INTRODUCTION:
The Cervical vertebra is 7 in number. Vertebrae
(vertebral column and intervertebral disc) may be fused as a result of a
congenital anomaly, manifestations of which can be seen in the cervical, lumbar
or thoracic region [1]. Vertebral synostosis in the vertebral region is called
Klippel-Feil syndrome, in the Lumbar region, its called block vertebra and in
the thoracic region it is called synspondylism [43]. Klippel feil syndrome is
defined as the congenital fusion of two or more cervical vertebrae and is a
result of faulty segmentation, along the axis of the developing embryo (sclerotomes
of somites) [2] from the 2nd-8th week of gestation [3].
This disease is characterized by a classical triad of three clinical
manifestations, viz., low hairline,
short neck (brevicollis) and restriction of head and neck movements, originally
reported by Klippel and Feil and it also has many other congenital
malformations [4].
Patients often suffer neurological symptoms that may
develop spontaneously or any incidents that involve trauma [5]. The fusion of
two cervical vertebras can be congenital or acquired [6]. The surgical fusion
of two vertebrae is known as spondylodesis or spondylosyndesis, whereas
acquired fusion can be a result of other diseases like juvenile rheumatoid
arthritis, tuberculosis, and, or trauma [6].
KLIPPEL FEIL SYNDROME:
Klippel-Feil syndrome was first described by Maurice
Klippel and Andre Feil in 1912 [51]. This disease is of autosomal dominant
inheritance type [7]. It may also be caused due to fetal alcohol syndrome
(FAS)[54] As seen, in the introduction, this disease was reported by klippel
and feil, and was further classified into three types, Type 1, Type 2, Type 3. In
type 1, The patient has numerous fused vertebrae, with a possibility of upper
thoracic vertebral synostosis. Type 2 on the other hand is fusion of one or two
cervical vertebrae along with other cervical spinal abnormalities. Type 3
involves the fusion of cervical vertebrae with concomitant fusion of thoracic
or lumbar vertebra. Type 2 is very common [8] and C2-C3 fusion is the most
common site, with an incidence of 0.4-0.7% without any predisposition to the
sex [49]. The incidence observed is 1:40,000 to 1:42,000 births [36] of which
60% is in females.
Figure 1- Depicting Klippel-Feil
syndrome[55]
Associated Abnormalities:
Neurovascular Disorders:
Spinal cord injury,
spondylosis, stenosis:
Patients with this disorder have osseous fusions of
their cervical vertebra from birth [9]. They are more predisposed to cervical
cord injury after a minor fall or any incident of trauma, owing to the altered
mechanical properties of their spine [10-18].
The congenital fusions alter the way in which
decelerating and rotatory forces get transmitted through the cervical region of
the vertebral column, increasing the chances of spinal cord injury in trauma [13,15-18].
There are a variety of mechanisms by which these Klippel-Feil syndrome patients
have manifold chances of spinal cord trauma [9]. The probability of occurrence
of spondylotic and discogenic changes at the junctional segments is increased
due to the high biomechanical stress because the segments of vertebra which are
close to the fused part of the vertebra, that are functional and motile, will
become hypermobile [12-15,18,19] to compensate for lack of movement at the
fused areas. Other common consequences are Discal tear, rupture of transverse
ligament, and fracture of odontoid process.
This spondylosis (stiffening of spine) may cause
Cervical spine stenosis (narrowing of spinal column), that subsequently, leads
to spinal cord injury after minor trauma [15,20].
Upper fused cervical vertebra lead to laxity of
ligaments between the occiput and atlas causing brainstem/cord compressions and
associated neurological symptoms [44].
Hemivertebra:
It is a rare congenital spinal anomaly, where only one
half of the body of the vertebra will develop, resulting in deformations of the
bone like kyphosis, scoliosis or lordosis. Excessive curvature of spine in
lower back [49].
Spinal cord contusion:
Cases of spastic quadriparesis along with inverted
vertebral arteries have been reported [47]. Most of the neurological disorders
happen due to chronic compression of cervical spinal cord, pons, medulla and
stretching of cranial nerves. And sudden movements of the neck or minor falls may
lead to basilar artery insufficiency and syncope [48].
Posterior fossa dermoid cysts
[25]:
It’s usually a non-tender benign hairless hump (consisting
of sebaceous material, hair and epithelial debris [50] present in the occipital
region, with symptoms of epistaxis, frontal headaches, ruptures of the cysts
may cause aseptic meningitis. The KFS occurs after development of neuraxis. The
failure of cleavage of ectoderm from neurectoderm, owing to dermal inclusions
into the closing neural tube [26]. About 18 cases of this rare association have
been reported until now. Early diagnosis is important to prevent other
repercussions like neural compression, cyst rupture and staphylococcal
meningitis [50]. Overdistension of neural tube causing distortion of somites,
reduced expression of Hox or Pax genes ( highly conserved DNA
sequences-controlling development of inter-vertebral discs) [27].
Mechanical basis: While the cephalic and cervical
brain flexures are being formed, a short cervical spine or a reduction or fusion
of the somites may alter the tissue tension which may again cause dermal
inclusion [28].
Chiari 1 Malformation:
Otherwise known as tonsillar herniation, It is a
dysraphic (defective fusion of neural tube) congenital disorder, commonly seen
in association with klippel feil syndrome, and other malformations of the same
kind, including syringomyelia (fluid filled cavity or cyst within spinal cord) and
tethered cord(occult spinal dysraphism) [29,30]. This disorder can lead to
sudden and unexpected death.
Chances of tension pneumocephalus, followed by
compression of surrounding structures after posterior fossa surgery is a
well-known fact, though uncommon. Posterior fossa pneumocephalus can cause
immediate cardiac arrest in post-operative period [31].
Agenesis of corpus callosum,
spina bifida (meningocele).
Documented CNS disorders occurring with Klippel-feil
Syndrome include Agenesis of corpus callosum [50] (congenital defect with
complete or partial absence of corpus callosum) and meningocele which occurs
when the outer part of the vertebrae haven’t closed completely and though the
spinal cord isn’t damaged, the meninges are, and they protrude out through the
opening (bulging)
Orofacial Abnormalities:
Commonly associated with type 2 KFS, They exhibit a smaller
lower third of face, and facial asymmetry, and are commonly found to have other
dental implications [45]. Cases have been reported with midline cleft of
anterior hard palatal fistula or even cleft lip, multiple carious teeth and
hence root stumps, ocular hypertelorism, short forehead, broad and flat nasal
bridge, and prognathism [46]. There is hearing loss in 30% of the cases [52].
Wilderwanck syndrome:
cervico-oculo (Duane retraction syndrome) acoustic
(hearing difficulty) anomaly.
Duane Retraction Syndrome:
It has been reported that 30% of the patients with DRS
syndrome (Duane Retraction Syndrome- It is a congenital and non-progressive
strabismus syndrome) are also commonly affected with some other systemic
conditions that include- Klippel-Feil syndrome [23].
Agenesis of Organs:
Agenesis of gall bladder,
lungs with allergic rhinitis and asthma [24, 32]
An opaque hemithorax, led to diagnosis of KFS
associated with agenesis of gall bladder and lungs or pulmonary hypoplasia or lobar agenesis, in
a patient with a history of wheezing dyspnea, which was diagnosed as asthma and
allergic rhinitis. The other associated symptoms observed are low lying
posterior hairline, short neck and webbing, painless restriction of neck
movements, more pronounced on one side, walking with a limp on the opposite
side, rib hump posteriorly on a side, shoulder appeared high on a side, and
chest appeared prominent on one side. Pectus Excavatum observed (hollowed
chest), along with chest asymmetry. Bone impinging on the brain stem, may lead
to intrinsic deformities of the nervous system, and any problems of the Cerebrospinal fluid may affect
respiratory function [11].
Pulmonary complications are rare in association with
KFS (reported only 4 times before), which may be due to decreased blood flow
due to absence of the pulmonary vasculature or a reduction in intra thoracic
space as a result of congenital kyphoscoliosis (abnormal curvature of spine),
which may in turn be misdiagnosed as non-resolving pneumonia.
Mayer-Rokitansky-Kuster-Hauser
(MRKH) syndrome:
Occurs in 1 in 4000-5000 females [39,40]. In this
syndrome the patient has a uterine and vaginal aplasia or hypoplasia (upper 2/3rd
of vagina) and primary amenorrhoea but functional ovaries [41]. Klippel-Feil syndrome is associated with the
third type of this disorder the MURCS type, that involves Utero-vaginal aplasia
or hypoplasia, renal (renal agenesis on one side or both [42], cardiac and bone (KFS and scoliosis)
malformations.
Cardiac Anomalies:
It is a well- known fact that women with Klippel-Feil
syndrome are predisposed to cardiac anomalies [33] like-Lown-Ganong-Levine
syndrome which is a pre excitation syndrome characterized by paroxysms of
tachycardia. This syndrome can also lead to cervicogenic angina due to the
irritation of the cervical nerve root, mimicking true cardiogenic angina. This
occurs due to the narrowing down of the intervertebral foraminae, causing
compression of the contents passing through it, leading to vascular and
neurological symptoms [44]. It can cause complete heart block [55].
Associated Musculoskeletal
Anomalies:
Bicipital Rib: [34]
0.3% of incidence of fused first and second rib. It is
an unusual anatomical phenomenon due to the fusion of shafts of two ribs, into
one body, the fused ribs (with respect to the first rib, it can be fused with a
cervical rib or with the second rib (more common). The cervical rib may fuse
with the vertebral end of the first rib, or due to the rudimentary first rib, that
fuses with the second rib [35]. There are 22 syndromes in which rib anomalies
are a constant component: Klippel-Feil syndrome, Poland and Gorlin syndrome (basal
cell naevus syndrome), Jarco-Levin syndrome.
Sprengel deformity[46]-elevated scapula.
Pterygium like effect [46]-flaring of trapezius muscle.
Respiratory Difficulty:
Observations made are usually intercoastal and
substernal recessions, bilateral crepitations. In a neonate, the reflexes were
sluggish on CNS examination [37]. The thoracic vertebrae, the intervertebral
disc and the ribs help to maintain length and therefore volume of the thorax,
so any osseous fusion of these entities or absence of the disc will lead to
reduce in thoracic volume and causes respiratory distress [6].
Embryological Basis:
Vertebrae and the intervertebral discs are one of the
chief manifestations of body segmentation or metamerism [43]. It is seen due to
faulty segmentation (occurs during organogenesis) along the axis of the
developing embryo in the 3rd to 8th week of gestation [36].
It has been hypothesized that decreased local blood supply in this period would
lead to improper segmentation [44]. The vertebral column is derived from the
sclerotomes of somites. In the 4th week, they arise in the cervical
region, and followed by the migration of the sclerotomic cells to the vertebral
centrum, costal processes and neural processes after losing adherence in the 5th
week. Each of the thoracic neural processes will lead to the formation of a
cartilagenous pedicle, lamina and transverse process. For both the neural processes
and the centrum, ossification centres arise, and spread up and down in the
column, from T10 and L1 and C2 and T1 [6].
Treatment and Management:
Management of patients with spinal cord injury depends
on the intensity of loss of stability and function, presence or absence of a
spinal cord compression, and its associated neurological disorders [18,21,22] Since
KFS has such a wide spectrum of co morbidities, a better treatment option would
be to treat the associated disorders [24]. MRI (Magnetic Resonance Imaging) of
the cervical spine in extension and flexion, must be done, identify any other
deformity, and antero-posterior and
lateral radiographs must be taken while extension and flexion to analyse the
severity and the location of hypermobility [37]. Physical therapy administered
may also be beneficial [38]. Patients with Klippel-feil anomaly pose a
challenge to the anaesthetist due to the management of difficult airway, and
the most effective way will be fibreoptic intubation through a laryngeal mask. [53,48]
Patients with KFS and posterior fossa dermoids should be carefully scrutinized
with imaging, as the cyst and the sinus tract must be surgically removed [25] A
rib anomaly is associated with a systemic disease and in the case of fusion of
first and second rib, there is a vascular compromise and needs a surgical
intervention[34]. For patients with MRKHS, vaginoplasty is advised after the
surgical treatment to correct the renal and uterine abnormalities [42].
CONCLUSION:
Fused cervical vertebrae have many embryological and
clinical implications as described above, owing to which, these anomalies of
the cervical region are of interest to orthopedists, anatomists, neurologists,
neurosurgeons and even orthodontists. Here the fused vertebrae appear structurally
and functionally as one [49]. Due to the diversified co-morbidities it is
important for a physician to have proper knowledge about the manifestations for
proper diagnosis and management.
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