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.

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.

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.

Genetic Testing Information

• Genetic Testing Registry: Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
• Genetic Testing Registry: Klippel-Feil syndrome
• Genetic Testing Registry: Klippel-Feil syndrome 1, autosomal dominant
• Genetic Testing Registry: Klippel-Feil syndrome 2, autosomal recessive
• Genetic Testing Registry: Klippel-Feil syndrome 3, autosomal dominant

Genetic and Rare Diseases Information Center

• Isolated Klippel-Feil syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• KLIPPEL-FEIL SYNDROME 1, AUTOSOMAL DOMINANT; KFS1
• KLIPPEL-FEIL SYNDROME 2, AUTOSOMAL RECESSIVE; KFS2
• KLIPPEL-FEIL SYNDROME 3, AUTOSOMAL DOMINANT; KFS3
• KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM; KFS4

Scientific Articles on PubMed

• PubMed

• Altuame FD, Haldeman-Englert C, Cupler E, Al Muhaizea MA, Al-Zaidan HI, Hashem M, Alkuraya FS. Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism. Am J Med Genet A. 2021 Feb;185(2):370-376. doi: 10.1002/ajmg.a.61957. Epub 2020 Nov 11. Citation on PubMed
• Bayrakli F, Guclu B, Yakicier C, Balaban H, Kartal U, Erguner B, Sagiroglu MS, Yuksel S, Ozturk AR, Kazanci B, Ozum U, Kars HZ. Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype. BMC Genet. 2013 Sep 28;14:95. doi: 10.1186/1471-2156-14-95. Citation on PubMed or Free article on PubMed Central
• Frikha R. Klippel-Feil syndrome: a review of the literature. Clin Dysmorphol. 2020 Jan;29(1):35-37. doi: 10.1097/MCD.0000000000000301. Citation on PubMed
• Jae-Min Park A, Nelson SE, Mesfin A. Klippel-Feil Syndrome: Clinical Presentation and Management. JBJS Rev. 2022 Feb 15;10(2). doi: 10.2106/JBJS.RVW.21.00166. Citation on PubMed
• Klimo P Jr, Rao G, Brockmeyer D. Congenital anomalies of the cervical spine. Neurosurg Clin N Am. 2007 Jul;18(3):463-78. doi: 10.1016/j.nec.2007.04.005. Citation on PubMed
• Lampropoulou-Adamidou K, Athanassacopoulos M, Karampinas PK, Vlamis J, Korres DS, Pneumaticos SG. Congenital variations of the upper cervical spine and their importance in preoperative diagnosis. A case report and a review of the literature. Eur J Orthop Surg Traumatol. 2013 Jul;23 Suppl 1:S101-5. doi: 10.1007/s00590-013-1216-z. Epub 2013 Apr 6. Citation on PubMed
• Litrenta J, Bi AS, Dryer JW. Klippel-Feil Syndrome: Pathogenesis, Diagnosis, and Management. J Am Acad Orthop Surg. 2021 Nov 15;29(22):951-960. doi: 10.5435/JAAOS-D-21-00190. Citation on PubMed
• Menger RP, Rayi A, Notarianni C. Klippel Feil Syndrome. 2024 May 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK493157/ Citation on PubMed
• Mohamed JY, Faqeih E, Alsiddiky A, Alshammari MJ, Ibrahim NA, Alkuraya FS. Mutations in MEOX1, encoding mesenchyme homeobox 1, cause Klippel-Feil anomaly. Am J Hum Genet. 2013 Jan 10;92(1):157-61. doi: 10.1016/j.ajhg.2012.11.016. Epub 2013 Jan 3. Citation on PubMed or Free article on PubMed Central
• Royal SA, Tubbs RS, D'Antonio MG, Rauzzino MJ, Oakes WJ. Investigations into the association between cervicomedullary neuroschisis and mirror movements in patients with Klippel-Feil syndrome. AJNR Am J Neuroradiol. 2002 Apr;23(4):724-9. Citation on PubMed
• Samartzis D, Kalluri P, Herman J, Lubicky JP, Shen FH. The extent of fusion within the congenital Klippel-Feil segment. Spine (Phila Pa 1976). 2008 Jul 1;33(15):1637-42. doi: 10.1097/BRS.0b013e31817c0bc2. Citation on PubMed
• Samartzis D, Lubicky JP, Herman J, Shen FH. Faces of Spine Care: From the Clinic and Imaging Suite. Klippel-Feil syndrome and associated abnormalities: the necessity for a multidisciplinary approach in patient management. Spine J. 2007 Jan-Feb;7(1):135-7. doi: 10.1016/j.spinee.2006.05.019. No abstract available. Citation on PubMed
• Samartzis DD, Herman J, Lubicky JP, Shen FH. Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms. Spine (Phila Pa 1976). 2006 Oct 1;31(21):E798-804. doi: 10.1097/01.brs.0000239222.36505.46. Citation on PubMed