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Klippel-Feil syndrome is a bone disorder characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae), which is present from birth. Three major features result from this abnormality: a short neck, a limited range of motion in the neck, and a low hairline at the back of the head. Most affected people have one or two of these characteristic features. Less than half of all individuals with Klippel-Feil syndrome have all three classic features of this condition.
In people with Klippel-Feil syndrome, the fused vertebrae can cause a limited range of movement of the neck and back as well as pain in these areas. The fused vertebrae can also lead to nerve damage in the head, neck, or back. Over time, individuals with Klippel-Feil syndrome can develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Rarely, spinal nerve abnormalities may cause involuntary arm movements in people with Klippel-Feil syndrome. Often the vertebral problems in Klippel-Feil syndrome do not cause health problems until aggravated by a spinal injury, such as a fall or car accident. Affected individuals may develop joint pain (osteoarthritis) around the areas of fused bone. Many people with Klippel-Feil syndrome have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae.
People with Klippel-Feil syndrome may have other features in addition to their spine abnormalities. Some people with this condition have hearing difficulties, genitourinary abnormalities such as malformed kidneys, a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect), an opening in the roof of the mouth (cleft palate), or heart abnormalities. Affected individuals may have underdeveloped shoulder blades that sit abnormally high on the back, a condition called Sprengel deformity.
Klippel-Feil syndrome is estimated to occur in 1 in 40,000 to 42,000 newborns worldwide. Females seem to be affected slightly more often than males.
Mutations in the GDF6 and GDF3 genes can cause Klippel-Feil syndrome. These genes provide instructions for making proteins that belong to the bone morphogenetic protein family, which is involved in regulating the growth and maturation (differentiation) of bone and cartilage. Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. The proteins in this family are regulators of cell growth and differentiation in both embryonic and adult tissue. The GDF6 protein is necessary for the formation of many bones and joints in the limbs, skull, spine, chest, and ribs. The protein is involved in setting up boundaries between bones during skeletal development. While the GDF3 protein is known to be involved in bone and cartilage development, its exact role is unclear.
GDF6 and GDF3 gene mutations that cause Klippel-Feil syndrome likely lead to a reduction in functional protein. While the GDF6 and GDF3 proteins are involved in bone growth, and the GDF6 protein plays a role in the formation of vertebrae, it is unclear how a shortage in these proteins leads to incomplete separation of the vertebrae, specifically the cervical vertebrae, in people with Klippel-Feil syndrome.
Some people with Klippel-Feil syndrome do not have identified mutations in the GDF6 or GDF3 genes. The cause of the condition in these individuals is unknown.
Changes in these genes are associated with Klippel-Feil syndrome.
When Klippel-Feil syndrome is caused by mutations in the GDF6 or GDF3 genes, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Sometimes this condition is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. However, in these cases, the gene involved is unknown. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of Klippel-Feil syndrome and may include treatment providers.
You might also find information on the diagnosis or management of Klippel-Feil syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/klippel-feil-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/klippel-feil-syndrome/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about Klippel-Feil syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
autosomal ; autosomal dominant ; autosomal recessive ; birth defect ; cartilage ; cell ; cleft palate ; differentiation ; embryonic ; gene ; inherited ; injury ; involuntary ; joint ; malformation ; palate ; protein ; recessive ; scoliosis ; stenosis ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.