Summary Klippel-Feil Syndrome (KFS) is a rare congenital condition caused by failure of normal segmentation or formation of cervical somites during embryological development that leads to abnormalities in multiple cervical segments. Diagnosis is made from physical examination, medical history and imaging findings including congenital fusion of 2 or more cervical vertebrae. Treatment is usually observation with restriction of contact sports if the anomaly extends proximal to C2. Surgical management is indicated in the presence of myelopathy, basilar invagination, or atlantoaxial instability. Epidemiology Incidence historically regarded as extremely rare 1 in 40,000 live births (0.0025%) recent literature suggests higher prevalence in asymptomatic individuals 1 in 172 (0.58%) to 1 in 83 (1.20%) Demographics 60-70% of cases are female Etiology Pathophysiology mechanism due to failure of normal segmentation or formation of cervical somites at 3-8 weeks' gestation affected levels most common fusion levels are C2-C3 and C5-C6 Genetics three major inheritance patterns sporadic (most common) often presents as isolated cervical fusion autosomal dominant GDF6 gene (chromosome 8) GDF3 gene (chromosome 12) autosomal recessive MEOX1 gene (chromosome 17) most common SGM1 gene (Chr 8) Notch and Pax genes Associated conditions orthopedic conditions congenital scoliosis Sprengel's deformity (30%) Wildervanck syndrome (cervico-ocular-acoustic dysplasia) triad consists of: Klippel-Feil syndrome congenital ossicular anomalies; usually diffuse ossicular ankylosis and sensorineural deafness Duane syndrome (ocular motility disturbance due to fibrosis of extraocular muscles medical conditions & comorbidities renal disease (aplasia in 33%) auditory issues (deafness in 30%) congenital heart disease/cardiovascular (15-30%) most commonly ventricular septal defects (VSD) brainstem abnormalities/basilar invagination congenital cervical stenosis MRI to rule out intraspinal cord abnormalities atlantoaxial instability (~50%) adjacent level disease (100%) degeneration of adjacent segments of cervical spine that has not fused is common due to increased stress Classification KFS classification KFS classification Type I Extensive fusion of most or all of the cervical spine Sporadic mutation Type II Fusion or only 1 or 2 vertebrae in the cervical spine Autosomal dominant Type III Fusion exists in part of the thoracic and/or lumbar spine, in addition to Type I or Type II KFS Autosomal recessive Despite this original classification, none is widely accepted extent and locations of fusions is important fusions above C3 more likely to be symptomatic and require abstaining from contact sports fusions below C3 less likely to be symptomatic and most likely to have a normal life span Samartzis classification carries prognostic value Samartzis classification (2006) Type I Single-level congenital fusion of cervical segment symptoms tend to be more axial Type II Multiple, noncontiguous congenitally fused segments tend to develop peripheral myelopathy or radiculopathy Type III Multiple, contiguous congenitally fused segments in the cervical region tend to develop peripheral myelopathy or radiculopathy Clarke classification comprehensive classification system that addresses genotypic and phenotypic heterogeneity Clarke Classification (1998) Class Vertebral Fusions Inheritance Possible Anomalies Overlap with other classifications KF1 Only class with C1 fusion C1 fusion not dominant Variable expression of other fusions Fusions radiologically visible at birth Autosomal Recessive Very short neck, heart, urogenital, craniofacial, hearing, limb, digital, ocular defectsVariable expression Variable expression Types I, II, III (KFS Classification) Recessive (Gunderson) KF2 C2-3 fusion dominant C2-3 fusion most rostral fusion Cervical, thoracic and lumbar fusion show variable expression within a family Fusions apparent postnatally Autosomal Dominant Includes SGM1 gene mutation Craniofacial, hearing, otolaryngeal, skeletal and limb defects, etc Variable expression Types I, II, III (KFS Classification) C2-3 dominant (Gunderson) KF3 Isolated cervical fusions, includes single fusions at variable positions Any cervical fusion except C1-2Includes single C5±6 fusion Includes single C5-6 fusion Autosomal Recessive or reduced penetrance Craniofacial Facial dysmorphology Variable expression Type II (K & F) C5-6 recessive (Gunderson) KF4 Fusion of cervical vertebrae Limited data available X-linked Predominantly females Hearing and ocular anomalies - abducens palsy with retractio bulbi Heart defects possible Commonly referred to as Wildervanck syndrome (includes Duane's syndrome) Presentation Symptoms stiff neck neck/back pain mean age of onset 16 years mean age of symptom worsening 28 years Physical exam inspection classic triad (seen in fewer than 50%) low posterior hairline short webbed neck limited cervical ROM other findings high scapula (Sprengel Deformity) 6.4% to 16.7% of cases jaw anomalies partial loss of hearing torticollis congenital scoliosis 53.5% of cases myelopathy KFS patient have higher rates of cervical myelopathy than the general population Imaging Radiographs recommended views AP, lateral, and open-mouth odontoid views whole spine radiograph to look for multiple fused levels (KFS Type III) findings fusion may be craniocervical (occiput to C2), subaxial, or both basilar invagination is seen on lateral view defined as dens elevation above McRae's line atlantoaxial instability is present when the atlanto dens interval (ADI) is >5 mm cervical spinal canal stenosis is seen when spinal cord canal <13 mm degnerative changes degnerative disease of the cervical spine is seen in 100% calcifications calcifications may be seen within the intervertebral space resolution within 6 months is common Ultrasound abdominal ultrasound renal aplasia/agenesis echocardiogram congenital heart conditions most commonly ventricular septal defects CT cervical spine preoperatively delineate bony anatomy and fusion patterns MRI concomitant CNS abnormalities occur in 19% of KFS patients brain brain stem abnormalities basilar invagination cervical spine intraspinal cord abnormalities smaller cross-sectional spinal cords with larger canal diameters at all levels tethered cords diastematomyelia Differential congenital scoliosis postinfection/spine inflammatory disorders Mayer-Rokitansky-Kaster syndrome Sprengel's deformity Treatment Nonoperative observation with ability to participate in contact/collision sports indications asymptomatic patients with fusions of 1-2 disc spaces below C3 Samartzis type II lesion at C3 and below with full range of cervical spine motion and lack of instability and spondylosis observation and abstain from contact/collision sports modalities no standardized guidelines for sports participation counseling important to avoid activities that place the neck at high risk of injury contact sports, gymnastics, football, wrestling, trampoline, etc. absolute contraindications to sports participation asymptomatic patients with fusion involving C2 most common presentation long fusions multilevel fusions any limitation in cervical motion Samartzis type I and II lesions with limited range of motion, C2 involvement, instability or spondylosis, and occipitocervical anomalies any patient undergoing surgical management of KFS relative contraindications to sports participation Samartzis type II lesion with known previous episode of transient quadriplegia Operative surgical decompression and fusion indications basilar invagination chronic pain myelopathy associated atlantoaxial instability adjacent level disease if symptomatic progressive scoliosis deformity 82% of KFS patients with congenital scoliosis will require surgical correction phenotypes associated with higher rates of surgical intervention subaxial cervical spine fusions and thoracic spine anomalies, associated with thoracolumbar and sacral surgical interventions axial spine anomalies, which correlated with subluxations and cervical spinal fusion Chiari malformations and associated neurosurgical procedures thoracic spine anomalies, scoliosis, and sacral agenesis Complications Cervical spinal cord injury usually associated with participation in high-impact contact sports theory that smaller diameter spinal cords may create an increased risk for cervical spinal cord injury