Practice Essentials
Klippel-Feil syndrome (KFS; also referred to as cervical vertebral fusion syndrome) is a congenital bone disorder characterized by the abnormal fusion of two or more of the cervical vertebrae. [1]
In 1912, Maurice Klippel and Andre Feil independently provided the first descriptions of KFS in patients who manifested the following:
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Short, webbed neck
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Decreased range of motion (ROM) in the cervical spine
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Low hairline
Feil subsequently classified the syndrome into the following three types:
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Type I - Massive fusion of the cervical spine
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Type II - Fusion of one or two vertebrae
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Type III - Presence of thoracic and lumbar spine anomalies in association with type I or type II KFS
Since the original description, other classification systems have been advocated to describe the anomalies, predict the potential problems, and guide treatment decisions.
In a series of articles, Samartzis et al suggested their own classification system, [2, 3] which stratified patients as follows:
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Type I - Single-level fusion
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Type II - Multiple noncontiguous fused segments
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Type III - Multiple contiguous fused segments
Gray et al [4] described 462 patients with KFS and found that the level of fusion did not greatly affect the incidence of neurologic symptoms. The most frequent level they identified was a defect of the occiput to C1, C2, and C3. These produced the most symptoms; lesions below
Anatomy
Auerbach et al studied spinal cord dimensions in children with KFS. [8] They reviewed magnetic resonance imaging (MRI) studies and clinical records of KFS patients and age-matched controls. Torg-Pavlov ratios were found to be identical in the two groups. The cross-sectional area of the spinal cord was smaller in KFS patients at each level from C2 to C7. These differences were statistically significant, with no differences in the cerebrospinal fluid (CSF) column, suggesting that the cord size is smaller in children with KFS than in control subjects. Four of the 12 children with KFS presented with neurologic symptoms that improved after posterior cervical stabilization.
Samartzis et al studied the extent of fusion in the congenital K-F segment to evaluate the presence and extent of specific fusion patterns across the involved cervical segments. [9] In older patients, complete fusion was more prevalent in regard to C2-C7. In the absence of complete fusion, fusion of the posterior elements was noted more often than fusion of the anterior elements.
In another paper, Samartzis et al reviewed the role of the congenitally fused segments in 29 KFS patients in relation to the space available to the cord (SAC) and associated cervical spine-related symptoms (CSS). [10] They suggested that an arrest of normal vertebral development may affect appositional bone development. The effect on vertebral body width may delay neurologic compromise resulting from the congenital fusion process and subsequent degenerative manifestations.
Etiology
The etiology of KFS and its associated conditions is unknown. The syndrome can present with a variety of other clinical syndromes, including fetal alcohol syndrome, Goldenhar syndrome, and anomalies of the extremities. [11, 12, 13]
Gunderson et al suggested that KFS is a genetic condition, [14] whereas Gray et al found a low incidence of inheritance. [4] Two small studies suggested that mutations of the MEOX1 gene, which codes for mesenchyme homeobox 1, might cause a recessive subtype of the syndrome. [15, 16] A report by Karaca et al suggested that a homozygous frameshift mutation in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway, could give rise to a type of autosomal recessive KFS. [17]
In a study that used multigene panel sequencing with the aim of identifying possible pathogenic genes for KFS, Li et al found 11 pathogenic missense mutations in eight patients, including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB. [18] They found no pathogenic mutations in five previously reported pathogenic genes associated with KFS (GDF6, MEOX1, GDF3, MYO18B, and RIPPLY2).
Other investigators have considered KFS to be some type of global fetal insult, which could explain the other associated conditions. Some have considered it to be a consequence of vascular disruption. [19, 20]
Epidemiology
The true incidence of KFS has not been established with certainty. There is evidence to suggest that KFS may be more prevalent than was once believed, with a high proportion of asymptomatic cases. [21]
Gjorup et al reviewed all of the radiographic cervical spine films from a single hospital in Copenhagen. [22] From these films, they determined an incidence of 0.2 cases per 1000 people.
Brown et al reviewed 1400 skeletons from the Terry collection, which at that time was located at the Washington University School of Medicine. [23] They found an incidence of 0.71%.
Nouri et al, using AOSpine data from the United States and other countries, reviewed MRI studies in a global cohort of 458 patients with degenerative cervical myelopathy and found that KFS was present in 2.0%. [24]
Gruber et al reviewed 2917 cervical computed tomography (CT) scans from the emergency department of a level I trauma center in New York State over a 1-year period with the aim of determining the prevalence of KFS in asymptomatic patients. [25] A total of 17 subjects with the syndrome (eight female, nine male) were identified, for a prevalence of 0.58% (1/172). The levels most commonly fused were C5-6 and C2-3. All subjects were classified as Samartzis type I, and none had cervical scoliosis or cervical spine fractures.
Prognosis
The prognosis for KFS depends on the specific anomalies present. Careful evaluation, consistent follow-up, and coordination with other providers are required to avoid pitfalls and to ensure that no diagnoses are missed. The classification system created by Samartzis et al (see above) is useful for predicting which patients may develop symptoms.
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Posterior photo of a patient with Klippel-Feil syndrome and an anomaly of the occipitocervical junction. The image shows an elevated left shoulder due to a Sprengel anomaly; a short, webbed neck; and a low hairline.
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This patient has Klippel-Feil syndrome and an anomaly of the occipitocervical junction. The patient's flexion and extension after the occipitocervical fusion is demonstrated. His rotation was very limited.
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Flexion of the cervical spine in a patient who had an occipitocervical fusion.
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Anteroposterior radiograph of a patient with Klippel-Feil syndrome showing multiple congenital anomalies and cervical scoliosis
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Lateral radiograph of a patient with Klippel-Feil syndrome showing 2 fused segments separated by an open segment.
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This anteroposterior radiograph of the spine in a patient with Klippel-Feil syndrome demonstrates congenital scoliosis and a Sprengel deformity.
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This radiograph demonstrates an omovertebral bone (marked with 2 arrows). This anomaly limits cervical spine motion.
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This photo demonstrates synkinesia. As the patient attempts to oppose the thumb and finger of the right hand, the same movement occurs involuntarily in the left.
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This intravenous pyelogram was performed before ultrasound was available to image the kidneys. Note unilateral absence of the left kidney.
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Failure of segmentation fusion anomaly in a patient with Klippel-Feil syndrome.
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An anomaly of the occipitocervical junction in a patient with Klippel-Feil syndrome. The anomaly was unstable and was fused.
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Congenital anomaly of the forearm in a patient with Klippel-Feil syndrome.
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Omovertebral bone excision in a patient with Klippel-Feil syndrome.
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Omovertebral bone excision in a patient with Klippel-Feil syndrome.
