Klippel-Feil Syndrome is a bone disorder characterized by the abnormal union or fusion of two or more bones in the neck. This condition develops in utero as the result of genetic mutation. Although this syndrome may be evident at the birth of the infant, some of the cases may go undetected as the symptoms may be slight. This condition can develop as the isolated abnormality or in associated with various other syndromes. Klippel-Feil Syndrome is estimated to affect around 1 in 40,000 to 42,000 newborns globally.
Causes
Klippel-Feil Syndrome develops as the result of mutations in the GDF6, GDF3 or MEOX1 genes which are all involved in the bone development. The mutation in the MEOX1 affects the normal production of the protein known as homeobox protein (MOX-1) that is responsible for the separation of the vertebrae from each other during development. The proteins produced by the GDF6 and GDF3 are essential for the development of bones and the joints. The genetic mutation of the GDF6 and GDF3 genes causes the reduced functions of their respective proteins which result in the features of this syndrome. The GDF6 and GDF3 gene can be inherited in an autosomal dominant pattern where one copy of the defective gene can cause the disorder. The MEOX1 gene is inherited in an autosomal recessive pattern where both the copies of the genes from the parents have mutations.
Symptoms
The symptoms of Klippel-Feil Syndrome includes the fusion of two or more spinal bones in the neck, a condition called torticollis where the head is positioned to one side and the chin to the other, spina bifida which is the incomplete closing of the neural tube, curvature of the spine, webbed fingers (syndactyly) and abnormality of the thumb (hypoplastic thumb). They may also exhibit cleft palate, hearing problems, underdeveloped shoulder blades (sprengel’s deformity) and a condition known as synkinesia where the movement of one hand involuntarily mimics the other. In addition, they may also present respiratory problems, malformations of the kidney, rib and the heart along with neurological deficits.
Diagnosis
The diagnosis of Klippel-Feil Syndrome is based on the clinical evaluation, identification of features associated with this condition and various specialized tests. The MRI can determine the open spaces between the vertebrae and the extent of bone fusion. Various other specialized tests may be necessary to characterize additional abnormalities such as the congenital heart defects, eye problems and the renal abnormalities.
Treatment
The treatment for the affected individuals is based on the various symptoms that are evident in each case. The therapy for this syndrome can include measures such as the use of braces, cervical collars and non-steroidal anti-inflammatory medications. They may also require surgical intervention to repair the skeletal, cardiac and renal abnormalities. Individuals with the hearing problems may benefit from the hearing aids. As these cases are at increased risk of developing neurological complications, they need to be regularly monitored. In some of the cases, the genetic counseling may also be beneficial for the affected individuals and their families.
References
https://rarediseases.org/rare-diseases/klippel-feil-syndrome/
http://www.chop.edu/conditions-diseases/klippel-feil-syndrome
https://ghr.nlm.nih.gov/condition/klippel-feil-syndrome#statistics
