Cervical Vertebral Fusion/Cervical Spinal Fusion (arthrodesis) is a surgery that joins selected bones in the neck (cervical spine). There are different methods of doing a cervical spinal fusion: Bone can be taken from elsewhere in your body or obtained from a bone bank (a bone graft).
Klippel-Feil syndrome presents with an abnormal fusion of 2 or more bones in the cervical spine. This creates a characteristic appearance of a short neck with resulting facial asymmetry, low hairline, and limited neck mobility. This can lead to chronic headaches, a limited range of neck motion, and neck muscle pain. More importantly, it can also result in spinal stenosis, neurologic deficit, cervical spinal deformity, instability, and spinal stenosis. Patients can be poly-syndromic in their presentation as well. This activity reviews the evaluation of Klippel Feil syndrome and the role of the interprofessional team in managing this rare condition.
Klippel-Feil syndrome (KFS) is a complex condition presenting due to abnormal fusion of cervical vertebrae at C2 and C3, caused by a failure in the division or normal segmentation of the cervical spine vertebrae in the early fetal development. This condition leads to a characteristic appearance of a short neck, low hairline, facial asymmetry, and limited neck mobility. The anomalies can lead to chronic headaches, a limited range of neck motion, and neck muscle pain. More importantly, it can also result in spinal stenosis, neurologic deficit, cervical spinal deformity, instability, and spinal stenosis. Patients can be polysyndromic in their presentation, as well.[rx][rx][rx][rx]
Synonyms of Klippel-Feil Syndrome
- cervical vertebral fusion
- congenital cervical synostosis
- isolated Klippel-Feil syndrome
- Klippel-Feil anomaly
- KFS
Subdivisions of Klippel-Feil Syndrome
- Klippel-Feil syndrome, type I
- Klippel-Feil syndrome, type II
- Klippel-Feil syndrome, type III
Classification
In 1912, Maurice Klippel and Andre Feil independently provided the first descriptions of KFS. They described patients who had a short, webbed neck; decreased range of motion (ROM) in the cervical spine; and a low hairline. Feil subsequently classified the syndrome into 3 categories
- Type I — Fusion of C2 and C3 with a capitalization of the atlas. In 1953, further complications were later reported by McRae; flexion and extension are concentrated within the C1 and C2 vertebrae. As with aging, the odontoid process can become hypermobile, narrowing the space where the spinal cord and brain stem travel (spinal stenosis).
- Type II — Long fusion below C2 with an abnormal occipital-cervical junction. Similar to the C2-C3 fusion of McRae and could be viewed as a more elaborate variation. Flexion, extension, and rotation are all concentrated in the area of an abnormal odontoid process or poorly developed ring of C1 which cannot withstand the effects of aging.
- Type III – A single open interspace between two fused segments. Cervical spine motion is concentrated at single open articulation. This hypermobility may lead to instability or degenerative osteoarthritis. This pattern can be recognized as the cervical spine is often seen to be at an angle or hinge at this open segment.
A classification scheme for KFS was proposed in 1919 by Andre Feil, which accounted for cervical, thoracic, and lumbar spine malformations.[rx]
However, in 2006, Dino Samartzis and colleagues proposed three classification types that specifically addressed the cervical spine anomalies and their associated cervical spine-related symptoms, with additional elaboration on various time-dependent factors regarding this syndrome.[rx]
Causes of Klippel-Feil syndrome
The etiology of Klippel-Feil syndrome is not well known. Several studies have hypothesized that vascular disruption, global fetal insult, primary neural tube complications, or related genetic factors may carry implications in the development of KFS.[rx][rx][rx][rx] It can co-present with fetal alcohol syndrome, Goldenhar syndrome, as well as Sprengel deformity.[rx][rx][rx] In some families, mutations in the GDF6, GDF 3, and MEOX1 genes can cause Klippel-Feil syndrome and cane be inherited. GDF6 is involved in proper bone formation, while GDF3 is involved in bone development. MEOX1 gene creates the homeobox protein MOX1 that regulates the separation of vertebrae. GDF6 and GDF3 abnormalities are inherited in an autosomal dominant pattern, while MEOX1 mutations are autosomal recessive.[rx]
In most individuals with KFS, the condition appears to occur randomly for unknown reasons (sporadically). However, in other cases, familial patterns have been reported that indicate autosomal dominant or autosomal recessive inheritance. Most likely, KFS is multifactorial, which means that several different factors including genetic factors all play some causative role. In addition, different genetic defects can cause KFS (genetic herterogeneity) in different people.
Researchers have determined that some familial cases of KFS are associated with autosomal dominant transmission. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. For autosomal dominant inheritance the risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.
In 2008, researchers determined that some cases of autosomal dominant and sporadic KFS are caused by mutations of the GDF6 gene located on chromosome 8. The GDF6 gene produces a growth factor that is involved in the production and function of cartilage in the developing embryo. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted to bone. Researchers have determined that the growth factor produced by the GDF6 gene is essential to the proper function of the spinal discs found between the vertebrae. These discs provide flexibility and protection for the spinal cord. How mutations of the GDF6 gene contribute to the full spectrum of symptoms and physical findings associated with KFS is not yet known. Multiple synostosis 4 (SYNS4) is also associated with the mutation of GDF6.
Some cases of KFS have been reported that seem to suggest autosomal recessive inheritance. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.
The specific underlying causes and mechanisms that are associated with KFS are not fully understood. However, the condition appears to result from failure of the proper division (segmentation) of embryonic tissue that normally develops into vertebrae. As explained above, some cases are linked to mutations of the GDF6 gene. Other cases may be due to mutations in other genes or other causes. Further research is needed to learn more about the various underlying mechanisms that may be responsible for KFS and the exact roles genetic and other factors ultimately play in the development of the disorder.
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Healing osteomyelitis or discitis
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Previous fusion without instrumentation
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Juvenile idiopathic arthritis
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Juvenile rheumatoid arthritis can present with similar cervical spine anomalies, but a thorough workup and serological testing would facilitate differentiating from KFS easily
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Ankylosing spondylitis
Symptoms of Klippel-Feil syndrome
KFS is a rare skeletal condition in which there is abnormal union or fusion (congenital synostosis) of two or more bones (vertebrae) within the neck. The spinal column or backbone is made up of 33 irregularly-shaped bones known as vertebrae. These bones are divided into different categories. The first seven vertebrae, beginning at the base of the skull, are known as the cervical vertebrae. KFS primarily affects the cervical vertebrae.
KFS is usually diagnosed after birth. The most common signs of the disorder are restricted mobility of the neck and upper spine and a shortened neck with the appearance of a low hairline at the back of the head.
Associated abnormalities may include:[rx][rx][rx][rx]
- Scoliosis (sideways curvature of the spine)
- Spina bifida
- Problems with the kidneys and the ribs
- Cleft palate
- Dental problems (delayed dentition, cavities, missing teeth)
- Respiratory problems
- Heart defects
- Short stature
- Duane syndrome
- Srb’s anomaly
- Sprengel’s deformity
Two overlapping classification systems exist for KFS. The original classification of KFS subtypes (I, II, and III) described by Maurice Klippel and Andre Feil and one more recent updated classification of KFS Classes (KF1-4) as described by Clarke and colleagues [Clarke et al 1998]. The original classification differentiates individuals based on the degree of cervical fusion; KFS type I is characterized by an extensive fusion of vertebrae of the neck (cervical vertebrae) and the upper back (i.e., upper thoracic vertebrae); type II is characterized by fusion at one or two cervical or thoracic vertebrae; type III is characterized by a fusion of vertebrae of the neck as well as vertebrae of the upper or lower back (i.e., lower thoracic or lumbar vertebrae). In contrast, the classification described by Clarke et al differentiates individuals based on patterns of inheritance, common associated anomalies, and the axial level of the most anterior fusion. KF1 is the only class presenting with C1-2 fusion, the very short neck and recessive inheritance of type I, II, or III fusion patterns; KF2 is autosomal dominant with the most anterior fusion at C2-3 in association with type I, II, or III fusion patterns; KF3 is recessive or has reduced penetrance of isolated fusions between any of the cervical vertebrae except C1-2; KF4 includes cases of Wildervank and Duane syndrome.
The specific symptoms associated with KFS vary greatly from one person to another. Historically, KFS was associated with a classic triad of symptoms, specifically abnormally short neck, restricted movement of the head and neck, and a low hairline at the back of the head (posterior hairline). However, researchers have determined that these symptoms may define one class of KFS, which accounts for less than 50 percent of affected individuals.
In addition to the fusion of certain vertebrae, KFS can be associated with a wide variety of additional anomalies affecting many different organ systems of the body. The progression and severity of KFS can vary greatly depending upon the specific associated complications and the Class of KFS. Some cases may be mild; others may cause serious, life-long complications.
It is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms, and overall prognosis.
Approximately 30 percent of affected individuals have additional skeletal abnormalities, such as fusion of certain ribs or other rib defects; abnormal sideways curvature of the spine (scoliosis); or a condition known as Sprengel’s deformity. This condition is characterized by elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the shoulder blade. Also, in some individuals with KFS, a portion of the spinal cord may be exposed due to incomplete closure of certain vertebrae (spina bifida occulta). Associated findings may include the presence of a tuft of hair or dimple over the underlying abnormality and, in some cases, leg weakness, an inability to control urination (urinary incontinence), or other findings. As mentioned above, KFS type II may be associated with incomplete development of one-half of certain vertebrae (hemivertebrae) and fusion of the first vertebra of the neck (atlas) with the bone at the back of the skull (occipital bone).
Approximately 25 to 50 percent of individuals with KFS also have a hearing impairment. Such hearing loss may result from impaired transmission of sound from the outer or middle ear to the inner ear (conductive hearing loss); failed transmission of sound impulses from the inner ear to the brain (sensorineural hearing loss); or both (mixed hearing loss). Various eye (ocular) abnormalities may also be associated with KFS, such as deviation of one eye toward the other (cross-eye or convergent strabismus); involuntary, rapid eye movements (nystagmus); or absence or defects of ocular tissue (colobomas). In addition, some affected individuals may have other abnormalities of the head and facial (craniofacial) area including facial asymmetry, in which one side of the face appears dissimilar from another side, with one eye higher than the other. There may also be an abnormal twisting of the neck (torticollis), causing the head to be rotated into an abnormal position. According to some reports, approximately 17 percent of individuals with KFS also have incomplete closure of the roof of the mouth (cleft palate).
KFS may sometimes be associated with additional physical abnormalities. These may include structural malformations of the heart (congenital heart defects), particularly ventricular septal defects (VSDs). VSDs are characterized by the presence of an abnormal opening in the fibrous partition (septum) that separates the two lower chambers of the heart. Some individuals may also have kidney (renal) defects, such as underdevelopment (hypoplasia) or absence (agenesis) of one or both kidneys; abnormal renal rotation or placement (ectopia); or swelling of the kidneys with the urine (hydronephrosis) due to blockage or narrowing of the tubes (ureters) that carry urine to the bladder.
Some individuals with the disorder may also develop neurological complications due to associated spinal cord injury. Such injury may result from instability of cervical vertebrae. For example, unfused vertebral segments adjacent to fused cervical vertebrae may be abnormally mobile (hypermobile), making them vulnerable to increased stress, which in turn may lead to vertebral instability or degenerative changes. Associated neurological complications tend to develop between the second and third decades of life and may occur spontaneously or following minor trauma. Such complications may include pain; abnormal sensations (paresthesia), such as tingling, prickling, or burning; or involuntary muscle movements accompanying certain voluntary actions (synkinesia or mirror movements). In addition, some individuals may develop increased reflex reactions (hyperreflexia); weakness or paralysis of one side of the body (hemiplegia) or of the legs and the lower part of the body (paraplegia); or impairment of certain nerves that emerge from the brain (cranial nerve palsies).
Diagnosis of Klippel-Feil syndrome
History and Physical
- A thorough and complete history and physical should be performed, including a detailed family genetic history. It is also important to recognize that patients with Klippel-Feil syndrome may be predisposed to congenital spinal stenosis. As such, a relatively low impact or low energy injury may induce a significant neurologic deficit.
- Physical exam findings include shortened neck stature and low-lying hairline. Neurologic symptoms may include radiculopathy and myelopathy. A thorough neurological examination including cranial nerves, sensory, motor, and reflexes, and gait testing along with checking for signs of bowel or bladder incontinence is necessary.
- The doctor observes and/or palpates the head, neck, shoulders, spine, and any other relevant areas of the body to determine where abnormalities may be present.
- The classic complete clinical triad of the low hairline, short neck, and restricted neck motion is only present in 50% of patients with Klippel-Feil syndrome. This variance can be secondary to several factors, such as time dependency of the congenitally-fused cervical patterns assessment and bias associated with the clinical evaluation of the clinical trial.
- The presentation may occur simultaneously with Sprengel deformity, Duane syndrome, renal agenesis, Wildervanck syndrome, and other vascular and cardiac abnormalities. Approximately 50% of patients with Klippel-Feil will present with concurrent scoliosis. Fifty percent may have atlantoaxial instability. Approximately 30% will present with renal disease and 30% with deafness. All other systems require proper evaluation as well.
Lab test and imaging
Laboratory tests should be done to rule out other conditions and assess for organ dysfunctions. The concern should be given to the possible presence of cardiac, gastrointestinal (GI), and urinary disorders and should include an echocardiogram, renal ultrasonogram, and intravenous pyelogram, respectively.[rx][rx][rx][rx] An audiological evaluation for testing hearing would be useful as well. [rx][rx]
- Radiographic evaluation – of the cervical spine in patients with Klippel-Feil syndrome includes plain radiographs (X-rays), computed tomography (CT), and magnetic resonance imaging (MRI). A thorough evaluation of the cervical spine is important prior to procedures like intubation, laryngoscopy, head manipulation, or intraoperative positioning due to the risk of atlantoaxial subluxation and craniovertebral dislocation to avoid any risk of causing spinal cord injury.[rx][rx][rx]
- X-Rays – Commonly performed to illustrate the fusion of the vertebral bodies as well as facets and even spinous processes. The examination should include AP, lateral, and odontoid views in flexion and extension. These studies help to evaluate the stability of the atlantoaxial, atlantooccipital, and subaxial joints. The images of the thoracic and lumbar spine are necessary as well, since they may illustrate scoliosis, spinal Bifida, or hemivertebrae. A wasp-waist sign (anterior-posterior narrowing) may be present. In a clinically stable patient, flexion/extension X-ray may illustrate spinal stability and movement.
- CT – These images would provide additional details about the spinal anatomy and the bony structures, including bony fusion. These studies are especially useful for pre-operative planning when recommended.
- MRI – MRI is useful in assessing the integrity of the spinal cord, disc space, nerve rootlets, ligaments, and rest of the soft tissue structures. This study can also illustrate other spinal cord abnormalities, such as Chiari malformations and diastematomyelia. MRIs are most useful in patients who present with neurologic deficits.
- Genetic testing – A DNA sample may be taken and examined to see if there are mutations in any genes, such as GDF3, GDF6, or MEOX1, which are commonly altered in KFS.
Treatment of Klippel-Feil syndrome
The majority of the patients receive non-operative management unless an acute neurological deficit, a cervical instability, or a risk of chronic neurologic problems is present, where the recommendation is for operative management.[rx][rx]
Non-Operative Management
Overall, treatment is conservative and symptom-driven. For patients with a 1 or 2 level fusions below C3, monitoring and conservative management are sufficient. They may play contact sports such as hockey and rugby with proper education.
Patients who are at high risk for spinal deformity should undergo activity modification. Those with a fusion above C3, especially to the occiput, should avoid contact sports and are more likely to be symptomatic and prone to the risk of spinal injury. This situation also true for those patients with long fusions of the cervical spine.
It is also important to focus on the poly-syndromic presentation of patients. For younger patients, pediatricians play a crucial role in coordinating care between various specialists for cardiac, renal, or gastrointestinal congenital abnormalities. This interdisciplinary care becomes even more vital if patients are candidates for operative care.
If self-care measures do not provide enough pain relief, a doctor may recommend one or more of the following:
- Physical therapy. A physical therapist or another medical professional can design a stretching and strengthening program to fit the patient’s unique needs. A physical therapy program may help improve strength and mobility while reducing some types of pain and stiffness.
- Prescription pain medications. Opioids, also called narcotic pain medications, are a common painkiller used to manage severe pain on a short-term basis. Prescription-strength muscle relaxants may also be used to reduce painful muscle spasms. These medications tend to only be prescribed on a short-term basis due to the risks for serious side effects from long-term use, including addiction.
- Back brace and/or cervical collar. Depending on the amount of spinal deformity, some patients may benefit from wearing a supportive back brace or cervical collar. A back brace may prevent some spinal deformities (such as scoliosis) from worsening as the body continues to grow.
- Injections. Different injections are available that may offer temporary pain relief, depending on the pain source. For example, if a cervical nerve root is inflamed, an anti-inflammatory steroid solution and/or local anesthetic may be injected in the spinal canal’s outer layer to reduce the inflammation.
- Radiofrequency ablation (RFA). This treatment uses a needle to place a heat lesion on a facet joint’s sensory nerves to prevent it from sending out pain signals to the brain. RFA can relieve pain for 6 to 18 months (before the nerve eventually grows back) if indeed the nerve was contributing to pain.
Operative Management
Cervical spinal fusion (arthrodesis) is a surgery that joins selected bones in the neck (cervical spine). There are different methods of doing a cervical spinal fusion:
- Bone can be taken from elsewhere in your body or obtained from a bone bank (a bone graft). The bone is used to make a bridge between vertebrae that are next to each other (adjacent). This bone graft stimulates the growth of new bone. Man-made (artificial) fusion materials may also be used.
- Metal implants can be used to hold the vertebrae together until new bone grows between them.
- Metal plates can be screwed into the bone, joining adjacent vertebrae.
- An entire vertebra can be removed, and the spine then fused.
- A spinal disc can be removed and the adjacent vertebrae fused.
This procedure can be done through an incision on the front (anterior) or back (posterior) of the neck.
Patients with persistent neurological pain, myelopathy, new-onset muscle group weakness, and documented spinal instability are operative candidates.[rx] Spinal deformities and instability drive surgical decision-making. The surgeon can perform cervical fusion from either anterior or posterior approaches secondary to evaluation. The anterior approach includes anterior cervical fusion or corpectomy with the placement of either synthetic or bone graft.[rx] Cervical total disc arthroplasty is under investigation as a surgical option. This modality has shown some positive benefits regarding the quality of life outcomes and prevention of adjacent level disease in the degenerative adult population. Posterior approaches are also options, including decompression and fusion, through a variety of instrumentation procedure options. In some instances of severe deformity, a combined anterior-posterior approach is another option.[rx] Surgical or bracing intervention may be necessary for associated compensatory thoracic scoliosis.[rx]
Otolaryngological evaluation and treatment may be necessary for those with hearing impairment for placing cochlear implants and providing hearing devices where necessary.[rx]
Self-Care for KFS
For neck pain and/or headaches that might be associated with KFS, some potential self-care measures include:
- Activity modification. If certain activities increase pain or present too great a risk, they may need to be avoided or modified. For example, if a child with KFS reports worsening pain when jumping on a trampoline or doing somersaults, those activities should be avoided (if they have not already been forbidden).
- Ice and/or heat therapy. Applying a cold pack or ice may lower inflammation and pain, whereas a heat pack may help loosen tense muscles and increase blood flow to the painful area. To avoid harming the skin, applications tend to be limited to at most 20 minutes at a time with regular checks of the skin. Some people may prefer heat instead of cold, or vice versa.
- Over-the-counter (OTC) medications. Numerous OTC medications are available for reducing pain, which may act as an anti-inflammatory or interfere with pain signals to the brain. It is important to read and follow directions on OTC medications to avoid overdoses and/or harmful interactions.
- Different pillow types. In some cases, a pillow can make a big difference in terms of neck pain at night and/or when waking up. It may help to experiment with pillows of different sizes, shapes, and firmness/fluffiness. Some people even prefer no pillow at all.
Complications
The degenerative changes throughout the cervical spine can lead to the following conditions, which would require monitoring and prompt management. These include:
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Fractures
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Disc degeneration
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Spondylosis
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Spinal canal stenosis
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Disc herniation
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Osteophytes
References
