Classification and Etiologic Dissection of Vertebral Segmentation Anomalies

  • Peter D. Turnpenny


Congenital segmentation defects of the vertebrae (SDV) often give rise to early onset or congenital scoliosis (CS) and cover a multitude of diverse radiological and developmental phenotypes with various formation and segmentation anomalies. Single or multiple vertebrae may be affected and any spinal region involved. Anomalies of rib formation and alignment are commonly associated, and other organ systems may be involved as part of an underlying syndrome. In general, our understanding of the causation of this hugely diverse group of malformation conditions is poor but progress has been made through studying relatively rare families demonstrating mendelian inheritance. This group is dominated by the family of conditions known as the ‘spondylocostal dysostoses’ (SCD), where segmentation anomalies occur throughout the vertebral column. Four Notch signaling pathway genes are now linked to autosomal recessive (AR) SCD, types 1–4, and one to autosomal dominant (AD) SCD—type 5. SCD1 is caused by mutated delta-like 3 (DLL3) at chromosome 19q13.1; SCD2, and the severe spondylothoracic dysostosis (STD), is due to mutated mesoderm posterior 2 (MESP2) at 15q26; SCD3 is due to mutated LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase (LFNG) at 7p22; and SCD4 is due to mutated hairy and enhancer of split 7 (HES7) gene at 17p13.2. SCD5, following autosomal dominant (AD) inheritance, is due to mutated T-box 6 (TBX6) at 16p11.2. Klippel-Feil syndrome (KFS), characterised by fusion of the cervical vertebrae, also embraces much diversity. KFS1 and KFS3 are AD forms and due to mutated GDF6 (8p22.1) and GDF3 (12p13.3) respectively. KFS2 is AR and due to mutated MEOX1 (17q21). Vertebral segmentation anomalies are a variable feature of a wide variety of rare syndromes but for a high proportion of the diverse radiological and developmentally aberrant phenotypes seen in clinical practice the underlying cause is unknown. Further progress will depend on identifying causative genes in familial cases of CS/SDV, or cohorts of subjects with similar phenotypes, using next generation DNA sequencing. Several classifications for SDV, CS and KFS have been proposed and they are described.


Segmentation defects of the vertebrae (SDV) Spondylocostal dysostosis Spondylothoracic dysostosis Jarcho-Levin syndrome Klippel-Feil syndrome Notch signaling pathway Somitogenesis 


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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Clinical GeneticsRoyal Devon & Exeter HospitalExeterUK

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