Klippel–Feil syndrome (KFS), also known as cervical vertebral fusion syndrome, is a rare congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck (cervical vertebrae). It can result in a limited ability to move the neck and shortness of the neck, resulting in the appearance of a low hairline. Most people only have one or two of those symptoms so it may not be noticeable without medical imaging. The syndrome is difficult to diagnose, as it occurs in a group of patients affected with many different abnormalities who can only be unified by the presence of fused or segmental cervical vertebrae. KFS is not always genetic and not always known about on the date of birth. The disease was initially reported in 1884 by Maurice Klippel and André Feil from France. In 1919, in his Doctor of Philosophy thesis, André Feil suggested another classification of the syndrome, encompassing not only deformation of the cervical spine, but also deformation of the lumbar and thoracic spine.

Signs and symptoms

KFS is associated with many other abnormalities of the body, hence thorough evaluation of all patients with fused cervical vertebrae at birth is required. Furthermore, it is unclear whether KFS is a unique disease, or if it is one part of a spectrum of congenital spinal deformities. 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: The disorder also may be associated with abnormalities of the head and face, skeleton, sex organs, muscles, brain and spinal cord, arms, legs and fingers.

Genetics

Mutations of the GDF6, GDF3 and MEOX1 gene are associated with KFS. The cause of the condition is unknown in individuals with KFS who do not have mutations of these two genes. GDF6 and GDF3 provide the body with instructions for making proteins involved in regulating the growth and maturation of bone and cartilage. GDF6 specifically is involved in the formation of vertebral bones, among others, and establishing boundaries between bones in skeletal development. GDF3 is involved with bone and cartilage growth. Mutations of GDF6, GDF3 and MEOX1 cause a reduced number of functional proteins that are coded by these genes, but it is unclear exactly how a shortage in these proteins leads to incomplete separation of the vertebrae in people with KFS. However, when the GDF6 gene was removed in mice, the result was the fusion of bones. These mutations can be inherited in two ways:

Diagnosis

The heterogeneity of KFS has made it difficult to outline the diagnosis as well as the prognosis for this disease.

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 three categories: A classification scheme for KFS was proposed in 1919 by Andre Feil, which accounted for cervical, thoracic, and lumbar spine malformations. 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.

Treatment

Treatment for KFS is symptomatic and may include surgery to relieve cervical or craniocervical instability and constriction of the spinal cord, and to correct scoliosis. If symptomatic treatment fails, spinal surgery may provide relief. Adjacent segment disease and scoliosis are two examples of common symptoms associated with Klippel–Feil syndrome, and they may be treated surgically. The three categories treated for types of spinal cord deficiencies are massive fusion of the cervical spine (Type I), the fusion of 1 or 2 vertebrae (Type II), and the presence of thoracic and lumbar spine anomalies in association with type I or type II Klippel–Feil syndrome (Type III). Adjacent segment disease can be addressed by performing cervical disc arthroplasty using a device such as the Bryan cervical disc prosthesis. The option of the surgery is to maintain range of motion and attenuate the rate of adjacent segment disease advancement without fusion. Another type of arthroplasty that is becoming an alternate choice to spinal fusion is Total Disc Replacement. Total disc replacement objective is to reduce pain or eradicate it. Spinal fusion is commonly used to correct spinal deformities such as scoliosis. Arthrodesis is the last resort in pain relieving procedures, usually when arthroplasties fail.

Prognosis

The prognosis for most individuals with KFS is good if the disorder is treated early and appropriately. Activities that can injure the neck should be avoided, as they may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable. In less than 30% of cases, individuals with KFS will present with heart defects. If these heart defects are present, they often lead to a shortened life expectancy, the average being 35–45 years of age among males and 40–50 among females. This condition is similar to the heart failure seen in gigantism.

Epidemiology

The prevalence of KFS is unknown due to the lack of studies to determine its prevalence. It is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.

Notable cases

Ancient

Contemporary