KFS is a rare skeletal condition in which there is abnormal union or fusion (congenital synostosis) of two or more bones (vertebrae) within the neck. The spinal column or backbone is made up of 33 irregularly-shaped bones known as vertebrae. These bones are divided into different categories. The first seven vertebrae, beginning at the base of the skull, are known as the cervical vertebrae. KFS primarily affects the cervical vertebrae.
Two overlapping classification systems exist for KFS. The original classification of KFS subtypes (I, II and III) described by Maurice Klippel and Andre Feil and one more recent updated classification of KFS Classes (KF1-4) as described by Clarke and colleagues [Clarke et al 1998]. The original classification differentiate individuals based on the degree of cervical fusion; KFS type I is characterized by extensive fusion of vertebrae of the neck (cervical vertebrae) and the upper back (i.e., upper thoracic vertebrae); type II is characterized by fusion at one or two cervical or thoracic vertebrae; 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 contrast, the classification described by Clarke et al differentiate individuals based on patterns of inheritance, common associated anomalies and the axial level of the most anterior fusion. KF1 is the only class presenting with C1-2 fusion, the very short neck and recessive inheritance of type I, II or III fusion patterns; KF2 is autosomal dominant with the most anterior fusion at C2-3 in association with type I, II or III fusion patterns; KF3 is recessive or has reduced penetrance of isolated fusions between any of the cervical vertebrae except C1-2; KF4 includes cases of Wildervank and Duane syndrome.
The specific symptoms associated with KFS vary greatly from one person to another. Historically, KFS was associated with a classic triad of symptoms, specifically abnormally short neck, Restricted movement of the head and neck, and a low hairline at the back of the head (posterior hairline). However, researchers have determined that these symptoms may define one class of KFS, which accounts for less than 50 percent of affected individuals.
In addition to the fusion of certain vertebrae, KFS can be associated with a wide variety of additional anomalies affecting many different organ systems of the body. The progression and severity of KFS can vary greatly depending upon the specific associated complications and the Class of KFS. Some cases may be mild; others may cause serious, life-long complications.
It is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
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 including facial asymmetry, in which one side of the face appears dissimilar from other side, with one eye higher than the other. There may also be abnormal 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.
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 muscle movements accompanying certain voluntary actions (synkinesia or mirror movements). 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).