Down Syndrome

Down syndrome (trisomy 21) is the most common inherited chromosomal disorder, with an estimated prevalence of 1 in 700 live births. Occipitoatlantal subluxation and atlantoaxial subluxation are the two most common cervical spine problems seen in patients with Down syndrome. Patients with symptomatic atlantoaxial or occipitocervical instability may suffer from neck pain, torticollis, myeloradiculopathy, spasticity, hyperreflexia, or clonus.^27,28

Occipitocervical instability is present to some degree in 40% to 50% of children with Down syndrome. To date, no studies have looked at the natural history of this problem. The normal occipitoatlantal joint is composed of reniform-shaped occipital condyles seated on cup-shaped articular facets supported by the capsular ligaments.²⁹ Analysis of the occipitocervical junction in children with Down syndrome demonstrated that the superior articular surface of C1 and the occipital condyle are flattened in these patients.³⁰ Surgical treatment is generally recommended in patients who have more than 10 mm of subluxation at the occipitoatlantal joint, although that decision must be made on an individual basis because of the low incidence of spinal cord injury in otherwise asymptomatic patients.^29–31

Atlantoaxial subluxation is related to either the excessive ligamentous laxity or the osseous abnormalities in patients with Down syndrome. Radiographic atlantoaxial instability, as determined by the atlantodental interval and measurements of spinal canal diameter, is present in 10% to 30% of patients with Down syndrome,^29,32–35 although only 1% of such patients have symptomatic C1-2 instability.^27,28 One study of pediatric patients with Down syndrome and symptomatic atlantoaxial instability found that more than 80% of patients had os odontoideum.²⁸

Suggestions have been made to screen children with Down syndrome for instability (Fig. 220-1).^29,34,36 Cervical radiographs, including flexion and extension views, should be performed initially at 3 years of age to assess for excessive motion. If radiographs are normal, they may be repeated every 5 years or at the time of consideration for participation in the Special Olympics.^29,34,36 For patients with abnormal results on screening studies (occipitocervical subluxation >10 mm, atlantodental interval >4.5 mm, or neural canal <12 mm), careful yearly follow-up is indicated. Surgical correction may be required if neurological signs and symptoms are present, if magnetic resonance imaging (MRI) shows spinal cord injury, if subluxation is progressive over time, or if an os odontoideum is present.²⁹

FIGURE 220-1 Down syndrome. A and B, Flexion and extension radiographs demonstrating greater than 5 mm of subluxation at the occipitoatlantal joint. C, Sagittal computed tomographic reconstruction demonstrating subluxation of the occipitoatlantal joint, as well as flattening of the superior articular surface of C1. D, Postoperative lateral radiograph showing reduction of the occipitoatlantal joint, occipitocervical instrumentation, and bony fusion.

Klippel-Feil Syndrome

First described in 1912,³⁷ the now-classic triad of a short neck, low hairline, and limited neck mobility is known as Klippel-Feil syndrome, although less than 50% of patients with congenital fusion of the cervical spine have all three signs. Patients without all three signs are considered to have Klippel-Feil variant.¹

The most common clinical finding in patients with KFS is a limited range of neck motion, particularly with lateral bending. Patients with extensive neck fusion and fusion of the craniovertebral junction are seen at an earlier age than those with subaxial fusion.⁴ Patients with C1-2 fusion are often first evaluated for pain in childhood, whereas those with lower cervical fusion are seen in the second or third decade of life or later when symptomatic junctional degeneration develops. Torticollis or neck webbing is present in just 20% of patients with KFS and is not specific to any particular cervical spine anomaly.^38,39 Neurological abnormalities seen in patients with KFS include brainstem dysfunction, myeloradiculopathy, and headaches.

Among several classification schemes for KFS developed over the years,^39–41 the most recent, presented by Tracy and colleagues, separates KFS into four classes and incorporates the mode of inheritance (Table 220-2).⁴⁰

TABLE 220-2 Klippel-Feil Syndrome Types

Imaging of the cervical spine is important for accurate diagnosis. Plain radiographs should be obtained to identify congenital fusions. Further imaging, including cervical spine flexion-extension radiographs, computed tomography (CT), or MRI, is done as indicated.

Achondroplasia

Achondroplasia, the most common form of dwarfism, is characterized by disproportionate shortening of the proximal ends of limbs relative to the trunk. It occurs in 1 in 26,000 to 28,000 births, with an estimated incidence of 0.03% to 0.05% of all live births.^42–44 It is inherited in autosomal dominant fashion, with 80% of cases attributed to spontaneous point mutations in the fibroblast growth factor receptor 3 gene located on chromosome 4.^42,44 The cause of achondroplasia is a decrease in the rate of endochondral bone formation with normal formation of membranous bone.

The predominant spinal condition in achondroplasia is compression, which can occur at the foramen magnum, subaxial cervical spine, or thoracolumbar spine (Fig. 220-2). The clinical features of patients with cervicomedullary compression secondary to stenosis of the foramen magnum include bulbar findings, myeloradiculopathy, hydrocephalus, and respiratory disorders. Symptoms of cervicomedullary compression in infants include excessive hypotonia, poor head control, feeding or sleep abnormalities, and apnea. The respiratory disturbances may have a multifactorial cause. Neurological findings may be difficult to detect in young patients because many children with achondroplasia are normally hypotonic during early infancy, although they often exhibit developmental delay in achieving motor milestones.⁴⁵ A small percentage of patients with stenosis of the foramen magnum have symptoms of cervicomedullary compression.^45,46 In a prospective evaluation of 53 infants with achondroplasia, more than 70% had foramen magnum stenosis, but less than 10% demonstrated clinical symptoms of cervicomedullary compression.⁴⁶

FIGURE 220-2 Achondroplasia. This 15-month-old achondroplastic dwarf had hyperreflexia and a weak right arm. A, Sagittal computed tomographic scan demonstrating a decreased anteroposterior diameter of the foramen magnum, a thick foramen magnum, and platybasia. B, Sagittal T2-weighted magnetic resonance image showing compression of the brainstem and upper cervical spinal cord with signal abnormality within the spinal cord parenchyma.

Sudden death as a catastrophic consequence of cervicomedullary compression has been reported in infants with achondroplasia.^46,47 Hecht and colleagues reported a 7.5% risk for sudden death within the first year of life and a 2.5% risk for sudden death between 1 and 4 years of age in children with achondroplasia.⁴⁷

Goldenhar’s Syndrome

Goldenhar’s syndrome (GS, oculoauriculovertebral dysplasia) is a clinically heterogeneous disorder characterized by hemifacial microsomia, epidermoid appendages, and spinal defects. Other abnormalities include craniofacial, gastrointestinal, cardiac, renal, and ophthalmic anomalies. GS occurs in 1 in 300,000 to 500,000 live births.

Spinal abnormalities associated with GS include vertebral hypoplasia, failure of segmentation, and failure of vertebral formation. Segmentation defects are more common in the cervical spine, whereas vertebral formation abnormalities more frequently occur in the thoracolumbar spine. In one series, 60% of children with GS had vertebral anomalies,⁴⁸ including block vertebrae (most often involving fusion of C3 and C4), unilateral thoracolumbar hemivertebrae, spina bifida occulta, butterfly vertebrae, and sacral agenesis. Many patients had abnormalities at multiple spinal levels.

Upper cervical spine anomalies may also be seen in association with GS. One group reported a 12% incidence of vertebral segmentation anomalies and occipitalization of the atlas.⁴⁸ Odontoid hypoplasia with atlantoaxial instability has also been reported.⁴⁹

Spondyloepiphysial Dysplasia

Spondyloepiphyseal dysplasia (SED) encompasses several disorders characterized by abnormal growth of the spinal vertebrae and epiphysis. Individuals with SED have short-trunk dwarfism with shortened proximal and middle aspects of the limbs but relatively normal-sized hands and feet.

The most common spinal abnormalities in children with SED are odontoid hypoplasia and ligamentous laxity. Spinal cord compression from atlantoaxial instability causes myelopathy in as many as 35% of children with SED. The myelopathy usually develops gradually and is manifested as delayed motor development, slowly progressive weakness, spasticity, sleep apnea, and other respiratory abnormalities. Atlantoaxial instability has been found to progress with age in SED. Those with spinal canal diameters smaller than 10 mm at the level of the axis are at significantly increased risk for spinal cord compression.^50,51

Morquio’s Syndrome

Mucopolysaccharidosis (MPS) type IV, or Morquio’s syndrome, is an autosomal recessive lysosomal storage disease that results from an inability to metabolize keratan sulfate, a glycosaminoglycan found predominantly in cartilage and the cornea.^52,53 Patients often appear normal at birth and have normal growth and development for the first 2 years of life until the underlying skeletal abnormalities become clinically apparent between 2 and 6 years of age. The incidence of MPS IV is 1 in 40,000 live births. Many patients survive to early adulthood, at which time they may succumb to the cardiopulmonary and neurological complications of the disorder.

The most common spinal abnormality is atlantoaxial subluxation with spinal cord compression.⁵⁴ Atlantoaxial subluxation has been identified in 42% to 90% of patients with Morquio’s syndrome.⁵⁵ Odontoid dysplasia, which may be manifested as hypoplasia, aplasia, or os odontoideum, is common in MPS IV.

Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a hereditary disorder caused by a defect in collagen production. The disease is characterized by osteopenia, fragile bones susceptible to fracture, short stature, and progressive skeletal deformity.⁵⁶ The most commonly used classification system for OI is the Sillence classification system.^57,58 Type I is mild with no long bone deformities, type II is lethal in the perinatal period with in utero fractures, type III is the most severe form in children who survive the perinatal period, and type IV is an undefined type with moderate bone deformities and variable short stature. Abnormalities at the craniovertebral junction are most commonly seen with type IV OI, with a prevalence ranging from rare to 25%.⁵⁷ Osteoporotic bones resulting in repetitive microfracture cause infolding of the occipital condyles with elevation of the clivus and posterior cranial fossa. This leads to upward migration of the cervical spine into the foramen magnum and symptomatic compression of the brainstem and lower cranial nerves (Fig. 220-3).⁵⁹

FIGURE 220-3 Osteogenesis imperfecta. A sagittal T2-weighted magnetic resonance image demonstrates platybasia, basilar impression, a Chiari malformation, and cervical syringomyelia.

Larsen’s Syndrome

Larsen’s syndrome is a rare congenital disorder of connective tissue.^60–69 The cervical spine is more commonly affected than the thoracic or lumbar spine. The most characteristic abnormalities include hypoplastic or flattened vertebral bodies, dysraphism, hemivertebrae, and wedged vertebrae.^63,64 Midcervical subluxations and kyphosis have been described in 12% of patients with Larsen’s syndrome.^64,70 With progression of the curve and increased instability, progressive myelopathy, segmental weakness, and even death may ensue as a result of respiratory insufficiency.^61–6365 Cervical kyphosis associated with anterior-posterior disconnection syndrome has also been described.^66,67,71

Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome, with an incidence of 1 in 3300 individuals.^72,73 Spinal lesions occurring in patients with NF1 include cervical kyphosis, spinal meningocele, dural ectasia, and paravertebral tumors.^74–78 Progressive cervical kyphosis may occur as a result of intrinsic ligamentous abnormality and abnormal bony architecture (Fig. 220-4). Cervical kyphosis can also occur after resection of soft tissue or extradural neurofibromas. The most common spine tumors in patients with NF1 are paraspinal neurofibromas.⁷⁵ Growth of these lesions may result in expansion of the foramina, enlargement of the spinal canal, and widening of the interpedicular distance, all of which may contribute to the development of instability and scoliosis. These lesions are often asymptomatic.

FIGURE 220-4 Neurofibromatosis. Extension (A), neutral (B), and flexion (C) lateral radiographs in a child with neurofibromatosis type 1 demonstrate a kyphotic deformity and cervical instability with the apex at C4. D, Neutral lateral radiograph after anterior C3-6 diskectomy, allograft fusion, and anterior plate fixation.

Reconstruction of the cervical spine to correct kyphotic abnormalities in patients with NF1 is typically done from the anterior direction first, with multilevel diskectomies, fusions, and instrumentation at the appropriate level, followed by posterior rib and cable arthrodesis if necessary.⁷⁹ Normal cervical alignment is the ultimate goal.

Kniest’s Syndrome

Kniest’s syndrome is a form of skeletal dysplasia characterized by typical facial features and large, stiff joints with contractures.⁸⁰ The syndrome is similar to metatrophic dysplasia because of the enlarged, stiff joints and similar to SED because of impaired spinal and epiphyseal growth. Patients with Kniest’s syndrome have soft cartilage, which leads to osteopenia of the spine and extremities.

All regions of the spine are affected in patients with Kniest’s syndrome, with the most common problems being atlantoaxial instability, odontoid hypoplasia, cervical hypoplasia and instability, and kyphoscoliosis of the thoracolumbar spine (Fig. 220-5).^81–84 Surgical challenges may be extreme because of poor bone quality and small patient size.

FIGURE 220-5 Kniest’s syndrome. A, Lateral radiograph of the cervical spine demonstrating a hypoplastic odontoid with occipitoatlantal subluxation. B, Coronal computed tomographic reconstruction revealing an incomplete C1 ring with lateral subluxation of the C1 lateral mass. C, Sagittal T2-weighted magnetic resonance image showing cervicomedullary compression.

Os Odontoideum

Although os odontoideum may be more of a posttraumatic than congenital disorder, its existence is significant and should be discussed in the context of congenital cervical lesions. Os odontoideum consists of dissociation between the body of C2 and the dens such that a disconnected ossicle takes the place of the intact odontoid process.⁸⁵

Patients with atlantoaxial instability from os odontoideum may be at risk for significant neurological injury. Most patients have neck pain and headaches from the instability, but instances of myelopathy, transient quadriparesis, and even sudden death after minor trauma have been reported as well.³² If instability is suspected, dynamic imaging with flexion and extension views should be obtained, augmented by CT or MRI. Posterior stabilization with rigid instrumentation techniques, without the use of a halo orthosis, has been shown to be extremely safe and effective for managing this disorder.^28,86–95

Occipitoatlantoaxial Level

Instability at the occipitoatlantal or atlantoaxial level may require surgical fusion. A wide variety of techniques are available to establish a solid arthrodesis at the desired level, including halo application, bone and wire fusions, implantation of contoured loops, and direct application of rigid screw and instrumentation constructs. Recent studies have shown a clear superiority of rigid screw and instrumentation techniques over older bone and wire techniques, and these techniques have been expanded and refined over time.

For occipitoatlantal instability without significant craniocervical deformity, an occiput-to-C2 fusion with screw fixation at C2 (either C1-2 transarticular, C2 pars, C2 translaminar, or a combination thereof) and rigid rod or loop instrumentation of the occiput, augmented with an iliac crest or rib autograft, is currently the preferred method. Children younger than 4 years or those with significant size-for-age constraints may be especially challenging, but studies have shown good long-term results with occipitocervical fusion in this population.

Atlantoaxial instability is typically managed with some type of direct instrumentation and fusion with autograft or allograft. Choices of direct screw instrumentation sites, with or without rod connections, include C1-2 transarticular, C1 lateral mass, C2 pars, and C2 translaminar. Extensive experience with these techniques in children has shown favorable results.

Special situations arise in patents with basilar invagination or basilar impression. Basilar invagination is characterized by encroachment of the foramen magnum by the upper cervical elements, usually the odontoid.^96–98 Basilar invagination may be associated with a variety of craniovertebral disorders, including occipitalization of the atlas, Chiari I malformation, syringomyelia, scoliosis, and KFS. Basilar impression has clinical characteristics similar to basilar invagination, but it is due to a bone-softening disorder such as OI.

Treatment of older children with basilar invagination or basilar impression usually begins with cranial traction and reduction. If the impression can be reduced, a posterior occipitocervical stabilization procedure can then be performed to maintain the reduction. If the invagination cannot be reduced or if the patient will not tolerate traction (common in younger children), transoral odontoid resection is performed, followed by posterior occipitocervical fusion. Patients with associated Chiari malformations will require suboccipital decompression, C1 laminectomy, and duraplasty during their posterior stabilization and fusion procedures.^96–102

Subaxial Cervical Spine Anomalies

The decision to perform operative stabilization in a child with a congenital cervical spine lesion below C2 is based on evidence of cervical spinal instability, neurological deficit caused by a compressive lesion, and progressive deformity. Radiographic evidence of cervical spine instability is not absolute, but the following serve as useful guidelines: vertebral body angulation greater than 15 degrees, vertebral body subluxation greater than 5 mm, or unilateral or bilateral locked facets.⁷⁹ Kyphotic angulation of more than 7 degrees probably represents significant ligamentous instability and predisposes the juvenile cervical spine to further kyphosis and instability.

Surgical stabilization for single-level cervical instability may be addressed from either an anterior or posterior direction. Typically, anterior cervical diskectomy and allograft fusion with rigid instrumentation or screw/rod instrumentation and fusion from a posterior direction will provide a solid arthrodesis. Multilevel cervical anomalies, including spondylolysis, high-grade spondylolisthesis, and significant kyphotic deformities, are uncommon but especially challenging from a surgical perspective.^103–109 Surgical reconstruction for significant cervical deformities may be performed in staged fashion, first from the anterior direction with multilevel diskectomies or corpectomies, followed by posterior arthrodesis if necessary.⁷⁹ Preoperative reduction with cervical traction may be useful in select, cooperative patients. Close attention must be paid to bone quality at surgery, and rigid internal fixation is important for achieving normal cervical alignment.