Klippel-Feil syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Klippel-Feil syndrome is a bone disorder that is characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae). The vertebral fusion is present from birth. Cases of Klippel-Feil syndrome may be classified using the Samartzis classification system. This system divides the condition into three types based on the number of fused vertebrae and whether the fused vertebrae are next to each other (contiguous). According to the Samartzis classification, type I involves a single fusion of two vertebrae, type II involves multiple fused vertebrae that are not contiguous, and type III involves multiple fused vertebrae that are contiguous.

Klippel-Feil syndrome has been described as having three classic features: a short neck, the appearance of a low hairline at the back of the head, and a limited range of motion in the neck. However, less than half of the individuals who have been diagnosed with Klippel-Feil syndrome have all three features. People with Klippel-Feil syndrome may have additional signs and symptoms, and these can vary greatly among affected individuals. Some people with Klippel-Feil syndrome do not have any signs or symptoms.

The fused vertebrae in people with Klippel-Feil syndrome can cause health problems. These include chronic headaches; muscle pain; and an involuntary tensing of the neck, which causes the head to tilt or turn (torticollis). Because some of the cervical vertebrae are fused, this region of the neck can become unstable, which increases the risk of damage to the spinal cord. The fused area of the spine may be more susceptible to trauma, such as a fall or car accident.

Some individuals with Klippel-Feil syndrome have a narrowing of the spinal canal (spinal stenosis) in the neck, which can put pressure on the spinal cord and nerves. This may be more common in those with Klippel-Feil syndrome type III.

People with Klippel-Feil syndrome may have additional skeletal features, such as rib abnormalities or an abnormal side-to-side curvature of the spine (scoliosis). Approximately 20 to 30 percent of affected individuals have a skeletal condition called Sprengel deformity, in which the shoulder blades are underdeveloped and sit abnormally high on the back.

Additional signs and symptoms seen in people with Klippel-Feil syndrome may include a difference in the size and shape of the right and left sides of the face (facial asymmetry), hearing loss, eye abnormalities, or an opening in the roof of the mouth (cleft palate). Abnormalities of the heart or kidneys may also be present.

Some people with Klippel-Feil syndrome have neurological issues, which can include a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect) and a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side (synkinesia).

Klippel-Feil syndrome may occur as a feature of other disorders, such as Wildervanck syndrome or hemifacial microsomia. In these instances, affected individuals have the signs and symptoms of both Klippel-Feil syndrome and the additional disorder.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in one of several different genes can cause Klippel-Feil syndrome. Three of these genes, GDF6, GDF3, and MEOX1, are involved in early bone development. The proteins produced from the GDF6 and GDF3 genes are necessary for the formation of bones and joints, including those in the spine. The protein produced from the MEOX1 gene, called homeobox protein MOX-1, regulates the process of separating vertebrae from one another during early development.

The variants in the GDF6, GDF3, and MEOX1 genes that cause Klippel-Feil syndrome likely cause cells to produce fewer normal proteins from these genes. Although the GDF6, GDF3, and homeobox protein MOX-1 proteins are involved in vertebral development, it is unclear how a shortage of one of these proteins leads to the incomplete separation and fusion of the cervical vertebrae in people with Klippel-Feil syndrome.

In many cases, the exact cause of Klippel-Feil syndrome is not known. Researchers suspect that a combination of genetic factors and environmental factors, such as a disruption of blood flow during critical periods of development, may play a role.

When Klippel-Feil syndrome is a feature of another disorder, it is caused by variants in the genes that cause the other disorder.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

In many cases, Klippel-Feil syndrome is sporadic, which means that the condition occurs in people with no family history of the disorder.

When Klippel-Feil syndrome is caused by variants 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.

When Klippel-Feil syndrome is caused by variants in the MEOX1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

When Klippel-Feil syndrome is a feature of another disorder, it follows the inheritance pattern of the other disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Klippel-Feil syndrome is estimated to occur in 1 in 40,000 newborns. Females are affected slightly more often than males.

The actual incidence of Klippel-Feil syndrome may be higher, as many cases of the condition are not diagnosed until later in life when signs and symptoms worsen. Because the signs and symptoms of Klippel-Feil syndrome can vary greatly, some cases likely remain undiagnosed.

Which doctor should you see?

The suggested department for discussing Klippel-Feil syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Klippel-Feil syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.