Klippel-Feil Syndrome

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Klippel-Feil Syndrome is caused by mutations (changes) in the GDF6, GDF3 or MEOX1 genes. These genes play a role in proper bone development. The protein produced by the GDF6 gene is necessary for the formation of bones and joints including the spine. The protein produced from the GDF3 gene also plays a role in bone development however, the exact involvement is unknown. The protein produced form the MEOX1 gene (homeobox protein MOX-1) controls the process that begins separating vertebrae from each another during early development.  

Klippel-Feil Syndrome caused by mutations in GDF6 and GDF3 genes will lead to reduced function of those proteins. Mutations in the MEOX1 gene lead to a complete lack of the homeobox protein MOX-1. A shortage of these proteins causes incomplete separation of the cervical vertebrae in people with this condition. 

Klippel-Feil Syndrome affects approximately 1 in 40,000 to 42,000 newborns worldwide. Females have shown to be affected slightly more often than males. 

This condition is characterized by the fusion (combining) of 2 or more spinal bones in the neck (cervical vertebrae). Symptoms are present from birth. The most common symptoms include:  

• A low posterior hairline (at the back of the head) 
• A short neck  
• Limited neck range of motion  
• Chronic headaches  
• Pain in both the neck and back  

 However, not all people with KSF have these symptoms. 

 Other symptoms that may be present in patients with KSF include: 

• Scoliosis (curved spine) 
• Cervical dystonia (painful, involuntary tensing of the neck muscles)  
• Genitourinary abnormalities (abnormalities of the reproductive organs and/or urinary system including the kidneys) 
• Cardiac (heart) defects 
• Respiratory (lung) problems 
• Hearing problems  
• Short stature (height significantly below average)  

Klippel-Feil Syndrome can be diagnosed at birth through an in-depth clinical evaluation, identification of characteristic symptoms, and specialized tests.  

Tests may include MRI to identify the open spaces between certain cervical and other vertebrae or other abnormalities in the bones and joints. Other specialised tests may be done to identify other characteristic abnormalities associated with the condition such as hearing impairments or heart defects.  

There is currently no cure for this condition. Treatment is mainly symptomatic and supportive. Treatment depends on the symptoms and severity of the individual person and may be lifelong. Careful evaluation and consistent follow-ups from various specialists are important to not miss any related diagnosis.  

Treatments that may be used include the use of cervical collars, braces, physical therapy, non-steroidal anti-inflammatory drugs and pain medications. Surgery may be necessary in some cases.  

KFS is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents. 

When KFS in caused by mutations in the GDF6 or GDF3 genes, it is inherited in an autosomal dominant pattern. This means that one copy of the altered gene in each cell is enough to cause the disorder. Cases can occur in people with no known family history of the disorder as it can result from a new mutation in the gene. Spontaneous mutations happen during the formation of an egg or sperm cell or during the development of the embryo.

A person affected by an autosomal dominant disorder has a 50% chance of passing the mutated gene to each child. There is also a 50% chance that the child will not inherit the mutated gene.

Genetic counselling can be requested to gain a full explanation.

When KFS is caused by mutations in the MEOX1 gene, it is inherited in an autosomal recessive pattern. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with KFS are carriers.  When both parents are carriers, the risk to the baby in each pregnancy is

• 25% chance (1 in 4) of developing the condition
• 50% chance (1 in 2) for the baby to be a carrier of the condition
• 25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier

All information accurately referenced by Metabolic Support UK, however, should you require access to our references, please contact us by email: contact@metabolicsupportuk.org