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Molecular Genetics Tests

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The spondylocostal dysostoses (SCDs) are a group of disorders characterised by multiple vertebral segmentation defects, truncal shortening and rib abnormalities.  Mutations in four genes causing a subset of autosomal recessively inherited forms of this disease have been identified.  Mutations have been identified in the DLL3 (SCD type 1), MESP2 (SCD type 2), LFNG (SCD type 3) and HES7 (SCD type 4) genes. 


SCD type 1 (DLL3 gene) is characterised by abnormal vertebral segmentation throughout the entire spine, with all vertebrae losing their normal form and regular three-dimensional shape. The most dramatic changes, affect the thoracic vertebrae and the ribs are malaligned with a variable number of points of fusion along their length. There is an overall symmetry of the thoracic cage and minor, nonprogressive, scoliotic curves that do not require corrective surgery. These features define SCD and all 4 forms of SCD have an overlapping and often indistinguishable phenotype (Turnpenny et al Dev Dyn. 236(6): 1456-1474).


SCD type 2 (MESP2 gene) is characterised by multiple segmentation defects of the vertebrae. Typically, all vertebrae show some degree of irregularity due to abnormal segmentation, though one family demonstrates more severe segmentation abnormalities of the cervical and thoracic spine as compared to the lumbar region (Whittock et al 2004 Am J Hum Genet 74:1249-1254)


STD (spondylothoracic dysostosis, Jarcho-Levin syndrome).  Mutations in the MESP2 gene have also been associated with spondylothoracic dysostosis.  This also follows autosomal recessive inheritance. The whole spine is shortened and an X-ray of the thoracic cage shows a ‘crab-like’ appearance of the ribs as they fan out from their costovertebral origins.  Unlike DLL3-associated SCD (SCD type 1), it is rare to see intercostal points of fusion in STD (Cornier et al 2008 Am J Hum Genet 82:1334-1341).


SCD type 3 (LFNG gene) is characterised by severe shortening of the spine and non-progressive scoliosis of the cervical and thoracic spine. Multiple vertebral ossification centres, with fitted angular shapes similar to SCD type 2 can be identified by x-ray and MRI scans, however, in contrast to SCD type 2, the vertebral anomalies are also present in the cervical and lumbar spine (Sparrow et al 2006 Am J Hum Genet 17:28-37).


SCD type 4 (HES7 gene) is characterised by shortening of the spine, with multiple and contiguous vertebral segmentation defects involving all spinal regions, but mainly the thoracic spine. Ribs are irregularly aligned, with variable points of fusion along their length. In the only published case report, the patient also presented with hydrocephaly, myelomeningocele, ectpoic stenotic anus and talipes (Sparrow et al 2008 Hum Mol Genet 17(23):3761-3766).


View Spondylocostal Dysostosis testing pathway


Before sending DNA for mutation screening, please e-mail a spinal X-ray (or send a slide/CD/copy X-ray) to the address below for clinical advice on which gene to screen first.


Dr. Peter Turnpenny
Clinical Genetics
Royal Devon & Exeter Hospital (Heavitree)
Gladstone Road
Exeter EX1 2ED



Known Mutation


DLL3 exons 2-9 analysis by sequencing
MESP2 exons 1-2 analysis by sequencing
LFNG exons 1-8 analysis by sequencing
HES7 exons 1-4 analysis by sequencing

Prenatal testing

(by prior arrangement with the laboratory)




Mutation detection rate for samples received for DLL3, MESP2, LFNG and HES7 testing up to 31st March 2012