Overview

Klippel-Feil syndrome (KFS) is a rare congenital condition (it develops before or is present at birth) that results in the abnormal fusion of two or more small bones (vertebrae) within the neck. Usually, this occurs during foetal development and is indicated by a triad of features, such as a shortened neck, limited neck movement, and a low hairline at the back of the head. In addition, this abnormality can cause facial asymmetry and persistent headaches.¹ 

About 1 in 50,000 people are affected by KFS. The exact cause of the condition is not known; however, the syndrome can be attributed to abnormalities inherited from parents in several genes that are essential for healthy bone development, such as GDF6, GDF3, and MEOX1.^2,3 

Currently, there is no known cure for KFS. Therefore, healthcare professionals treat the symptoms exhibited by patients and support them to have a better quality of life.¹ 

Other symptoms experienced by patients with this syndrome include heart, lung, and hearing issues. Furthermore, some cases of KFS manifest with several syndromes, and the condition could predispose individuals to cervical spinal deformities such as scoliosis, instability, and neurological impairments.⁴ 

This associated syndrome includes:¹

• Foetal alcohol syndrome
• Goldenhar syndrome
• Sprengel deformity

It is noteworthy that patients with KFS may have no signs or symptoms present (asymptomatic), and the condition is often only detected by imaging tests for unrelated incidents, such as falls or accidents. It is possible to diagnose KFS within the first trimester of pregnancy; however, there are cases where pre-natal imaging is not completed or KFS is not detectable in babies who do not exhibit a serious physical abnormality. As a consequence, some people may not be aware of their condition until they are adults. The diagnosis of KFS is typically made through a combination of medical history, clinical evaluation, imaging, and genetic testing.^1,5,6 

Diagnosis of klippel-feil syndrome 

Medical history and clinical evaluation

The diagnostic process often starts with a medical evaluation. Depending on the number of fused vertebrae and the location of the fusion in the neck and spine, KFS can present with a wide range of symptoms. To get a medical history and physical examination, the healthcare professional will ask a series of questions to understand previous conditions or illnesses, treatments, lifestyle, and familial health.^1,5 

A physical examination would usually be conducted to possibly:¹

• Examine the spine, face, neck (to determine whether it is short), and hairline (to establish whether it is low at the back of your head)
• Check for symptoms of myelopathy (to determine whether compression has damaged your spinal cord)
• To check microcephaly ( a smaller-than-average head size)
• To check for symptoms of radiculopathy (to determine whether the cervical spine is squeezing a nerve)
• A neurological exam is likely to be conducted to assess reflexes or muscle weakness
• Examine the patient’s walk
• Feel and listen to the patient’s chest

Imaging tests 

Following consultation with a healthcare professional, imaging studies are often performed to confirm the diagnosis and identify the cause within the body.

X-rays

X-rays are often the first imaging test done. This is because they give us a fast, clear look at the bones in the neck and can show fused bones within the body. X-ray imaging will be taken from many sides (front, side, and open mouth) to fully see the neck and spine. For a  lot of patients, this is all they need to highlight bone fusion, which is often the main sign of KFS.¹

MRI (magnetic resonance imaging)

Additionally, healthcare professionals could request MRI testing as these scans are better suited to show soft tissues within the neck and spine.^1,5,7 

They assist diagnosis by:⁷

• Visualising fusions: MRI depicts the extent and location of vertebral fusions, which is a hallmark of the syndrome
• Assessing spinal cord and nerve compression: MRI can identify whether the fused vertebrae are compressing the spinal cord or nerve roots, which can lead to neurological symptoms 
• Detecting associated anomalies: KFS can be associated with other abnormalities, such as Chiari malformation, syringomyelia, or other spinal cord or brainstem issues 

CT scan (computed tomography)

A computed tomography scan (CT scan)  provides a more detailed and three-dimensional picture of bones than a standard X-ray. While X-rays are a recommended option for getting an overall picture of the neck and spine, they might not reveal small or complex abnormalities, especially in areas where bones are irregularly shaped or fused. Alternatively, CT scans take a series of X-rays from various angles to create cross-sectional images, enabling doctors to view the shape of each vertebra more clearly and precisely.⁸

The level of detail in CT scans is particularly helpful in confirming subtle or complicated vertebral fusions, which might not be obvious on a normal X-ray. For example, if a fusion is only occurring in part of a vertebra or is occurring in an unusual pattern, a CT scan can make it easier to detect. In addition, CT scans can reveal related issues like bone spurs, misalignments, or other bony abnormalities that might be responsible for a patient's symptoms, such as pain or limited range of motion.⁸

Genetic testing 

In most instances, healthcare professionals would consider genetic testing to determine the underlying cause of KFS, especially if:^1,5

• The patient has other congenital defects
• There is a family history of genetic disorders
• Diagnosis is still unclear, or they are exhibiting rare signs or symptoms 

Types of genetic tests

These tests are often done from just a small sample of blood or saliva taken from a patient. The samples are sent to a specialist laboratory, and some of the tests that could be conducted include:

• Targeted gene panel: Looks at certain genes known to lead to KFS
• Whole exome sequencing (WES): Checks all the protein-making parts of the DNA⁹
• Chromosomal microarray: Identifies big genetic changes such as missing parts or duplicate genes¹⁰

Genetic testing is important because understanding the genetic element of KFS helps to confirm the diagnosis in complex cases. Additionally, it can predict the risk of passing KFS to any future offspring. Notably, genetic testing could help in planning a personalised treatment regimen as healthcare professionals know which genes are affected.^9,10

Other specialised testing and a multidisciplinary approach 

Other specialised tests can be recommended to examine any other abnormalities associated with the condition, such as hearing impairments, lung problems, or heart defects. As the syndrome can affect multiple bodily systems, a multidisciplinary team will often work together to diagnose and treat the symptoms associated with the condition.¹

This could include:

• Cardiologists and nephrologists: for heart and kidney evaluations
• ENT specialists: for hearing issues
• Genetic counsellors: to explain test results and inheritance patterns
• Neurologists: for nerve and brain-related symptoms
• Orthopaedic specialists: for neck and spine problems

Summary 

Klippel-Feil syndrome (KFS) is a rare congenital condition that is characterised by the fusion of two or more vertebrae in the neck; this abnormal fusion of vertebrae can result in different symptoms. The triad of symptoms typically associated with KFS includes limited neck mobility, a short neck, and a low hairline at the back of the head. Although these are the most associated symptoms of the condition, not all patients will exhibit all or any symptoms at birth. 

Some patients could have mild symptoms and will proceed to adulthood without knowing they have the condition. Other symptoms associated with the syndrome include facial asymmetry, hearing, heart, or lung issues, scoliosis, and neurological abnormalities. The diagnosis of KFS usually encompasses three main components:

• Clinical evaluation: A healthcare professional will compile medical history by asking a series of questions on topics such as past medical conditions, familial history, and lifestyle. They will conduct a physical test by looking at physical indicators such as limited neck movement, a short neck, or a low hairline
• Imaging studies: Verifying spinal fusion and looking for associated anomalies using X-rays, MRIs, and CT scans
• Genetic testing: Finding certain gene alterations that could account for the syndrome and help guide future family planning

Other specialised testing can be requested by healthcare professionals to understand the effect that the syndrome could have on other bodily systems. By involving a multidisciplinary team in the diagnosis of this rare condition, an accurate diagnosis can be made, and healthcare professionals can support patients during the treatment of symptoms associated with the syndrome.