Klippel-Feil Syndrome

In 1912 Maurice Klippel and André Feil described a syndrome that is now called Klippel-Feil syndrome. It is caused by a failure in the normal segmentation of the cervical vertebrae during the early weeks of fetal development. Features include a short neck, restricted mobility of the upper spine and a low hairline. Any of the cervical vertebrae can be involved but the most common fusion is of C2-C3.

• Klippel-Feil syndrome is due to mutation on the long arm of chromosome 8 at 8q22.2 and is inherited as an autosomal dominant disorder with limited penetrance.¹
• Klippel-Feil malformation is an autosomal recessive disorder with mutation on 5q11.2.² C5-C6 fusion is more likely to be an autosomal recessive disorder.

There are 3 types of cervical vertebral fusion:³

• Type I is massive fusion of many cervical and upper thoracic vertebrae into bony blocks.
• Type II is fusion at only one or two interspaces, although hemivertebrae, occipito-atlantal fusion and other anomalies might also occur.
• Type III is both cervical fusion and lower thoracic or lumbar fusion.

An alternative classification has been proposed that is said to give a better reflection of prognosis:⁴

• Type I patients have a single congenitally fused cervical segment.
• Type II patients have multiple noncontiguous, congenitally fused segments.
• Type III patients have multiple contiguous, congenitally fused cervical segments.

In the review, 36% of patients had cervical spine-related symptoms and the majority had axial symptoms. Axial neck symptoms were highly associated with type I patients, whereas predominant radicular and myelopathic symptoms occurred in type II and type III patients.

It is impossible to give figures for the incidence of the condition as it is highly variable in presentation and not all cases are recognised. The form of inheritance is also variable.

Clinical presentation is varied because of the many associated syndromes and anomalies that can occur.⁵ Presentation may occur at any time in life, often as an incidental finding. It may occur with fetal alcohol syndrome (FAS).⁶

• Upper cervical spine involvement tends to present at an earlier age than involvement of the lower cervical spine.
• Decreased range of movement of the neck is the most consistent finding with loss of rotation being more pronounced than loss of flexion and extension.
• A low hairline occurs in 40 to 50%.
• About 20% have neurological problems. These may be produced by hypermobility. Some patients present with pain. Scoliosis may be congenital or acquired and affects around 60%. Sometimes there is a compensatory scoliosis. High cervical abnormalities can cause acute spinal cord compression following comparatively minor trauma.
• Synkinesia is mirror movement of the upper extremity in which patients are unable to perform a movement of the right hand without performing the same movement of the left hand.⁷ This is disabling in everyday activities. It may be improved with therapy and usually improves with age.
• Associated abnormalities may include scoliosis, spina bifida, anomalies of the kidneys and the ribs, cleft palate, respiratory problems and heart malformations. There may also be abnormalities of the head and face, skeleton, genitals, muscles, brain and spinal cord, arms, legs and fingers.
• Many and varied abnormalities of the renal system have been reported in as many as a third of cases.
• Torticollis and facial asymmetry with possible craniofacial anomalies affect between a quarter and a half of all sufferers.
• The hearing loss can be sensorineural, conductive or mixed, as there are many possible defects in the ear.⁸ One study found deafness in 35 of 44 - or 80%.⁹
• Cardiovascular anomalies occur in 15 to 30% of cases. The most common problem is ventricular septal defect.

The extent of investigation will depend upon the age of presentation, the nature of the problem and other confounding issues. It may be part of assessing the need for surgery to stabilise the neck. Such surgery carries risks, and intubation for anaesthesia can be dangerous.

• Anteroposterior (AP) and lateral views of the cervical spine are basic. If abnormalities are present, carefully assessment of the atlanto-occipital joint is required. Various other views may be required.
• Chest X-ray may show cardiac abnormalities or fusion of ribs.
• CT scan can be very useful at the base of the skull, especially if abnormalities are unilateral.
• MRI scan is useful to assess the spinal canal and any abnormalities of the spinal column, such as syringomyelia.
• Ultrasound is used for imaging of the urinary tract. Intravenous pyelogram (IVP) may also be required.
• All children should have an assessment of hearing.
• If there are features of FAS but the mother is not known to be an alcohol abuser then tactful enquiry and investigation as outlined in articles on alcoholism, is required.

• Associated abnormalities, e.g. cleft palate and/or heart or renal anomalies, may require surgical correction.
• Management of hearing impairment when required.
• Avoidance of trauma is important. A person with no neck may seem an ideal candidate for the front row of a scrum but this would be extremely dangerous.
• Genetic counselling may be required.

Surgery

Surgical intervention may be required in a variety of situations:

• Fusion anomalies and the difference in growth potential between the two sides of the spine can make deformity progressive.
• Instability of the cervical spine requires fixation. Instability of the cervical spine can develop between two sets of fusion anomalies separated by a normal segment.
• Neurological deficits or persistent pain require surgery.
• Development of a compensatory curve in the thoracic spine may require surgical intervention or bracing.
• Symptomatic spinal stenosis may require decompression and fusion.

The prognosis for Klippel-Feil syndrome depends on the specific associated anomalies.

1. OMIM - Klippel-Fiel syndrome.
2. OMIM - Klippel-Fiel malformation
3. Gunderson CH, Greenspan RH, Glaser GH, et al; The Klippel-Feil syndrome: genetic and clinical reevaluation of cervical fusion. Medicine (Baltimore). 1967 Nov;46(6):491-512.
4. Samartzis DD, Herman J, Lubicky JP, et al; Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms. Spine. 2006 Oct 1;31(21):E798-804. [abstract]
5. Hensinger RN, Lang JE, MacEwen GD; Klippel-Feil syndrome; a constellation of associated anomalies. J Bone Joint Surg Am. 1974 Sep;56(6):1246-53. [abstract]
6. Tredwell SJ, Smith DF, Macleod PJ, et al; Cervical spine anomalies in fetal alcohol syndrome. Spine. 1982 Jul-Aug;7(4):331-4. [abstract]
7. Royal SA, Tubbs RS, D'Antonio MG, et al; Investigations into the association between cervicomedullary neuroschisis and mirror movements in patients with Klippel-Feil syndrome. AJNR Am J Neuroradiol. 2002 Apr;23(4):724-9. [abstract]
8. Ohtani I, Dubois CN; Aural abnormalities in Klippel-Feil syndrome. Am J Otol. 1985 Nov;6(6):468-71. [abstract]
9. McGaughran JM, Kuna P, Das V; Audiological abnormalities in the Klippel-Feil syndrome. Arch Dis Child. 1998 Oct;79(4):352-5. [abstract]

• Sullivan JA; Klippel-Feil syndrome; emedicine June 2009.
• Contact a Family; UK support site, information and ability to support
• wheelessonline.com; Klippel Feil syndrome