Klippel–Feil syndrome (KFS), also known as cervical vertebral fusion syndrome, is a
rare congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck (
cervical vertebrae
In tetrapods, cervical vertebrae (: vertebra) are the vertebrae of the neck, immediately below the skull. Truncal vertebrae (divided into thoracic and lumbar vertebrae in mammals) lie caudal (toward the tail) of cervical vertebrae. In saurop ...
). It can result in a limited ability to move the neck and shortness of the neck, resulting in the appearance of a low hairline. Most people only have one or two of those symptoms so it may not be noticeable without medical imaging.
The syndrome is difficult to diagnose, as it occurs in a group of patients affected with many different abnormalities who can only be unified by the presence of fused or segmental cervical vertebrae. KFS is not always genetic and not always known about on the date of birth.
The disease was initially reported in 1884 by
Maurice Klippel and
André Feil from France. In 1919, André Feil suggested another classification of the syndrome, encompassing not only deformation of the cervical spine, but also deformation of the
lumbar
In tetrapod anatomy, lumbar is an adjective that means of or pertaining to the abdominal segment of the torso, between the diaphragm (anatomy), diaphragm and the sacrum.
Naming and location
The lumbar region is sometimes referred to as the lowe ...
and
thoracic
The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen.
In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main ...
spine.
Signs and symptoms
KFS is associated with many other abnormalities of the body, hence thorough evaluation of all patients with fused cervical vertebrae at birth is required. Furthermore, it is unclear whether KFS is a unique disease, or if it is one part of a spectrum of congenital spinal deformities.
KFS is usually diagnosed after birth. The most common signs of the disorder are restricted mobility of the neck and upper spine and a shortened neck with the appearance of a low hairline at the back of the head.
Associated abnormalities may include:
*
Scoliosis
Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...
(sideways curvature of the spine)
*
Spina bifida
Spina bifida (SB; ; Latin for 'split spine') is a birth defect in which there is incomplete closing of the vertebral column, spine and the meninges, membranes around the spinal cord during embryonic development, early development in pregnancy. T ...
* Problems with the
reproductive organs,
kidneys
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
and the
rib
In vertebrate anatomy, ribs () are the long curved bones which form the rib cage, part of the axial skeleton. In most tetrapods, ribs surround the thoracic cavity, enabling the lungs to expand and thus facilitate breathing by expanding the ...
s
*
Cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...
* Dental problems (delayed
dentition
Dentition pertains to the development of teeth and their arrangement in the mouth. In particular, it is the characteristic arrangement, kind, and number of teeth in a given species at a given age. That is, the number, type, and morpho-physiology ...
,
cavities,
missing teeth)
*
Respiratory problems
*
Heart defects
*
Short stature
Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...
*
Duane syndrome
Duane syndrome is a congenital rare type of strabismus most commonly characterized by the inability of the human eye, eye to move outward. The syndrome was first described by ophthalmologists Jakob Stilling (1887) and Siegmund Türk (1896), and s ...
*
Srb's anomaly
*
Sprengel's deformity
The disorder also may be associated with abnormalities of the head and face,
skeleton
A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...
,
sex organs
A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...
,
muscle
Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
s,
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
and
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
, arms, legs and fingers.
Genetics
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s of the ''
GDF6'', ''
GDF3'' and ''
MEOX1'' gene are associated with KFS.
The cause of the condition is unknown in individuals with KFS who do not have mutations of these two genes. ''GDF6'' and ''GDF3'' provide the body with instructions for making proteins involved in regulating the growth and maturation of bone and cartilage. ''GDF6'' specifically is involved in the formation of vertebral bones, among others, and establishing boundaries between bones in skeletal development. ''GDF3'' is involved with bone and cartilage growth. Mutations of ''GDF6,'' ''GDF3'' and ''MEOX1'' cause a reduced number of functional proteins that are coded by these genes, but it is unclear exactly how a shortage in these proteins leads to incomplete separation of the vertebrae in people with KFS.
However, when the ''GDF6'' gene was removed in mice, the result was the fusion of bones.
These mutations can be inherited in two ways:
*
Autosomal dominant inheritance, where one copy of the altered gene in each cell is sufficient to cause the disorder, is especially associated with C2-C3 fusion.
* Autosomal recessive inheritance, where both copies of a gene contain mutations, is especially associated with C5-C6 fusion.
* Another autosomal dominant form (mapped on locus ''8q22.2''), known as KFS with laryngeal malformation, has been identified. It is also known as segmentation syndrome 1.
Diagnosis
The
heterogeneity
Homogeneity and heterogeneity are concepts relating to the uniformity of a substance, process or image. A homogeneous feature is uniform in composition or character (i.e., color, shape, size, weight, height, distribution, texture, language, i ...
of KFS has made it difficult to outline the
diagnosis
Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...
as well as the
prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
for this disease.
Classification
In 1912,
Maurice Klippel and Andre Feil independently provided the first descriptions of KFS. They described patients who had a short,
webbed neck; decreased range of motion (ROM) in the cervical spine; and a low hairline. Feil subsequently classified the syndrome into three categories:
* Type I—Fusion of C2 and C3 with occipitalization of the
atlas
An atlas is a collection of maps; it is typically a bundle of world map, maps of Earth or of a continent or region of Earth. Advances in astronomy have also resulted in atlases of the celestial sphere or of other planets.
Atlases have traditio ...
. In 1953, further complications were later reported by McRae;
flexion
Motion, the process of movement, is described using specific anatomical terminology, anatomical terms. Motion includes movement of Organ (anatomy), organs, joints, Limb (anatomy), limbs, and specific sections of the body. The terminology used de ...
and
extension is concentrated within the C1 and C2 vertebrae. As with aging, the
odontoid process
In anatomy, the axis (from Latin ''axis'', "axle") is the second cervical vertebra (C2) of the spine, immediately inferior to the atlas, upon which the head rests. The spinal cord passes through the axis.
The defining feature of the axis is its ...
can become hypermobile, narrowing the space where the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
and
brain stem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...
travel (
spinal stenosis
Spinal stenosis is an abnormal narrowing of the spinal canal or neural foramen that results in pressure on the spinal cord or nerve roots. Symptoms may include pain, numbness, or weakness in the arms or legs. Symptoms are typically gradual in ...
).
* Type II—Long fusion below C2 with an abnormal occipital-cervical junction. Similar to the C2-C3 fusion of McRae and could be viewed as a more elaborate variation.
Flexion
Motion, the process of movement, is described using specific anatomical terminology, anatomical terms. Motion includes movement of Organ (anatomy), organs, joints, Limb (anatomy), limbs, and specific sections of the body. The terminology used de ...
, extension, and rotation are all concentrated in the area of an abnormal odontoid process or poorly developed ring of C1 which cannot withstand the effects of aging.
* Type III—A single open interspace between two fused segments. Cervical spine motion is concentrated at single open articulation. This
hypermobility may lead to instability or degenerative
osteoarthritis
Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...
. This pattern can be recognized as the cervical spine is often seen to be at an angle or hinge at this open segment.
A classification scheme for KFS was proposed in 1919 by Andre Feil, which accounted for
cervical,
thoracic
The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen.
In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main ...
, and
lumbar
In tetrapod anatomy, lumbar is an adjective that means of or pertaining to the abdominal segment of the torso, between the diaphragm (anatomy), diaphragm and the sacrum.
Naming and location
The lumbar region is sometimes referred to as the lowe ...
spine
malformations
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities
Disability is the experience of any condition that makes it more difficult for a person to do certain act ...
.
However, in 2006, Dino Samartzis and colleagues proposed three classification-types that specifically addressed the cervical spine anomalies and their associated cervical spine-related symptoms, with additional elaboration on various time-dependent factors regarding this syndrome.
Treatment
Treatment for KFS is symptomatic and may include surgery to relieve cervical or
craniocervical instability and constriction of the spinal cord, and to correct
scoliosis
Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...
.
If symptomatic treatment fails, spinal surgery may provide relief. Adjacent segment disease and scoliosis are two examples of common symptoms associated with Klippel–Feil syndrome, and they may be treated surgically. The three categories treated for types of spinal cord deficiencies are massive fusion of the cervical spine (Type I), the fusion of 1 or 2 vertebrae (Type II), and the presence of thoracic and lumbar spine anomalies in association with type I or type II Klippel–Feil syndrome (Type III).
Adjacent segment disease can be addressed by performing cervical disc arthroplasty using a device such as the Bryan cervical disc prosthesis. The option of the surgery is to maintain range of motion and attenuate the rate of adjacent segment disease advancement without fusion. Another type of arthroplasty that is becoming an alternate choice to
spinal fusion
Spinal fusion, also called spondylodesis or spondylosyndesis, is a surgery performed by Orthopedic surgery#Practice, orthopaedic surgeons or neurosurgeons that joins two or more vertebrae. This procedure can be performed at any level in the spine ...
is
Total Disc Replacement. Total disc replacement objective is to reduce pain or eradicate it.
Spinal fusion
Spinal fusion, also called spondylodesis or spondylosyndesis, is a surgery performed by Orthopedic surgery#Practice, orthopaedic surgeons or neurosurgeons that joins two or more vertebrae. This procedure can be performed at any level in the spine ...
is commonly used to correct spinal deformities such as
scoliosis
Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...
.
Arthrodesis
Arthrodesis, also known as artificial ankylosis or syndesis, is the artificial induction of joint ossification between two bones by surgery. This is done to relieve intractable pain in a joint which cannot be managed by pain medication, splin ...
is the last resort in pain relieving procedures, usually when arthroplasties fail.
Prognosis
The
prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
for most individuals with KFS is good if the disorder is treated early and appropriately. Activities that can injure the neck should be avoided, as they may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable.
In less than 30% of cases, individuals with KFS will present with heart defects. If these heart defects are present, they often lead to a shortened
life expectancy
Human life expectancy is a statistical measure of the estimate of the average remaining years of life at a given age. The most commonly used measure is ''life expectancy at birth'' (LEB, or in demographic notation ''e''0, where '' ...
, the average being 35–45 years of age among males and 40–50 among females. This condition is similar to the heart failure seen in
gigantism
Gigantism (, ''gígas'', "wiktionary:giant, giant", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above average height, average. In humans, this conditi ...
.
Epidemiology
The
prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
of KFS is unknown due to the lack of studies to determine its prevalence. It is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.
Notable cases
Ancient
* A case of a child in
Switzerland
Switzerland, officially the Swiss Confederation, is a landlocked country located in west-central Europe. It is bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. Switzerland ...
was discovered in a
necropolis
A necropolis (: necropolises, necropoles, necropoleis, necropoli) is a large, designed cemetery with elaborate tomb monuments. The name stems from the Ancient Greek ''nekropolis'' ().
The term usually implies a separate burial site at a distan ...
dated between 4500 and 4000 BC.
* In 2009, archaeologists excavating at a
Neolithic
The Neolithic or New Stone Age (from Ancient Greek, Greek 'new' and 'stone') is an archaeological period, the final division of the Stone Age in Mesopotamia, Asia, Europe and Africa (c. 10,000 BCE to c. 2,000 BCE). It saw the Neolithic Revo ...
site of the
Đa Bút culture of northern
Vietnam
Vietnam, officially the Socialist Republic of Vietnam (SRV), is a country at the eastern edge of mainland Southeast Asia, with an area of about and a population of over 100 million, making it the world's List of countries and depende ...
discovered the remains of a young man around age 25, "Burial 9", living between 2000 BC and 1500 BC with Klippel–Feil syndrome, who had apparently been supported by his subsistence-level community for at least a decade before his death.
* The
18th Dynasty
The Eighteenth Dynasty of Egypt (notated Dynasty XVIII, alternatively 18th Dynasty or Dynasty 18) is classified as the first dynasty of the New Kingdom of Egypt, the era in which ancient Egypt achieved the peak of its power. The Eighteenth Dynasty ...
Egyptian pharaoh
Tutankhamun
Tutankhamun or Tutankhamen, (; ), was an Egyptian pharaoh who ruled during the late Eighteenth Dynasty of Egypt, Eighteenth Dynasty of ancient Egypt. Born Tutankhaten, he instituted the restoration of the traditional polytheistic form of an ...
is believed by some to have had Klippel–Feil syndrome, though others dispute this claim.
Contemporary
* English cricketer
Gladstone Small
* "Big" Ed Brown from the TLC series, ''
90 Day Fiancé''.
*
Kansas City Chiefs
The Kansas City Chiefs are a professional American football team based in Kansas City, Missouri. The Chiefs compete in the National Football League (NFL) as a member of the American Football Conference (AFC) West division.
Established in 1959 ...
wide receiver
Justyn Ross.
References
''This article incorporates information in the public domain prepared by th
National Institute of Neurological Disorders and Stroke''
External links
{{DEFAULTSORT:Klippel-Feil syndrome
Congenital disorders of musculoskeletal system
Genodermatoses
Rare syndromes