patients with cleft lip-palate, In the Apert syndrome, diminution of the nasopharyngeal Sandham [19861 noted cervical fusions in 2.9%. space and reduced patency of the posterior nasal choanae are Not much is known about the frequency of vertebral typically present during infancy and childhood.
708
Kreiborg et al. TABLE 111. Vertebral h s i o n s in Other Acrocephalosyndactylies Vertebral involvement
Condition Pfeiffer syndrome
c3-c4 c5-c6+L4-LS L-Ls c4-c&6
References Saldino et al. [19721
113 217 417
Cohen [19751 Hemmer et al. [19871
2 I7 115“ 1I1 1I1
Pantke et a1 [19751 Hemmer et al. [19871 Wells et al. [19901
Cervical block fusion Neural arch fusion Cs-c! Cervical facet fusion Block cervical and thoracic fusion
Saethre-Chotzen syndrome Acrocephalospondylosyndactyly a
No. affecteatotal no. 3 13 (same family)
Questionable fusion of anterior arch of atlas with base of skull in 2 other cases.
TABLE IV. Other Conditions With Vertebral Fusion* ~~
~
Condition Klippel-Feil anomaly Type 1 Type I1 Type I11 Type IV Wildervanck syndrome Fetal alcohol syndrome Oculoauriculovertebral spectrum Basal cell nevus syndrome Spondylothoracic dysplasia (autosomal dominant and recessive forms) Postaxial polydactyly-dental-vertebralsyndrome Binder “syndrome” MURCS association VATER association
Vertebral fusion Massive cervical fusion of upper cervical and thoracic vertebrae Cervical fusion of one or two interspaces Cervical and lower thoracic or lumbar fusions Cervical fusion and sacral agenesis Fusion involving cervical and sometimes thoracic vertebrae C2-C3fusion Cervical fusions Cervical or upper thoracic fusions Extensive vertebral fusions Variable vertebral fusions Cz-C3fusion Vertebral defects, especially from C5 to TI Fused cervical and thoracic vertebrae
* These vertebral fusions may only be present in some instances of a given disorder listed, e.g., fetal alcohol syndrome, Binder “syndrome,” and VATER association. Most of the information in this table is derived from Gorlin et al. [1990].For Binder “syndrome,”see Olow-Nordenram [1987] and for VATER association, see Weaver et al. [19861. Pantke HC, Gorlin RJ (1975):The Saethre-Chotzen syndrome. Birth Defects: Original Article Series 11(2):190-225. Cohen MM Jr (1975):An etiologic and nosologic overview of cranio- Park TS, Haworth CS, Jane JA, Bedford RB,Persing J A (1985):Modsynostosis syndromes. Birth Defects: Original Article Series, ified prone position for cranial remodeling procedure in children 11(2):137-189. with craniofacial dysmorphism: A technical note. Neurosurg 16:212-214. Cohen MM Jr (1986):“Craniosynostosis: Diagnosis, Evaluation, and Management.” New York Raven Press. Rubin MB, Pirozzi DJ, Heaton CL (1972):Acrocephalosyndactyly. Report of a case, with review of the literature. Am J Med 53:127-130. Cohen MM J r (1988):Craniosynostosis update 1987.Am J Med Genet Suppl 4:99-148. Saldino RM, Steinbach HI, Epstein CJ (1972):Familial acrocephalosyndactyly (Pfeiffer syndrome). An J Roentgen01 116:609-622. Cohen MM Jr, Kreiborg S (1991):Genetic and family study ofthe Apert syndrome. J Craniofacial Genet Develop Biol 11:7-17. Sandham A (1986):Cervical vertebral anomalies in cleft lip and palate. Cleft Palate J 23:206-214. Gorlin RJ, Cohen MM Jr, Levin LS (1990):“Syndromes ofthe Head and Neck.” New York: Oxford University Press. Schauerte EW, St-Aubin PM (1966):Progressive synosteosis in Apert’s syndrome (acrocephalosyndactyly)with a description of roentgenoHemmer KM, McAlister WH, Marsh J L (1987):Cervical spine anomagraphic changes in the feet. Am J Roentgen01 97:67-73. lies in the craniosynostosis syndromes. Cleft Palate J 24:328-333. Kreiborg S (1981): Crouzon syndrome: A clinical and roentgen- Shands AR Jr, Bundens WD (1956):Congenital deformities of the spine. An analysis of roentgenograms of 700 children. Bull Hosp cephalometric study. Scand J Plast Reconstr Surg [Suppll18:1-198. Joint Dis 17:llO-133. Kreiborg S, Cohen MM Jr, Aduss H (1986):Apert and Crouzon syndromes contrasted: Qualitative craniofacial X-ray findings. In D. Sherk HH, Whitake LA, Pasquariello PS (1982):Facial malformations and spinal anomalies. A predictable relationship. Spine 7:526-531. Marchac (ed):“Craniofacial Surgery.” Heidelberg: Springer-Verlag, pp 92-96. Weaver DD, Mapstone CL, Yu P-1 (1986):The VATER association. Analysis of 46 patients. Am J Dis Child 140:225-229. Olow-Nordenram M (1987):Maxillonasal dysplasia (Binder’s syndrome): A study of craniofacial morphology, associated malforma- Wells TR, Falk RE, Senac MO, Vachon L (1990):Acrocephalospondylotions and familial relations. Swedish Dent J Suppl 47:l-58. syndactyly-a possible new syndrome: Analysis of the vertebral and intervertebral components. Pediatr Pathol 10:117-131. Pantke OA, Cohen MM Jr, Witkop CJ Jr, Feingold M, Schaumann B,
REFERENCES
