CERVICAL SPINE DISORDERS IN CHILDREN

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CERVICAL SPINE DISORDERS IN CHILDREN Martin J. Herman, MD, and Peter D. Pizzutillo, MD

Care of children with disorders of the cervical spine requires an understanding of the anatomic and biologic features particular to the developing pediatric spine. Congenital and developmental alterations further complicate evaluation and treatment. Knowledge of pediatric cervical spine disorders in Down syndrome, Klippel-Feil syndrome, osteochondrodysplasias, mucopolysaccharidoses, and posttraumatic instability is basic for orthopedic surgeons. Thorough patient evaluation and appropriate early management may prevent potential serious neurologic injury and other complications related to cervical spine pathology. ANAT0 MY

Segmentation of the cartilaginous anlage of the vertebral column occurs in weeks 6 to 8 in the growing embryo. The urogenital ridge and branchial arches are spatially and temporally related to the developing spine. This relationship explains, in part, the high association between congenital cervical spine anomalies and renal, facial, and ear malformations. Work in molecular embryology has identified homeobox genes.12 Sequential activation of this genetic grouping regulates embryonic differentiation and segmentation of the developing vertebral column. Mutations of these sequences may be responsible for some of the more common congenital cervical spine anomalies.2l

The pediatric cervical spine approaches the adult configuration by 8 years of age.' The atlas, axis, and subaxial spine each have unique patterns of ossification. The atlas (C1) is composed of three ossification centers at birth.14 There are individual centers for the body and for each of the neural arches (lateral masses). The anterior ring of C1 is unossified in children younger than l year and progressively ossifies and enlarges through age 6 to 9 years. The body of C1 fuses with the neural arches through the neurocentral synchondrosis by age 7 years. The posterior arch closes by age 3 years. The developing axis (C2) has four ossification centers: one for each neural arch, one for the body (occasionally two), and one for the dens.I5The basilar synchondrosis fuses by age 7 years in most children. A remnant of this fusion may persist as the subdental synchondrosis scar. A summit ossification center at the tip of the odontoid appears between age 3 and 6 years. This center fuses with the main portion of the odontoid by age 12 years in most children. Persistence of this ossification center can be a normal anatomic variant. The subaxial vertebral bodies (C3-C7) ossify from three centers: a body and two neural arches.' The posterior ring, formed by the two neural arches, fuses by 2 to 3 years of age. The neurocentral synchondrosesbetween the body and the neural arches anterolaterally fuse between 3 and 6 years of age. Incompletely ossified subaxial vertebral bodies may appear

From the Orthopaedic Center for Children, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania ORTHOPEDIC CLINICS OF NORTH AMERICA VOLUME 30 NUMBER 3 JULY 1999

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wedge-shaped in children younger than 7 years. The superior and inferior ring apophyses appear at puberty. These structures represent secondary ossification centers of the vertebral bodies and fuse by age 25 years in most adults. Other important differencesbetween the pediatric and adult cervical spine add to the complexity of caring for children with cervical spine pathology. Horizontal orientation of the cervical facet joints and relative laxity of the ligamentous and cartilaginous elements allow for increased cervical mobility in children younger than 8 years. This hypermobility may be accentuated in some connective tissue disorders and syndromes with associated ligamentous laxity. Congenital and developmental variations in cervical anatomy seen in HippelFeil syndrome, the skeletal dysplasias, and storage disorders also contribute to instability. Progressive instability of the cervical spine may be the cause of serious neurologic injury and even sudden death in children with these disorders.

A Figure 1. Rothman-Weisel method of measuring occipitoatlantal instability. The atlantal line is drawn connecting points 1 and 2. A line is drawn perpendicular to the atlantal line at the posterior margin of the anterior arch of the atlas. A second perpendicular line is drawn intersectingthe basion (point 3). The distance (x) between these lines should not vaty more than 1mm in flexion and extension. (Copley LA, Dormans JP: Pediatric Cervical Spine Disorders. J Am Acad Orthop Surg 6:204-214,1998; with permission.)

RADIOLOGIC EVALUATION

Radiologic evaluation of the child’s cervical spine should include anteroposterior, lateral, and open-mouth views on initial evaluation. Variability in the radiographic appearance of the pediatric cervical spine, especially in the child younger than 8 years, makes interpretation of imaging difficult at times for the orthopedic surgeon unaccustomed to evaluating the pediatric spine.3Misinterpretation of normal radiographic findings as pathology is common. Pseudosubluxation of C2 on C3 and C3 on C4 may appear as pathologic instability. Absent ossification of the anterior arch of C1 in infants may be interpreted as Cl-C2 instability. Persistence of the basilar synchondrosis of C2, loss of normal cervical lordosis, and variations in prevertebral soft tissue measurements may be normal findings in some children. Cervical instability at occiput-C1 and C1-C2 is best evaluated by flexion-extension lateral cervical spine radiographs. Occipitocervical instability is diagnosed when greater than 1 mm of translation is measured from the basion to the posterior margin of the anterior arch of C1 on flexion-extension views (Fig. l)?4 Anterior instabilityis detectableby a Powers ratio exceeding 1.0 (Fig. 2).lS Several other methods of measuring potential occipitocervicai instability have been described.

The atlas-dens interval (ADI) is commonly used to quantify the mobility of the atlantoaxial articulation (Fig. 3). The normal AD1 value for children is 4.5 mm or less, measured from the posterior margin of the anterior arch of C1 to the anterior margin of the dens.ll In the conditions with underlying potential C1-C2 instability, such as Down syndrome and the skeletal dysplasias, the AD1 may be increased as a baseline rnea~urernent?,’~ In such instances, measurement of the space available for the cord (SAC) may be more helpful in predicting pathologic instability. The SAC is measured from the posterior margin of the odontoid to the anterior margin of the posterior ring of C1. An absolute SAC less than 13 mm5 indicates insufficient space for the spinal cord and serves as an indirect measurement of encroachment on the neurologic structures (Fig. 4). Additional imaging studies may be helpful in evaluating the pediatric cervical spine. Tomography is useful for delineating the anatomy of congenital fusions and other cervical anomalies, particularly of the atlantoaxial region. Cineradiographic evaluation of the cervical spine is useful in identifying patterns of instability not readily appreciated with static flexion-extension views. Thin-cut axial computed tomography (CT)scanning with sagittal reconstruction is useful in defining bony anat-

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Figure 2. Method for determining Power‘s ratio. A line is drawn to the posterior margin of the atlas (A). Asecfrom the basion (8) ond line is drawn from the opisthion (0)to the anterior arch of the atlas (OA). The length of line B is divided by the length of line AO. A ratio greater than 1.O is diagnostic for anterior occipitoatlantal dislocation or instability.

omy. Magnetic resonance imaging (MRI) is indicated for evaluation of paracervical soft tissue and spinal cord pathology. MRI of the cervical spine in flexion and extension may detect encroachment on the spinal cord before permanent signal changes within the neural elements are seen, and thus may be the most sensitive test for identifying subtle neurologic injury associated with progressive pathologic instability. DOWN SYNDROME

Down syndrome (trisomy 20, a genetic disorder, occurs in 1 of 700 live births. Common

features include characteristic facies, congenital heart disease, ligamentous laxity, and mental retardation. Occipitocervicaland atlantoaxial instability are frequently seen in this group. The incidence of occipitocervical instability is reported to be as high as 61% in one series.” Atlantoaxial instability is seen in 9% to 22%of patients with Down ~ y n d r o m e . ’ ~ , ~ Progressive cervical instability and neurologic deficits are seen more commonly in boys than girls with Down syndrome. These children typically present with gait abnormalities, diminished exercise tolerance, and occasional neck pain. Physical examination may be significant only for mild extremity weakness and Space available for cord

Figure 3. Measurements for atlas-dens interval (ADI) and the space available for the cord (SAC) as determined on lateral cervical radiographs (see text).

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Figure 4. Extension (A) and flexion (8) lateral cervical radiographs of an adolescent boy with an 0s odontoideum and a progressive decrease in exercise tolerance. Note decrease in the SAC (arrow). Because the ossicle of the odontoid moves with the ring of C1, it is not possible to measure the ADI.

hyperreflexia, without findings about the cervical spine. An AD1 greater than 5 mm occurs in up to 15%of asymptomatic patient^.'^ MRI and neurophysiologic studies, such as somatosensory evoked potentials, in neck flexion and extension, may be indicated to detect subclinical neurologic compromise in patients with radiologic instability. CT scan may be helpful for defining possible associated anomalies in this patient group, including spina bifida of C1,os odontoideum, and persistent C2 synchondrosis.22 Careful correlation of history, physical examination, and diagnostic findings is recommended before prescribing treatment. Guidelines for surveillance of potential cervical instability in children with Down syndrome are unclear in the literature. The authors recommend cervical spine radiographs, including flexion-extension views, for children presenting with Down syndrome. Yearly physical examination with careful neurologic examination is advised. Cervical spine flexionextension views should be repeated at 3-year intervals. Avoidance of high cervical spine stress activities, such as tumbling and diving, is recommended for asymptomatic children with AD1 greater than 5 mm. Posterior cervical C1C2 fusion is recommended for AD1 exceeding 10 mm regardless of symptoms or for lesser

instability with neurologic sequelae. The authors recommend use of autologous iliac crest bone graft with or without internal fixation and postoperative halo immobilization. Complications of surgery, including nonunion, occur more frequently in this patient population (Fig. 5). Prophylactic fusion is not recommended. KLIPPEL-FEILSYNDROME

Klippel-Feil syndrome refers to a spectrum of congenital osseous anomalies of the cervical spine (Fig. 6).The triad of short neck, low posterior hairline, and limitations of cervical motion with associated congenital cervical fusions is seen in less than half of patients with this disorder. Commonly associated findings include congenital scoliosis (50% of patients), Sprengel's deformity, hearing impairments, synkinesia, and congenital heart disease.6Renal abnormalities occur in approximately one third of patients.I3Unilateral renal agenesis is the most common anomaly, with renal malrotation, horseshoe kidney, and ectopic kidney occurring less frequently. Children with Klippel-Feil syndrome present with a range of complaints, including issues of appearance, neck pain, changes in ex-

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with lower cervical involvement develop cervical spondylosis at more advanced ages. Yearly examination, including a thorough neurologic examination, is indicated for all patients. Yearly cervical flexion-extension radiographs are suggested for high-risk patients based on fusion location and pattern. Flexionextension views are recommended at 3-year intervals for all other patients with KlippelFeil syndrome regardless of symptoms. Symptomatic treatment of cervical complaints is indicated in patients with KlippelFeil syndrome without neurologic compromise. This treatment includes restriction of activities, use of cervical orthoses, and traction as needed. Posterior cervical fusion is recommended for progressive symptomaticsegmental instability or neurologic compromise. The preferred technique is onlay autologous iliac crest bone graft with postoperative halo immobilization. Prophylactic stabilization of patients with high-risk atterns of congenital fusions is not indicate8

Figure 5. Failed occipitocervical fusion in a patient with Down syndrome. Atlantoaxial instability persists.

OSTEOCHONDRODYSPLASIAS

The osteochondrodys lasias are a heterogeneous group of herita le disorders charac-

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ercise tolerance, and problems related to the associated anomalies. Decrease in cervicalmotion, especially lateral bend and rotation, is the most common physical finding. A thorough neurologic evaluation may reveal cranial nerve abnormalities, cervical radiculopathy or myelopathy. Radiographs of the cervical spine, including flexion and extension views, are indicated at presentation. Other recommended studies for all patients with the diagnosis of Klippel-Feil syndrome include radiographic views of the thoracic and lumbosacral spine, renal ultrasound, and audiologic testing. In the majority of Klippel-Feil syndrome patients, the congenital fusions and other anomalies occur in the upper cervical spine. Several authors have classified the specific anomalous patterns in an attempt to identlfy children at high risk for neurologic compromise. Hensinger and MacEwen7defined type I as C2-C3 fusion with occipitalization of the atlas. Type I1 is a long cervical fusion with an abnormal occipitocervicaljunction. Type I11 is two blocked vertebral segments with a single open interspace. Pizzutillo et all7described a functional classification. Patients with hypermobility of the upper cervical spine are at increased risk of neurologic injury, with presentation of neurologic " sesuelae in the teens or 20s. Patients

Figure 6. Lateral cervical spine radiograph of a 7-year-old boy with Klippel-Feil syndrome. Upper and lower cervical conaenital fusions are seen.

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terized by an intrinsic abnormality of bone and cartilage growth and remodeling. More than 120 different dysplasias have been identified? Patients with these disorders have a generalized disturbance of skeletal growth that affects the size and shape of the limbs and trunk and commonly manifests as disproportionateshort stature (dwarfism).Angular deformities of the extremities, premature degenerative joint disease, and spinal disorders, with potentially serious and life-threateningsequelae, are common clinical features of these varied dysplasias. Cervical instability occurs in a large percentage of patients. Thus, it is the responsibility of the orthopedic surgeon to recognize features of the skeletal dysplasias at initial presentation and to proceed with appropriate evaluation and diagnosis. Many of these patients require joint reconstructive procedures as adults. Preoperative evaluation of the cervical spine is mandatory before administration of general anesthesia.A thorough understanding of the natural history of these disorders is a prerequisite for the physician who provides long-term care for these patients. Identification of skeletal dysplasias may not be possible at birth. The diagnosis is often made when the disproportion of limbs and trunk is apparent with early growth. The physician should obtain a careful birth and family history and perform a thorough physical examination. A child in the 5th percentile or less for height within the first year of life must be assessed for a skeletal dysplasia or metabolic disorder. A skeletal survey is helpful in establishing a diagnosis. The appearance of the epiphyses and metaphyses of long bones and of the vertebral bodies provide useful information needed to narrow the differential diagnosis. Consultation with a geneticist is highly recommended to assist in establishing the precise diagnosis and in counseling the patient and family about all aspects of a particular dysplasia. Achondroplasia

Achondroplasia is the most common form of shortlimb disproportionate dwarfism. Inherited as an autosomal dominant trait, 80% of cases of achondroplasia are the result of a random new mutation. The primary effect of this mutation is abnormal endochondral bone formation. Characteristics of achondroplasia include an enlarged neurocranium with frontal bossing, a flattened nasal bridge with midface hypoplasia, and a prominent mandible.

Trunk length is normal. Extremity involvement is rhizomelic (proximal segments are more involved than distal segments) and angular deformities of the lower extremities are frequently seen. Thoracolumbar kyphosis is seen in infancy. An exaggerated lumbar lordosis develops after walking age. Spinal stenosis, in the lumbar spine and less commonly in the foramen magnum, is responsible for the most frequent and serious complications associated with achondroplasia. Stenosis of the foramen magnum may present with sleep apnea or sudden death in the infant and young child with achondroplasia.16 Dimished cross-sectional area of the foramen magnum encroaches on$he brain stem.” A CT scan is useful in defining the anatomy of the upper cervical spine. MRI, in conjunction with somatosensory evoked potentials, best defines brain stem and spinal cord abnormalities. Positioning of the head and neck in relative hyperextension, especially during sleep, and apnea monitoring are recommended in infants with achondroplasia. Foramen magnum decompression is performed for repeated apneic episodes or evidence of neurologic injury by diagnostic testing. Prophylactic decompression is not recommended. In contrast to most other types of the osteochondrodysplasias,atlantoaxial instability is uncommon in achondroplasia. Spondyloepiphyseal Dysplasia

Spondyloepiphyseal dysplasia (SED) is a term for a group of osteochondrodysplasias characterized by primary epiphyseal and vertebral involvement resulting in a short-trunk disproportionate dwarfism. SED congenita, SED tarda, spondylometaphyseal dysplasia, and spondyloepimetaphyseal dysplasia are subtypes of this grouping. These disorders have characteristic inheritance patterns and clinical and radiographic features that are often distinguishable by early childhood. Consultation with a geneticist is helpful in establishing the precise diagnosis. SED congenita (autosomal dominant) is commonly associated with disordersof the upper cervical spine. Recognized at birth, this short-trunk dwarfism is associated with pectus carinatum and barrel-chest deformities, thoracic scoliosis, exaggerated lumbar lordosis, lower extremity angular deformities, and hip flexion contractures. Radiographic features include platyspondyly, delayed vertebral body ossification, horizontal acetabular roofs

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with coxa vara, and epiphyseal irregularities in all long bones. Up to 40% of children with SED congenita develop atlantoaxial instab i l i t ~ .Odontoid ~ hypoplasia and 0s odontoideum are common features that predispose to this instability. Persistent hypotonia and delay in motor milestones may be the only early manifestations of neurologic compromise caused by this instability. Lateral flexion-extensionradiographs of the cervical spine are recommended on presentation for all children with SED. MRI in flexion and extension may detect encroachment on the upper cervical spinal cord. Surveillance for progressive upper cervical instability is performed in a manner similar to that suggested for children with Down’s syndrome (see earlier). Cineradiography may be particularly helpful in this patient group when plain radiographs in flexion and extension are difficult to interpret. Surgical stabilization is recommended prophylactically for instability greater than 5 mm and for instability with evidence of abnormal neurologic involvement clinically or by diagnostic studies. Instability may be detected in both flexion and extension. Atlantoaxial or occipitocervical posterior spinal fusion is recommended. The presence of an incomplete or hypoplastic ring of C1 necessitates inclusion of the occiput. The authors recommend use of autologous iliac crest bone graft without internal fixation and postoperative halo or Minerva immobilization. Care must be taken to avoid posterior overreduction if wiring techniques are used.

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inability to metabolize keratan sulfate characterizes this group. Children with Morquio’s syndrome manifest short-trunk dwarfism within the first 2 years of life. Coarse facial features, abnormal dentition, corneal clouding, ligamentous laxity, and joint stiffness develop in early childhood (Fig. 7). Radiographic features include oval-shaped vertebral bodies with anterior beaking; unossified femoral heads with proximal femoral valgus deformities; and broad, flat ilia. The diagnosis is made by urine screening for mucopolysaccharides and confirmed by serum testing for the specific sugar abnormalities. These children present to the orthopedic surgeon for evaluation of delays in motor development, joint stiffness, lower extremity deformities, and thoracolumbar kyphosis. Odontoid hypoplasia is common in children with Morquio‘s syndrome.9,’O Atlantoaxial instability with progressive myelopathy is one of

MUCOPOLYSACCHARIDOSES

At least 12 types of mucopolysaccharidoses (MPS) have been identified? These inherited genetic disorders are the manifestation of specific lysosomal enzyme deficiencies. As a consequence of these deficiencies, mucopolysaccharides (heparan sulfate, dermatan sulfate, keratan sulfate, and chondroitin sulfate) are incompletely metabolized within the lysozymes and accumulate in the brain, viscera, and joints throughout the body. Specific clinical features and the natural history of these disorders vary depending on the type and severity of the specific enzyme deficiency. These syndromes share some clinical and radiographic features. is the Morquio’s ‘yndrome (MPS type r, most COmmOn of these storage disorders;three different subtypes have been identified. The

Figure 7. Eight year old boy with Morquio syndrome. Note coarse hair and facial features, short trunk, pectus carinaturn, protuberantabdomen, and enlarged wrists and hands.

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the most disabling features of Morquio’s syndrome. Neurologic injury and sudden death are likely the result of spinal cord compromise from C1-C2 instability as well as extradural soft tissue hypertrophy anterior to the spinal cord in the upper cervical spine.2O Cervical spine radiographs, including flexion-extension lateral views, are recommended for all children presenting with Morquio’s syndrome as well as all other types of storage disorders (Fig. 8). Follow-up guidelines are similar to those described for Down’s syndrome patients (see earlier). Cervical stabilization is recommended for patients with atlantoaxial instability greater than 5 mm or with evidence of neurologic compromise. Posterior cervical Cl-C2 fusion with onlay iliac crest bone grafting and halo or Minerva immobilization is recommended. When occipitalization of C1 or a hypoplastic or incomplete ring of C1 is identified, occipitocervical posterior fusion is indicated. Stevens et alZoconcluded that occipitocervical fusion reduces the anterior soft tissue mass present at the level of the odontoid. Care must be taken to avoid posterior atlantoaxial over reduction if posterior wiring techniques are used. ODONTOID ANOMALIES Congenital anomalies of the odontoid are uncommon. Aplasia (complete absence of the

odontoid process), hypoplasia (partial absence of the odontoid process), and 0s odontoideum (free ossicle of smooth cortical bone in the normal superior position of the odontoid) may lead to progressive atlantoaxial instability.The cause of the most common type, 0s odontoideum, is unclear. In most cases, this lesion appears to be the result of a traumatic injury and not a true congenital anomaly or failure of fusion of the odontoid summit ossificationcenter (ossiculum ter~ninale).~ Patients with 0s odontoideum present with neck pain, loss of cervical motion, manifestations of upper cervical neurologic injury, and sudden death, generally in their teens. Flexionextension cervical spine radiographic views are helpful in defining the direction (anterior or posterior) and amount of instability. Upper cervical tomography and CT scan are helpful in defining the bony anatomy (Fig. 9). MRI evaluation in flexion and extension is used to assess potential spinal cord encroachment. Cervical stabilization is indicated for progressive instability with clinical or diagnostic evidence of cord encroachment or persistent neck pain. Posterior C1-C2 fusion with iliac crest bone graft and postoperative halo immobilization is recommended. Special care must be taken to avoid overreduction when using posterior wiring techniques in patients with atlantoaxial translation in flexion and extension. Occipitocervical fusion is indicated if

Figure 8. Lateral (A) and flexion (6) cervical radiographs of an 8-year-old boy with Morquio syndrome and neck pain. An enlarged cranium, odontoid hypoplasia, and atlantoaxial instability are seen. An occipitocervicalfusion with postoperativehalo immobilizationis recommended.

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Figure 9. Lateral cervical radiograph (A) and AP tomogram ( B ) of the upper cervical spine of a 5-year-old girl with neck pain. An 0s odontoideum is identified. Flexion-extensionlateral cervical spine radiographs are indicated to assess atlantoaxial stability.

a deficiency of the posterior arch of C1 exists concomitantly. Prophylactic stabilization of an asymptomatic 0s odontoideum is controversial. The risks and benefits of the procedure must be discussed in detail with the patient and family before proceeding.

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classification of osteochondrodysplasias. Am J Med Genet 44:223,1992 3. Cattell HS, Filtzer DL Pseudosubluxation and other normal variations in the cervical spine in children: A study of one hundred and sixty children. J Bone Joint Surg Am 471295-1309,1965 Hensinger RN, Hawkins RJ: 0 s odon4. Fielding JW, toideum. J Bone Joint Surg Am 62:376-383,1990 5. Hensinger RN: Osseous anomalies of the craniovertebral junction. Spine 11:323-330,1986 6. Hensinger RN, Lang JE, MacEwen G D Klippel-Feil syndrome. J Bone Joint Surg Am 561246-1253,1974 7. Hensinger RN, MacEwen GD: Congenital anomalies of the spine. In Rothman RH, Simeone FA (eds): The Spine. Philadelphia, WB Saunders, 1982, pp 188-315 8. Hopwood JJ, Morris CP: The mucopolysaccharidoses: Diagnosis,molecular genetics, and treatment.Mol Biol Med 7381,1990 9. Kopits SE: Orthopaedic complications of dwarfism. Clin Orthop 114:153-179,1976

10. Lipson SJ: Dysplasia of the odontoid process in Morquio’s syndrome causing quadriparesis. J Bone Joint Surg Am 59:87-92,1977 11. Locke GR, Gardner JI, Van Epps EF Normal values of atlas odontoid distribution in children. Am J Radiol 97135-140,1966 12. Manak JR, Scott MP: A class act Conservation of homeodomain protein functions. Development ( s u P P ~ )-71,1994 :~~ 13. Moore WB, Matthews TJ, Rabinowitz R Genitourinary anomalies associatead with Klippel-Feil syndrome. J Bone Joint Surg Am 57355-357,1975 14. Ogden JA: Radiology of postnatal skeletal develop ment: XI. The first cervical vertebra. Skeletal Radiol 1212-20,1984 15. Ogden J A Radiology of postnatal skeletal development MI.The second cervical vertebra. Skeletal Radiol 12:169-177, 1984 16. Pauli RM, Scott CI Jr, Wassman ER Jr, et a1 Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr 104:342-348, 1984 17. Pizzutillo PD, Woods M, Nicholson L, et al: Risk factors in Klippel-Feil syndrome. Spine 19:2110-2116, 1994 18. Powers B, Miller MD, Kramer RS, et a1 Traumatic anterior atlanto-occipital dislocation. Neurosurgery 412-17,1979 19. Pueschel SM, Scola FH:Atlantoaxial instability in individuals with Down syndrome: Epidemiologic, radiographic,and clinicalstudies. Pediatrics80:555-560, 1987 20. Stevens JM, Kendall BE, Crockard HA: The odontoid process in Morquio-Brailsforddisease: The effects of occiptocervical fusion. J Bone Joint Surg Br 732351858,1991 21. Subramanian V, Meyer BI, Gruss P: Disruption of the murine homeobox gene Cdxl affects axial skeletal

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identification by altering the mesodermal expression domains of Hox genes. Cell 83641-653,1995 22. TredwellSJ, Newman DE, Lockith G: Instability of the upper cervical spine in Down syndrome. J Pediat Orthop 10:602-606,1990

23. Wang H, Rosenblum AE, Reid CS, et al: Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction. Radiology 164:515-519,1987 24. Weisel S, Rothman RH:Occipito-atlantal hypermobility. Spine 4187-191,1979

Address reprint requests to Peter P. Pizzutillo, MD Orthopaedic Center for Children St. Christopher’s Hospital for Children Erie Avenue at Front Street Philadelphia, PA 19134