Introduction

The vertebral column consists of 33 bones (7 cervical, 12 thoracic, 5 lumbar, 5 sacral, and one coccyx) that are connected and function together to give structural support to humans as well as protect neurons as they carry information to and from the brain. The embryological development of the vertebrae is complex, but it is vital to understand as errors in development can result in many congenital abnormalities.

Development

Gastrulation is a process in embryonic development in which the two-layered blastula becomes a three-layered gastrula consisting of the endoderm, mesoderm, and ectoderm. The development of the vertebrae begins at this time with the development of the notochord. The mesoderm surrounding the notochord separates into three areas: the paraxial, lateral, and intermediate areas.  The intermediate mesoderm contributes to the urogenital system, while the lateral mesoderm contributes to other organ systems, including the cardiac and pulmonary systems. The paraxial mesoderm then develops into 42 pairs of somites that develop in a craniocaudal direction. Each somite then differentiates into a dermomyotome and a sclerotome. The dermomyotome eventually forms the muscle and dermis of the skin, while the sclerotome becomes the skeleton of the vertebral column.[1]

After separate sclerotome form from each somite, the cells migrate and begin to surround the notochord. Each sclerotome starts to separate into two different clusters of cells: one located cranially and the other caudally. Between each cluster, an intervertebral disc develops. The intervertebral disc consists of a central core known as the nucleus pulposus and an outer ring known as the annulus fibrosis. The nucleus pulposus originates from the notochord, while the annulus fibrosis originates from the sclerotome.[2] The caudally located cluster of one sclerotome then fuses with the cranially located cluster of the adjacent sclerotome creating the vertebral body.[1] As this process is occurring, just dorsal to this, the development of the neural tube (the precursor to the CNS) is occurring. Cells of the sclerotomes eventual migrate around the neural tube and fuse dorsally, creating the vertebral arch that protects the spinal cord.[1]

Ossification of the vertebrae occurs in three primary centers and five secondary centers. One primary center of ossification is in the centrum, and the remaining two are on each side on the neural processes. There are five secondary ossification centers; the tip of the spinous process, the tip of both transverse processes, and the superior and inferior surfaces of the vertebral body.[1]

Molecular Level

Of utmost importance to correct vertebral column development is proper gene expression and cell signaling that allows each vertebra to take the appropriate shape in the anterior-posterior and cranio-caudal direction. One of these genes, known as Hox, is responsible for the proper orientation of the vertebrae in the cranio-caudal direction.[3] The SHH gene is another gene found to play an essential role in anterior-posterior development and ventral neural tube and somite patterning.[4] Many genes have been and continue to be discovered that will further our understanding of this process and potentially how errors in specific genes and their associated signaling pathways could result in common congenital anomalies.

Clinical Significance

As the development of the vertebrae is a complex process and is also vital for the proper development of organs and limbs, many congenital defects correlate with errors in proper vertebral development.

VACTERL 

VACTERL stands for vertebral anomalies (V), anal atresia (A), cardiac malformation (C), tracheoesophageal fistula (TE) with or without esophageal atresia, renal dysplasia (R) and limb abnormalities (L). VACTERL is a purely clinical diagnosis that is made by patients having three or more of the listed anomalies. The most common defect found in VACTERL patients is vertebral anomalies – found to be reported in 60-95% of VACTERL patients. Vertebral anomalies seen include failure of formation and/or segmentation of vertebrae. The exact genetic causes of VACTERL syndrome are not fully understood, but some studies have shown a possible association with aberrant expression of Hox/SHH genes.[4]

Spina bifida

Spina bifida is a congenital anomaly in which the vertebral arch fails to fuse, leaving an area of the spinal cord that is open. The different forms of spina bifida are dependent on whether there is also herniation of meninges and/or spinal cord. Spina bifida occurs most often in the lower spinal region.[5]

Spina bifida occulta occurs when there is a vertebral arch deficit, but no involvement of meninges or spinal cord and the overlying skin stays intact. Spina bifida occulta is typically asymptomatic, and the defect is often incidentally found on a physical exam because it is associated with an overlying skin indentation or tuft of hair. Diagnostic confirmation can be via X-ray, showing no associated problems. No further treatment is necessary if this is the case.[1]

Spina bifida myelomeningocele occurs when there are a vertebral arch deficit and meninges, and spinal cord herniate through the associated defect. Patients with spina bifida myelomeningocele usually have a motor and sensory deficits at and below the level of the lesion. Other related problems that often occur include bowel and bladder incontinence as well as herniation of the hindbrain (also known as Chiari II malformation).[5] Spina bifida myelomeningocele is detectable before birth with increased AFP levels or ultrasound. Infants affected by this can survive with the appropriate treatment (often surgery to close affected area). However, even with treatment, there are usually lasting neurological deficits that vary depending on the vertebral level involved.[6]

Congenital scoliosis 

Abnormalities of vertebral formation and/or segmentation can result in scoliosis at birth. X-ray, CT scan, and MRI are all imaging used to diagnose. Scoliosis that presents at birth is different than scoliosis that develops in adolescence and often requires monitoring and/or surgery from birth.[7]

Klippel-Feil syndrome

Klippel-Feil syndrome is the result of the fusion of two or more cervical vertebrae due to the failure of segmentation in the embryological period.[8] Patients have characteristic physical features, including a short neck and low hairline.[9] This syndrome results in limited cervical mobility that can result in chronic headaches and pain.[10]

Congenital spondylolisthesis

Spondylolisthesis occurs when a vertebra or vertebrae slip forward about the vertebral column. An embryological defect that results in elongation of the pars interarticularis, most commonly at the lumbosacral junction, can predispose to spondylolisthesis that can result in neurological symptoms that require urgent surgery.[1]