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Pathology of Cervical Spine Anomalies in Children

This page was last updated on April 8th, 2024


Down syndrome (trisomy 21)

  • Atlantooccipital joint: The atlantooccipital joint in patients with Down syndrome has a “rocker-bottom” configuration, with flat, wide occipital condyles and flat C1 articular surfaces (6). It is thought this anatomical abnormality contributes greatly to atlantooccipital hypermobility and sometimes instability.
  • Atlantoaxial hypermobility: Atlantoaxial hypermobility due to ligamentous laxity may be severe enough to cause atlantoaxial instability. The exact amount of hypermobility necessary to cause instability is unknown, although it is known that C1-2 hypermobility rarely worsens after about 10 years of age (22).
  • Anatomical anomalies of the atlas: The atlas has many anatomical variants in Down syndrome, although an absent or split posterior arch or a bifid arch (leading to two hemi-rings) are the two most common. Odontoid abnormalities such as os odontoideum or hypoplastic dens may be present. 

Down syndrome, extension x-ray: Note posterior translation of the occiput on C1.

Down syndrome, flexion x-ray: Note anterior translation of occiput on C1.



  • Foramen magnum: Skull films and CT demonstrate a large skull with a narrow foramen magnum, with a relatively small skull base. A narrow foramen magnum may lead to myelopathy (11, 26).
  • Vertebral body anomalies: The vertebral bodies are short and flattened with relatively large intervertebral disk height. The spinal canal may be narrowed and can contribute to myelopathy as well.

Klippel-Feil syndrome and Klippel-Feil variant

  • Clinical triad: Klippel-Feil syndrome is classically identified as the clinical triad of low-lying hairline, short neck, and cervical fusion abnormalities.
  • Variant: Cervical fusion abnormalities alone are known as Klippel-Feil variant.
  • Associated anomalies: Associated abnormalities include scoliosis, rib abnormalities, Sprengel deformity, synkinesia, and genitourinary and cardiovascular disorders (12, 13).
  • Classification: Tracy et al. proposed a system for classifying cases (25). KF1 refers to fusions at C1 with or without caudal fusions. KF2 refers to fusions no higher than C2-3. KF2 types are autosomal dominant with 100% penetrance. KF3 refers to fusions that are no higher than C2-3, but unlike KF2 these are inherited in an autosomal recessive fashion. KF4 are cervical fusions that are associated with hearing loss and Duane anomaly (Wildervanck syndrome).


  • Scalloping and kyphosis: Scalloping of the vertebral column is common but does not necessarily cause cervical instability. Kyphotic cervical abnormalities may occur because of a combination of poor bone quality, scalloping, and ligamentous insufficiency.

Os odontoideum

  • Disjunction of the odontoid-C1 complex from C2: Os odontoideum results in the functional disconnection of the odontoid-C1 complex and the body of C2. It is assumed that if atlantoaxial instability is not present, then the inflammatory or fibrous tissue present at the base of odontoid rarely, if ever, stabilizes the joint. There are two types of os odontoideum: dystopic and orthotopic.
  • Dystopic os odontoideum: The os fragment is functionally connected to the basion.
  • Orthotopic os odontoideum: The os fragment moves with the anterior arch of the atlas. This type is by far the most common.

Common skeletal dysplasias

  • Morquio syndrome: Morquio syndrome is a mucopolysaccharide storage disease that results in the accumulation of keratin sulfate.
  • Osteogenesis imperfecta, types III and IV:  Osteogenesis imperfecta results in defective connective tissue, without the ability to make it, usually because of a deficiency of type 1 collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure.

Molecular/Genetic Pathology

Down syndrome

  • Chromosome 21: Down syndrome is caused by an extra copy of chromosome 21.


  • FGFR3 mutation: Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3), which causes an abnormality of cartilage formation.

Klippel-Feil syndrome and Klippel-Feil variant

  • PAX gene: Pedigree analysis has identified a human genetic locus for the disease. Mouse models suggest members of the PAX gene family and Notch signaling pathway as possible etiologic candidates.
  • Klippel-Feil 4 X-linked: This type is inherited in an X-linked dominant fashion.


  • Chromosome 17: NF1 is caused by a mutation of a gene on the long arm of chromosome 17. The gene encodes the protein neurofibromin, which plays a role in cell signaling.

Os odontoideum

  • None known: No known genetic abnormality exists for os odontoideum.

Common skeletal dysplasias

  •  Morquio syndrome (mucopolysaccharidosis IV): The syndrome is autosomal recessive. Type A (severe) and type B (mild) are recognized by the enzymes involved.
  • Spondyloepiphyseal dysplasia: This condition is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. It is inherited as an autosomal dominant.
  • Diastrophic dwarfism: This is an autosomal recessive condition that is due to mutations in the SLC26A2 gene with an incidence of 1 in 100,000.
  • Osteogenesis imperfecta, types III and IV: These conditions are autosomal dominant.