Information on the following diseases can be found in the Related Disorders section of this report:

• Wildervanck Syndrome
• Associated Syndromes (General)

Klippel-Feil syndrome (KFS) is a rare skeletal condition in which there is abnormal union or fusion (congenital synostosis) of two or more bones of the spinal column (vertebrae) within the neck. Researchers have described three major subtypes of the condition. According to this classification, KFS type I is characterized by extensive fusion of vertebrae of the neck (cervical vertebrae) and the upper back (i.e., upper thoracic vertebrae). In KFS type II, there is localized union or fusion at one or two cervical or thoracic vertebrae. In addition, type II is often associated with additional skeletal abnormalities, such as incomplete development of one half of certain vertebrae (hemivertebrae) and fusion of the first vertebra of the neck (atlas) with the bone at the back of the skull (occipital bone). KFS type III is characterized by fusion of vertebrae of the neck as well as vertebrae of the upper or lower back (i.e., lower thoracic or lumbar vertebrae). In addition, some investigators have suggested a fourth subtype in which KFS is associated with absence (agenesis) of the fused bones that form the relatively large triangular bone in the lower spine (sacrum).

Some individuals with KFS also have an unusually short neck that may appear webbed (pterygium-like), limited movement of the head and neck, and a low hairline at the back of the head (posterior hairline) that may extend to the shoulders. In addition, approximately 30 percent of affected individuals have additional skeletal abnormalities, such as fusion of certain ribs or other rib defects; abnormal sideways curvature of the spine (scoliosis); or a condition known as Sprengel's deformity. This condition is characterized by elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the shoulder blade. Also, in some individuals with KFS, a portion of the spinal cord may be exposed due to incomplete closure of certain vertebrae (spina bifida occulta). Associated findings may include the presence of a tuft of hair or dimple over the underlying abnormality and, in some cases, leg weakness, an inability to control urination (urinary incontinence), or other findings. As mentioned above, KFS type II may be associated with incomplete development of one half of certain vertebrae (hemivertebrae) and fusion of the first vertebra of the neck (atlas) with the bone at the back of the skull (occipital bone).

Approximately 25 to 50 percent of individuals with KFS also have hearing impairment. Such hearing loss may result from impaired transmission of sound from the outer or middle ear to the inner ear (conductive hearing loss); failed transmission of sound impulses from the inner ear to the brain (sensorineural hearing loss); or both (mixed hearing loss). Various eye (ocular) abnormalities may also be associated with KFS, such as deviation of one eye toward the other (cross-eye or convergent strabismus); involuntary, rapid eye movements (nystagmus); or absence or defects of ocular tissue (colobomas). In addition, some affected individuals may have other abnormalities of the head and facial (craniofacial) area. For example, in some cases, the face appears dissimilar from one side to the other (facial asymmetry), with one eye higher than the other. There may also be twisting of the neck (torticollis), causing the head to be rotated into an abnormal position. According to some reports, approximately 17 percent of individuals with KFS also have incomplete closure of the roof of the mouth (cleft palate).

KFS may sometimes be associated with additional physical abnormalities. These may include structural malformations of the heart (congenital heart defects), particularly ventricular septal defects (VSDs). VSDs are characterized by the presence of an abnormal opening in the fibrous partition (septum) that separates the two lower chambers of the heart. Some individuals may also have kidney (renal) defects, such as underdevelopment (hypoplasia) or absence (agenesis) of one or both kidneys; abnormal renal rotation or placement (ectopia); or swelling of the kidneys with urine (hydronephrosis) due to blockage or narrowing of the tubes (ureters) that carry urine to the bladder. Less commonly, mental retardation has also been reported in association with KFS.

Some individuals with the disorder may also develop neurological complications due to associated spinal cord injury. Such injury may result from instability of cervical vertebrae. For example, unfused vertebral segments adjacent to fused cervical vertebrae may be abnormally mobile (hypermobile), making them vulnerable to increased stress, which in turn may lead to vertebral instability or degenerative changes. Associated neurological complications tend to develop between the second and third decades of life and may occur spontaneously or following minor trauma. Such complications may include pain; abnormal sensations (paresthesia), such as tingling, prickling, or burning; or involuntary movements accompanying the performance of certain voluntary actions (synkinesia). In addition, some individuals may develop increased reflex reactions (hyperreflexia); weakness or paralysis of one side of the body (hemiplegia) or of the legs and the lower part of the body (paraplegia); or impairment of certain nerves that emerge from the brain (cranial nerve palsies).

In most individuals with Klippel-Feil syndrome (KFS), the condition appears to occur randomly for unknown reasons (sporadically). However, in other cases, familial patterns have been reported that may suggest autosomal dominant or autosomal recessive inheritance. Researchers indicate that various genetic and possibly environmental factors may play some causative role.

In those with KFS type I, the condition usually occurs sporadically. However, there have been a few familial cases reported; some researchers indicate that such cases may suggest autosomal recessive transmission. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In autosomal recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

KFS type II usually appears to be transmitted as an autosomal dominant trait with variable expressivity. In autosomal dominant disorders, a single copy of a disease gene (received from either the mother or father) may be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disease gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. In autosomal dominant disorders with variable expressivity, the characteristics that are manifested may vary greatly in range and severity from case to case.

Some researchers suggest that type II may result from different disease genes (genetic heterogeneity) and may sometimes be transmitted as an autosomal recessive trait. In addition, some researchers suggest that KFS type III may have autosomal recessive inheritance.

The specific underlying cause or causes of the abnormalities associated with KFS remain unknown. However, the condition appears to result from failure of the proper division (segmentation) of embryonic tissue that develops into certain vertebrae. In addition, some investigators suggest that KFS may in some cases be due to disruption of blood flow through particular arteries (subclavian artery supply disruption) during early embryonic growth. Further research is needed to learn more about the various underlying mechanisms that may be responsible for KFS.
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Klippel-Feil syndrome (KFS) was originally described in the medical literature in 1912 (M. Klippel). Reports suggest that the condition occurs in approximately one in 42,000 births. KFS affects females more frequently than males. More specifically, approximately 65 percent of affected individuals are female. According to reports in the medical literature, type II appears to be the most common form of the condition.

Symptoms of the following disorder may be similar to those of Klippel-Feil syndrome (KFS). Comparisons may be useful for a differential diagnosis:

Wildervanck syndrome, also known as cervicooculoacoustic syndrome, is a rare genetic disorder that may be detected during infancy. The disorder is characterized by KFS; hearing impairment due to failed transmission of sound impulses from the inner ear to the brain (sensorineural deafness); and a condition known as Duane syndrome in which there are abnormalities of certain eye (ocular) movements. Duane syndrome is primarily characterized by limitation or absence of certain horizontal eye movements; retraction or "drawing back" of the eyeball into the eye cavity (orbit) upon looking inward; and, in some cases, abnormal deviation of one eye in relation to the other (strabismus). In addition, in some individuals with Wildervanck syndrome, the face may appear dissimilar from one side to the other (facial asymmetry). According to reports in the medical literature, Wildervanck syndrome primarily affects females. The disorder has appeared to occur randomly for unknown reasons (sporadically). Some researchers suggest that Wildervanck syndrome may result from the interaction of several different genes (polygenic). (For further information, please choose "Wildervanck" as your search term in the Rare Disease Database.)

There are a number of additional syndromes in which KFS may occur in association with other characteristic physical findings. Such syndromes include MURCS association; Goldenhar syndrome, also known as oculo-auriculo-vertebral (OAV) spectrum; and other disorders. (For further information, choose "MURCS," "Goldenhar," or the exact disease name in question as your search term in the Rare Disease Database.)

Diagnosis
Klippel-Feil syndrome (KFS) may be diagnosed at birth based upon a thorough clinical evaluation, identification of characteristic physical findings, and specialized tests. Diagnostic studies may include advanced imaging techniques, such as magnetic resonance imaging (MRI), to help characterize the open spaces (interspaces) between certain cervical and other vertebrae, the extent of abnormal vertebral union or fusion, and possible impingement of vertebrae on the spinal cord. (During MRI, a magnetic field and radio waves form detailed cross-sectional images of internal structures.) Additional specialized tests may also be conducted to help detect and/or characterize other abnormalities that may be associated with KFS (e.g., hearing impairment, congenital heart defects, renal abnormalities, eye defects, etc.).

Treatment
The treatment of Klippel-Feil syndrome (KFS) is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; surgeons; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); physicians who specialize in neurological disorders (neurologists); physicians who diagnose and treat heart abnormalities (cardiologists); specialists who assess and treat hearing problems (audiologists); eye specialists (ophthalmologists); and/or other health care professionals.

Because some affected individuals may have an increased risk of neurological complications, they should be regularly monitored by physicians. In addition, they should avoid activities that could lead to trauma or injury to cervical vertebrae.

In some individuals with KFS, treatment may include surgical repair of certain skeletal, auditory, ocular, cardiac, renal, or other abnormalities potentially associated with the disorder. For example, in those with cervical spinal cord compression, surgery may be conducted to correct such compression or associated vertebral instability. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors. In addition, some individuals with hearing impairment may benefit from the use of specialized hearing aids. Other treatment is symptomatic and supportive.

Early intervention may be important in ensuring that children with KFS reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with KFS and their families.

Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project, which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No: 148900; Last Update: 2/18/99. Entry No: 118100; Last Update 2/18/99. Entry No: 214300; Last Update: 2/18/99. Entry No: 314600; Last Update: 4/18/94.

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Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:886-89.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:653-54, 1015-16.

JOURNAL ARTICLES
Clarke RA, et al. Heterogeneity in Klippel-Feil syndrome: a new classification. Pediatr Radiol. 1998;28:967-74.

McGaughran JM, et al. Audiological abnormalities in the Klippel-Feil syndrome. Arch Dis Child. 1998;79:352-55.

Rouvreau P, et al. Assessment and neurologic involvement of patients with cervical spine congenital synostosis as in Klippel-Feil syndrome: study of 19 cases. J Pediatr Orthop B. 1998;7:179-85.

Thompson E, et al. Autosomal dominant Klippel-Feil anomaly with cleft palate. Clin Dysmorphol. 1998;7:11-15.

Theiss SM, et al. The long-term follow-up of patients with Klippel-Feil syndrome and congenital scoliosis. Spine. 1997;22:1219-22.

Thomsen MN, et al. Scoliosis and congenital anomalies associated with Klippel-Feil syndrome types I-III. Spine. 1997;22:396-401.

Oeken J, et al. Middle ear abnormalities in Klippel-Feil syndrome. HNO. 1996;44:521-25.

Raas-Rothschild A, et al. Klippel-Feil anomaly with sacral agenesis: an additional subtype, type IV. J Craniofac Genet Dev Biol. 1988;8:297-301.

Brill CB, et al. Isolation of the right subclavian artery with subclavian steal in a child with Klippel-Feil anomaly: an example of the subclavian artery supply disruption sequence. Am J Med Genet. 1987;26:933-40.

Bavinck JN, et al. Subclavian artery supply disruption sequence: hypothesis of a vascular etiology for Poland, Klippel-Feil, and Mobius anomalies. Am J Med Genet. 1986;23:903-18.

Juberg RC, et al. Cervical vertebral fusion (Klippel-Feil) syndrome with consanguineous parents. J Med Genet. 1976;13:246-49.

Gunderson CH, et al. The Klippel-Feil syndrome: genetic and clinical reevaluation of cervical fusion. Medicine. 1967;46:491-512.