Klippel-Feil syndrome involves a congenital fusion (failure of segmentation) of one or more cervical motion segments, and the clinical triad of short neck, low hairline, and restriction of neck motion is seen in only about half of the patients. Most patients have associated congenital anomalies at the craniocervical junction (occiput-C2), the subaxial spine (below C2), or both (Fig. 672-2). A familial gene locus on the long arm of chromosome 8 has been identified. Abnormalities in other organ systems must be ruled out. Associated anomalies have been identified in the genitourininary system (30-40%; unilateral renal agenesis, duplicated collecting systems, horseshoe kidney), auditory system, heart, neural axis, and the musculoskeletal system (Sprengel deformity in one third, scoliosis). Congenital cervical fusions or anomalies are also commonly seen in patients with Goldenhar syndrome, Mohr syndrome, VACTERL syndrome (vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal and/or radial anomalies, limb defects), and fetal alcohol syndrome.

Figure 672-2 Clinical picture of a 5 yr old with Klippel-Feil syndrome. A, Note short neck and low hairline. Radiographs of the cervical spine (B, flexion; C, extension) demonstrate congenital fusion and evidence of spinal instability (arrow).

(From Drummond DS: Pediatric cervical instability. In Weisel SE, Boden SD, Wisnecki RI, editors: Seminars in spine surgery, Philadelphia, 1996, WB Saunders, pp 292–309.)

Characteristic physical findings include a low hairline and a short, webbed neck. Decreased cervical motion is often present, although the degree of restriction depends on both the location and the number of levels fused. Whereas a C1-C2 fusion restricts cervical rotation >50%, but an isolated fusion in the subaxial spine has negligible loss of motion. Patients are evaluated with posterior, anterior, lateral, and oblique views of the cervical spine. The characteristic finding is a congenital fusion of ≥2 vertebrae (failure of segmentation), and multiple vertebrae may be involved. Because congenital anomalies can exist in more than one region of the spine, radiographs of the thoracic and lumbosacral spine are routinely obtained. Approximately 75% of cases involve the upper 3 cervical vertebrae, and the most common level is C2-C3. Half of the patients will have involvement of <3 vertebrae. Flexion and extension radiograph are commonly used to rule out hypermobility of instability, and an MRI with or without flexion and extension is also commonly obtained.

Symptoms are more common in adults than in children or adolescents and include pain and/or neurologic dysfunction. Excessive segmental motion can become clinically evident as radiculopathy or myelopathy, and brainstem compression can also occur. Spinal stenosis can also result in pain and/or neurologic compression. Degenerative changes in the disks and/or facet joints are likely due to the altered mechanical stresses, and segmental hypermobility (or instability) usually develops at the mobile segments adjacent to fused segments. The risk increases with the number of fused segments. MRI studies have demonstrated coexisting abnormalities in 85% of patients, including degenerative changes (disc protrusion, osteophytes, stenosis) and neural anomalies (syringomyelia, Chiari I malformation, diastematomyelia). A recent study found that there is a decrease in vertebral body width in the fused segments (likely due to interruption of appositional bone growth) and that the space available for the spinal cord was actually increased at these levels. Surgical treatments usually involve either decompression (with or without fusion) for stenosis associated with neural encroachment, and spinal fusion for instability. Occasionally a progressive cervicothoracic scoliosis requires stabilization to prevent deformity.

Bibliography

Hensinger RN, Lang JE, MacEwen GD. Klippel-Feil syndrome: a constellation of associated anomalies. J Bone Joint Surg Am. 1974;56:1246-1253.

Pizzutillo PD, Woods M, Nicholson L, et al. Risk factors in Klippel-Feil syndrome. Spine. 1994;19:2110-2116.

Samartzis D, Kalluri P, Herman J, et al. The role of congenitally fused cervical segments upon the space available for the cord and associated symptoms in Klippel-Feil patients. Spine. 2008;33:1442-1450.

672.3 Cervical Anomalies and Instabilities

David A. Spiegel, John P. Dormans

Anomalies of the craniovertebral junction and/or the lower cervical spine may be seen in isolation or in association with other conditions such as genetic syndromes and skeletal dysplasias. Congenital anomalies can result from a mutation in the homeobox genes. Coexisting abnormalities in other organ systems (renal, cardiac, intraspinal) must be ruled out. The true incidence is unknown, because many of these anomalies remain asymptomatic and undiagnosed. A subset of these anomalies, whether symptomatic or asymptomatic, places the patient at risk of neurologic injury due to either cervical instability or spinal stenosis. There seems to be no difference between syndromic and nonsyndromic anomalies when considering symptoms, findings, or treatment. Cervical instabilities may be associated with certain congenital anomalies, or with a variety of other conditions predisposing to excessive laxity or mobility (connective tissue disorders, metabolic diseases). The host of cervical anomalies and instabilities are categorized in Table 672-2.

Table 672-2 CAUSES OF PEDIATRIC CERVICAL INSTABILITY

CONGENITAL

Vertebral (Bony Anomalies)

Cranio-occipital defects (occipital vertebrae, basilar impression, occipital dysplasias, condylar hypoplasia, occipitalized atlas)

Atlantoaxial defects (aplasia of atlas arch, aplasia of odontoid process)

Subaxial anomalies (failure of segmentation and/or fusion, spina bifida, spondylolisthesis)

Ligamentous or Combined Anomalies

Found at birth as an element of somatogenic aberration

Syndromic Disorders

Down syndrome

Klippel-Feil syndrome

22q11.2 deletion syndrome

Larsen syndrome

Marfan syndrome

Ehlers-Danlos syndrome

ACQUIRED

Trauma

Infection (pyogenic, granulomatous)

Tumor (including neurofibromatosis)

Inflammatory conditions (e.g., juvenile rheumatoid arthritis)

Osteochondrodysplasias (e.g., achondroplasia, diastrophic dysplasia, metatropic dysplasia, spondyloepiphyseal dysplasia)

Storage disorders (e.g., mucopolysaccharidoses)

Metabolic disorders (rickets)

Miscellaneous (including osteogenesis imperfecta, sequela of surgery)

Patients present with a variety of complaints include headache, neck pain, or neurologic symptoms such as radicular pain or weakness (myelopathy). The spectrum of symptoms or physical findings associated with craniovertebral anomalies also includes failure to thrive, dysphagia, sleep apnea, torticollis, or scoliosis. The pathophysiology of neurologic dysfunction can involve neural compression (spinal cord or brainstem), vascular compression (vertebrobasilar symptoms), and/or altered cerebrospinal fluid (CSF) dynamics.

Physical findings include a restriction in cervical range of motion in some anomalies, with or without neurologic abnormalities. In the upper cervical spine, flexion and extension take place at the occiput-C1 articulation, and rotation occurs at the atlantoaxial (C1-C2) joint. Neither possesses inherent osseous stability and instead depends on the integrity of the ligaments and joint capsules to constrain motion. In addition to a comprehensive history and physical examination, imaging studies are required in all patients who are symptomatic, as well as in patients with disease processes known to be associated with cervical anomalies or instabilities.

The radiographic evaluation begins with anteroposterior, lateral, and open mouth (odontoid) views, which may be supplemented by dynamic (flexion and extension lateral of cervical spine) radiographs in most cases. Dynamic radiographs are used to evaluate the degree of translation between vertebrae, most commonly C1 and C2, but also at the occipitocervical junction and in the subaxial spine. For a diagnosis of atlantoaxial instability, the atlanto-dens interval (ADI) should be <5 mm. Subaxial instability is suspected with translation of >3.5 mm and angulation of >11 degrees. Radiographic parameters for the diagnosis of occipitoatlantal instability are not well standardized. Computed tomography is used to define the bony anatomy of each anomaly, and MRI (including dynamic images in flexion and extension) is best for evaluating neurologic impingement.

Symptomatic treatment may be helpful, but patients with cervical instability and/or neurologic impingement often require surgical decompression and/or fusion. Fixed deformities with anterior compression require an anterior decompression prior to a posterior spinal fusion.

Pathologic conditions at the craniovertebral junction include occipitoatlantal fusion (occipitalization of the atlas), basilar impression and invagination, occipital vertebrae or condylar hypoplasia, and occipitoatlantal instability. These have been associated with conditions such as achondroplasia, diastrophic dysplasia, spondyloepiphyseal dysplasia, Morquio syndrome (mucopolysaccharidosis), and Larsen syndrome. Fusion between the occiput and C1 (occipitalization) is commonly associated with neurologic symptoms, often due to posterior compression at the level of the foramen magnum. Four morphologic types have been described, and patients with a coexisting fusion between C2 and C3 are at a higher risk (57%) of symptomatic atlantoaxial (C1-C2) instability. Basilar impression or invagination describes a situation in which the odontoid process migrates into the foramen magnum; it may be diagnosed in patients with rickets, skeletal dysplasias, osteogenesis imperfecta, and neurofibromatosis. Occipital condylar hypoplasia is a rare cause of upper cervical instability. Instability between the occiput and C1 may be associated with a variety of conditions associated with hyperlaxity (Down syndrome, Ehler-Danlos or other connective tissue disorders, post-traumatic) or with familial cervical dysplasia.

Atlantoaxial anomalies include hypoplasia (or aplasia) of the atlas, which often manifests with torticollis and may be associated with vertebral artery compression. Several variants have been reported. Hypoplasia (or aplasia) of the odontoid may be seen in Down syndrome, Morquio disease, and other skeletal dysplasias, and it is often associated with atlantoaxial instability. Familial cervical dysplasia is an autosomal dominant condition associated with a spectrum of anomalies involving C1 and C2. Os odontoideum represents a discontinuity in the midportion of the dens, and the upper portion of the dens moves along with the ring of C1, narrowing the space available for the spinal cord and often placing the spinal cord at risk of injury. The etiology of os odontoideum is still debated, and a traumatic origin is suspected in most cases, but one study found evidence for both post-traumatic and developmental variants.

The most common anomaly of the lower cervical spine (subaxial) is Klippel-Feil syndrome, and congenital fusions between vertebrae may also be seen in up to 50% of patients with fetal alcohol syndrome. Instabilities in this region are post-traumatic or develop from the abnormal stress distribution in the setting on congenital cervical fusions (Chapter 672.2).

Down Syndrome

Ligamentous hyperlaxity is a characteristic feature of Down syndrome and can result in hypermobility or instability at the occipitoatlantal or the atlantoaxial joints (Chapter 76). Hypermobility or instability at C1-C2 is found in up to 40% of children with Down syndrome, with occipitoatlantal hypermobility in up to 61%. These patients can also have coexisting congenital or developmental anomalies of the cervical spine such as occipitalization of the atlas, atlantal arch hypoplasia, basilar invagination, os odontoideum, and odontoid hypoplasia. All patients require screening by history and physical examination (at regular intervals) and at least a single series of cervical spinal radiographs, including a lateral view in flexion and extension. The goal is to establish whether patients have normal mobility (normal radiographic parameters), hypermobility (excessive translation but not expected to be at neurologic risk), or instability (high risk of neurologic deterioration). Although the specific recommendations vary between states, both clinical and radiographic screenings are required before participation in Special Olympics.

The clinical diagnosis of neurologic dysfunction may be challenging in this population of patients, and subtle findings such as decreased exercise tolerance and gait abnormalities (increased tripping or falling) may be the earliest signs of myelopathy. Although formal neurologic testing may be impossible, clonus and hyperreflexia may be identified on physical examination. Imaging studies are commonly used to diagnose and follow patients with hypermobility or instability. With regard to the atlantoaxial joint, the atlanto-dens interval (ADI) is measured as the space between the dens and the anterior ring of C1 (ADI) on lateral radiographs in neutral, flexion, and extension (Fig. 672-3). A normal ADI in children with Down syndrome is <4.5 mm. Hypermobility is diagnosed with an ADI between 4.5 and 10 mm, and an ADI >10 mm represents instability and carries a significant risk of neurologic injury. An MRI with flexion and extension, usually performed under supervision, helps to further evaluate instability and neurologic compression. Although hypermobility at the occipitoatlantal joint is present in >50% of children with Down syndrome, most patients do not develop instability or neurologic symptoms. The relationships at this articulation are difficult to measure reliably on plain radiographs, and a dynamic MRI can help to clarify the significance of any questionable radiographic findings. Involvement of the subaxial spine is less common and is typically encountered in the adult population of patients with Down syndrome. Degenerative changes and/or instability can result in pain, radiculopathy, and myelopathy.

Figure 672-3 Flexion (A) and extension (B) radiographs of a case of Down syndrome demonstrating atlanto-occipital hypermobility and subluxation. C, Instability and symptoms were relieved by an occipitoaxial arthrodesis.

Recommendations for surveillance of potential cervical instability in children with Down syndrome vary, and no formal guidelines have been established. An annual neurologic examination should be performed. It is reasonable to obtain plain radiographs of the cervical spine, including flexion-extension views, in all patients with Down syndrome. Flexion and extension radiographs are obtained every other year in those with a normal clinical exam. Those with abnormal findings or symptoms, or when neurologic compression is suspected, are sent for an MRI in flexion and extension. Patients with normal radiographs who are also neurologically normal may be allowed to participate in a full level of activities. Those in whom hypermobility is diagnosed should be restricted from contact sports and other high-risk activities that might increase the risk of trauma to the cervical spine. Only a small subset of patients with myelopathy or instability (ADI >10 mm) with impending neurologic injury are candidates for posterior atlantoaxial (or occipitocervical) fusion, because the risks of a major complication (death, neurologic dysfunction, nonunion of fusion) is significant in patients with Down syndrome.

22q11.2 Deletion Syndrome

The chromosome abnormality deletion of 22q11.2 is a common genetic syndrome and encompasses a wide spectrum of abnormalities including cardiac, palate, and immunologic anomalies. At least one developmental anomaly of the occiput or cervical spine is noted in all patients (Fig. 672-4). The occipital variations observed include platybasia and basilar impression. Atlas variations include dysmorphic shape, open posterior arch, and occipitalization, and axis variations include a dysmorphic dens. A range of cervical vertebral fusions is noted in these patients, most commonly at C2 and C3. Increased segmental motion is observed on dynamic imaging in >50% of patients, often at more than one level. All patients should have screening radiographs, and many require follow-up for the cervical spine.

Figure 672-4 Radiographs of the cervical spine in a child with 22q11.2 deletion syndrome showing evidence of platybasia, occipitocervical, and atlantoaxial instability. A, Neutral radiograph. B, Flexion. C, Extension.

(From Drummond DS: Pediatric cervical instability. In Weisel SE, Boden SD, Wisnecki RI, editors: Seminars in spine surgery, Philadelphia, 1996, WB Saunders, pp 292–309.)

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