Klippel-Feil syndrome

Author(s): Yuxi Chen, MD, Jared Ruben Levin, MD

Originally published:09/20/2014

Last updated:02/15/2018

1. DISEASE/DISORDER:

Definition

Klippel-Feil syndrome (KFS) is a clinical and radiologic entity with congenital fusion of two or more of the cervical vertebrae or brevicollis anomaly.1,2

  • It is the most common congenital malformation of the cervical spine.
  • Short neck, low posterior hairline, and limitation of neck mobility are considered the “classic triad” of findings.
  • Fewer than 50% patients have the classic triad, although the prevalence of each finding increases in more involved cases.3

Etiology

Variable clinical presentation complicates identification of a definite cause. It may result from mutations or aberrant expressions of genes regulating segmentation and resegmentation of sclerotome (results from ventral subdivision of mature somite and consists of mesenchymal cells, which form the adult vertebrae) during the third to eighth week of gestation.1

  • Mutations in at least three genes have been linked to KFS: GDF6, GDF3 and MEOX1, the mode of inheritance varies by type.
  • Paracentric inversion of chromosome 8q may link to KFS and vocal cord defect from pedigree analysis,
  • Mutation in fibroblast growth factor receptor 3 gene: autosomal dominant, coronal synostosis, Sprengel, dysmorphic ribs, and vertebrae.

Epidemiology including risk factors and primary prevention

The exact incidence and prevalence are unknown because of unavailability of population screening studies. Incidence is estimated at 1 in 40,000 to 42,000 births.4, 5 Predominance of women (3:2 or 60%-70%) has been reported.

Risk factors and primary prevention are unknown.

Patho-anatomy/physiology

  • The hallmark of KFS is improper segmentation of cervical vertebrae resulting in abnormal fusion with or without associated manifestations.
    Involvement of thoracic and lumbar vertebrae.

    • Increased risk of degenerative and traumatic changes in adjacent level disks because of altered spinal kinematics.6
  • Normative range of motion, intersegmental hypermobility of upper cervical, lower cervical, or combination of both.
  • The original Feil classification, is often cited and listed as the following 3 types 7:
    • Type I: fusion of cervical and upper thoracic vertebrae
    • Type II: fusion of only 1 or 2 pairs of cervical vertebrae
    • Type III: cervical fusion in combination with lower thoracic or lumbar fusions
  • Samartzis radiographic classification of congenital spinal fusion4
    • Type I: Single cervical
    • Type II: Multiple noncontiguous segments
    • Type III: Multiple contiguous cervical fusions
  • Classificationbased on spinal kinematics 1
    • I: C1 fusion with/without more caudal fusions, autosomal recessive
    • II: most rostral C1-3 fusion, autosomal dominant, 100% penetrance
    • III: isolated fusion caudal to C1-3 autosomal recessive/dominant reduced penetrance
    • IV: Wildervanck syndrome, X-linked dominant, hemizygous lethality

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

  • 50% pediatric patients are asymptomatic.4
  • Axial symptoms (neck pain, headache, neck stiffness) are predominant in symptomatic patients.
  • C1-2 or extensive fusions present early.
  • Lower-level fusions present in second or third decades.
  • Axial symptoms and myelopathies occur in early and later adolescence, respectively, and are pronounced in adulthood.4,7
  • Risk of radiculopathic or myelopathic symptoms may be greatest between Samartzis types III and II.4

As patients age, degenerative changes throughout the cervical spine can account for the following conditions4:

  • Spinal canal stenosis
  • Fracture
  • Spondylosis
  • Disk degeneration
  • Disk herniation
  • Osteophytes

Specific secondary or associated conditions and complications

  • Congenital scoliosis (most common; 60%): intervention with curves over 55°
  • Sprengel deformity (20%-35%)
  • Cervical spina bifida, basilar invagination, Chiari malformation causing brain stem abnormalities, myelopathies, radiculopathies, weakness, numbness. 6
  • Torticollis, facial asymmetries
  • Distal longitudinal upper limb deformities with bilateral/unilateral, cosmetic, functional implications
  • Deafness (30%): cervico-oculo-acoustic dysplasia
  • Mandibular malformations
  • Cleft palate
  • Cardiovascular (14%): ventricular septal defect (most common), atrial septal defect, coarctation, anomalous pulmonary veins
  • Genitourinary (60%): renal and ureteral agenesis, hydronephrosis, absent/malrotated kidneys, absent vagina, ovaries, uterus, absent/hypoplastic testes
  • Synkinesis/mirror movements of hands interfering with fine motor function1,2,4, 8,
    • Wildervanck, Goldenhar, Mayer-Rokitansky-Kuster-Hauser syndromes7

2. ESSENTIALS OF ASSESSMENT

History

Because of heterogeneity of KFS, comprehensive evaluation is required.

  • Clinical presentation varied
  • Often asymptomatic and an incidental finding
  • Can be diagnosed throughout life

Detailed history includes the following:

  • Decreased neck range of motion.
  • Presence of neck and radicular pain from degenerative changes or hypermobility arising at the interspace between fused segments.
  • Neurologic symptoms (numbness, paresthesia, spasticity, paralysis) with or without mild trauma.
  • Anomalies in other organ systems with the same embryologic development as the cervical spine, including hearing loss and cardiovascular, renal, and reproductive system anomalies.
  • Family history with autosomal dominant and recessive inheritance pattern.

Physical examination

Head and neck

  • Classic triad decreased neck rotation, lateral bending, flexion, and extension (<50%)
  • Torticollis or neck webbing (20%) and cervical scoliosis (50%)8, 9
  • Evaluate for facial/mandibular asymmetry (less common)

Musculoskeletal

  • Thoracic lumbar scoliosis (most common)
  • Range of motion of shoulder joint and scapula elevation and palpate for omovertebral bone
  • Examine chest wall for rib anomalies (33%)1
  • Upper extremity congenital deficiency (less common)

Neurologic

  • Cranial nerves: hearing loss
  • Signs of central nervous system pathology, myelopathy, or radiculopathy
  • Presence of synkinesis

Cardiovascular

  • Cardiac murmur, edema, or cyanosis

Renal and reproductive

  • Nephrology and urology consultation and exam

Functional assessment

  • Assess neurologic deficits affecting gross and fine motor functions and gait balance.
  • Assess communication function if patient has hearing loss or vocal cord defect.
  • Evaluate upper extremity function, including self-care skills in limb deficiencies.

Laboratory studies

None specific for KFS.

Imaging

  • High-quality spinal radiographs to evaluate the nature and extent of fusion1
  • Initial study
    • Plain radiography of the cervical spine anteroposterior, lateral, and open-mouth odontoid views to identify congenital fusion, basilar invagination, or cervical stenosis
  • Dynamic study
    • Flexion and extension views of cervical spine to evaluate stability of the atlantooccipital, atlantoaxial, and subaxial joints
    • Imaging of cartilaginous spine can be difficult to interpret
    • Pseudosubluxation of C2 on C3 and C3 on C4 is physiologically normative in 20% to 46% of children under 7 years of age10
    • Imaging of the thoracic and lumbar spine for scoliosis
  • Magnetic resonance imaging (MRI) of brain and cervical spine
    • For brain, brainstem, and spinal cord/central nervous system lesions, syrinx, tethered cord, diastematomyelia, and Chiari malformation (3%-5% of patients with Chiari malformation are diagnosed with KFS)11
    • Flexion-extension MRI may reveal cord compression and spinal stenosis
  • Computed tomography
    • Defines bony structure but exposes child to radiation
  • Renal ultrasonography or intravenous pyelogram to evaluate for anomalies
  • Echocardiogram

Supplemental assessment tools

Audiology for hearing test

Early predictions of outcomes

  • Patients with atlantoaxial fusions or with extensive fusions present at an earlier age.1
  • Hypermobility of the upper cervical spine presents the greatest risk for neurologic compromise, whereas hypermobility of the lower cervical spine causes the greatest risk for degenerative disk disease.8
  • The classification system by Samartzis is useful in predicting outcomes.7
  • KFS cervical fusion patterns are largely manifest as type II with multiple noncontiguously fused segments and are largely asymptomatic in the pediatric population.
  • Type I patients with a single fused segment have predominantly axial symptoms of neck/headache, neck pain, and neck stiffness.
  • Type III with multiple contiguously fused segments and type II patients are associated with a higher incidence and risk of developing radiculopathy or myelopathy as subsequently noted.

Environmental

Inquire about the patient’s home, school, or work environment to determine appropriate adaptive devices and equipment to allow easy reach and prevent falls.  Environmental and activity modifications may be needed to accommodate patient’s deformity, such as to avoid contact sports and neck hyperextension.

Social role and social support system

Inquire about patient’s family, home, and social situation that may impact treatment options.

Professional Issues

Although affected patients have cervical abnormality at birth, KFS usually is diagnosed at a later age when neurologic,  biomechanical, or other system problems occur. Genetic advances may help reveal the causes and assist in early diagnosis, prevention, and treatment in the future.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

There are currently no consensus rehabilitation protocols for KFS.

At different disease stages

Most cases are treated non-operatively unless there is cervical instability, acute neurologic deficit, or impending or chronic neurologic compromise.

Nonsurgical

  • For axial symptoms and radiculopathy, use soft tissue massage and therapeutic treatment, including modalities and medications. 7 Avoid spinal manipulation.
  • For transient quadriparesis, soft cervical collars and bracing are recommended with varying degrees of success. For patients with symptomatic basilar invagination, cervical traction with a halo has shown clinical and radiologic benefits prior to a surgical fusion procedure.12For patients with central cord syndrome, conservative treatment is controversial, but cervical traction has demonstrated relief of symptoms in patients under 50 years of age.13
  • Therapy services vary. Aerobic and aquatic exercise are preferred. Postural exercises and strengthening of neck, shoulder, and periscapular musculature arerecommended in most patients. Range of motion should be addressed in cases of torticollis and Sprengel deformity. Breathing exercises are recommended for patients with scoliosis.14Occupational therapy is recommended for synkinesia.8Other options include prosthetic training for limb deficiencies, speech therapy for vocal cord impairment, and a home exercise and stretching program.
  • Noncontact sports and aquatic exercises are the preferred recreational activity. Avoid contact sports, exercises with falls or stressing the cervical spine, tumbling, and jumping.
  • Sports participation guidelines are not standardized. Cardiac and renal comorbidities may preclude participation. Recommendations, however, have been documented15as follows:
    • Type I lesion: absolute contraindication
    • Type II lesion with fusion of 1 or 2 interspaces with limited range of motion, occipitocervical anomalies, C2 involvement, instability, or spondylosis: absolute contraindication
    • Type II lesion with previous episode of transient quadriplegia: relative contraindication
    • Type II lesion C3 and below with full cervical range of motion and absence of instability and spondylosis: can participate

Surgical

  • Neurosurgery with spinal decompression, untethering of the spinal cord, and lysis of adhesions with electrophysiologic monitoring. Postoperatively, patients wear a halo vest for approximately 3 months, followed by a soft cervical collar for 3 months.16
  • Arnold-Chiari malformation and myelomeningocele repair. Orthopedic surgery may be consulted for scoliosis repair and spinal stenosis decompression. Cosmetic scapuloplasty for Sprengel deformity.17
  • Oral and maxillofacial surgery for cleft palate and associated craniofacial deformities.18

Otolaryngology may be necessary for hearing devices or cochlear implants.19

Coordination of care

  1. Multidisciplinary care coordinated by physiatry.
  2. Rehabilitation services include physical, occupational, and speech therapy.
  3. Orthotics and assistive devices can be used for patients with scoliosis and functional limitations.
  4. Prosthesis may be used for congenital limb deficiency.
  5. Surgical specialists include neurosurgery, orthopedics, otolaryngology, and oral and maxillofacial surgery.
  6. Medical specialists include neurology, cardiology, nephrology, and genetics.

Patient & family education

  1. Falls prevention and modification of work/leisure activities.
  2. Home modification with removal of obstacles presenting a fall risk and repositioning of overhead objects in patients with Sprengel deformity.
  3. Environmental awareness with conductive hearing loss.
  4. Management of patient and family expectations regarding activity levels, especially after new onset quadriparesis.

Emerging/unique interventions

There are no standardized measurement scales for outcomes in KFS. Outcome measures should be based on treatment of specific symptoms.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Practitioners should maintain a high index of suspicion for signs and symptoms of new or recurrent neurologic decline, including radiculopathy, myelopathy, quadriparesis, or sleep apnea.19, 20
  • Early intervention with therapy and modification of activities may reduce the risk of subsequent trauma and degenerative disk changes.
  • Because of associated craniofacial and cervical spine abnormalities, care must be taken during intubation to avoid neurologic injury.16 Also, anesthesia risk may increased if patient has underlying heart defect.
  • Juvenile rheumatoid arthritis can mimic KFS with similar cervical spine anomalies, although clinic examination, including serology, easily distinguishes the 2 conditions.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Not available at this time.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Not available at this time.

REFERENCES

  1. Thomsen MN, Schneider U, Weber M, Johannisson R, Niethard FU. Scoliosis and congenital anomalies associated with Klippel-Feil syndrome types I-III.Spine (Phila Pa 1976). 1997;22(4):396-401.
  2. Pizzutillo PD, Woods M, Nicholson L, MacEwen GD. Risk factors in Klippel-Feil syndrome.Spine (Phila Pa 1976). 1994;19(18):2110-2116.
  3. Samartzis D, Kalluri P, Herman J, Lubicky JP, & Shen FH. (2016). “Clinical triad” findings in pediatric Klippel-Feil patients. Scoliosis and Spinal Disorders, 11(1).
  4. Samartzis D, Herman J, Lubicky J, Shen FH. Classification of congenitally fused cervical patterns in Klippel-Feil patients. Spine (Phila Pa 1976). 2006;31(21):E798-804.
  5. Nouri A, Martin AR, Tetreault L, Nater A, Kato S, Nakashima H, . . . Fehlings MG. (2017). MRI Analysis of the Combined Prospectively Collected AOSpine North America and International Data. Spine, 42(14),
  6. Nouri A, Martin A R, Lange SF, Kotter MRN, Mikulis DJ, Fehlings MG. Congenital Cervical Fusion as a Risk Factor for Development of Degenerative Cervical Myelopathy. World Neurosurg. 2017 Apr;100:531-539.
  7. Tracy MR, Dormans JP, Kusumi K. Klippel-Feil syndrome: clinical features and current understanding of etiology.Clinic Orthop Relat Res.2004;(424):183-190.
  8. Klimo P Jr, Rao G, Brockmeyer D. Congenital anomalies of the cervical spine.Neurosurg Clin N Am.2007;18(3):461-478.
  9. Samartzis D, Kalluri P, Herman J, Lubicky JP, Shen FH. Cervical scoliosis in the Klippel-Feil patient.Spine (Phila Pa 1976). 2011;36(23):E1501-E1508.
  10. Kim HJ. Cervical spine anomalies in children and adolescents.Curr Opin Pediatr. 2013;25(1):72-77.
  11. Markunas CA, Soldano K, Dunlap K, et al. Stratified whole genome linkage analysis of Chiari Type I malformation implicates known Klippel-Feil syndrome genes as putative disease candidates.PLoS One. 2013;8(4):e61521.
  12. Dokai T, Nagashima H, Nanjo Y, Tanida A, Teshima R. Posterior occipitocervical fixation under skull-femoral traction for the treatment of basilar impression in a child with Klippel-Feil syndrome.J Bone Joint Surg Br.2011;93(11):1571-1574.
  13. Matsumoto K, Wakahara K, Sumi H, Shimizu K. Central cord syndrome in patients with Klippel-Feil syndrome resulting from winter sports: report of 3 cases. Am J Sports Med.2006;34(10):1685-1689.
  14. Mittal N, Majumdar R, Chauhan S, et al. Sprengel’s deformity: association with musculoskeletal dysfunctions and tethered cord syndrome.BMJ Case Rep.2013 Apr 18;2013.
  15. Holmes FC. Klippel-Feil syndrome in a cheerleader.Clin J Sport Med.2007;17(2):154-156.
  16. Samartzis D, Lubicky JP, Herman J, Kalluri P, Shen FH. Symptomatic cervical disc herniation in a pediatric Klippel-Feil patient: the risk of neural injury associated with extensive congenitally fused vertebrae and a hypermobile segment.Spine (Phila Pa 1976). 2006;31(11):E335-E338.
  17. Singh S, Shakthi Kumar K, Venugopala D, Paul Korath M, Govindan A, Jagadeesan K. Klippel Feil Syndrome.Bombay Hospital Journal. 1999;4(3).
  18. de Lima Mde D, Ortega KL, Araújo LC, Soares MM, de Magalhães MH. Dental team management for a patient with Klippel-Feil syndrome: case report.Spec Care Dentist. 2009;29(6):244-248.
  19. McGaughran JM, Kuna P, Das V. Audiological abnormalities in the Klippel-Feil syndrome.Arch Dis Child.1998;79(4):352-355.
  20. Rosen CL, Novotny EJ, D’Andrea LA, Petty EM. Klippel-Feil sequence and sleep-disordered breathing in two children.Am Rev Respir Dis. 1993;147(1):202-204.

Bibliography

Thomsen M, Krober M, Schneider U, et al. Congenital limb deficiences associated with Klippel-Feil syndrome: a survey of 57 subjects.Acta Orthop Scand.2000;71(5):461-464.

https://rarediseases.info.nih.gov/diseases/10280/klippel-feil-syndrome#ref_9622

Original Version of the Topic

Yuxi Chen, MD, Rani Kathinithamky, MD, David Cancel, MD. Klippel-Feil syndrome. 09/20/2014.

Author Disclosure

Yuxi Chen, MD
Nothing to Disclose

Jared Ruben Levin, MD
Nothing to Disclose

Related Articles