Spondylocostal dysostosis

Reviewed February 2011

What is spondylocostal dysostosis?

Spondylocostal dysostosis is a group of conditions characterized by abnormal development of bones in the spine and ribs. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). Many people with this condition have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae. In addition to spine abnormalities, some of the rib bones may be fused together or missing. Affected individuals have short, rigid necks and short midsections because of the bone malformations. As a result, people with spondylocostal dysostosis have short bodies but normal length arms and legs, called short-trunk dwarfism.

The spine and rib abnormalities cause other signs and symptoms of spondylocostal dysostosis. Infants with this condition are born with small chests that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand in the narrow chest, the muscle that separates the abdomen from the chest cavity (the diaphragm) is forced down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia), particularly in males with spondylocostal dysostosis.

There are several types of spondylocostal dysostosis, designated types 1 through 4 and the autosomal dominant (AD) type. These types have similar features and are distinguished by their genetic cause and inheritance pattern. Spondylocostal dysostosis has often been grouped with a similar condition called spondylothoracic dysostosis, and both are called Jarcho-Levin syndrome; however, they are now considered distinct conditions.

How common is spondylocostal dysostosis?

Spondylocostal dysostosis is a rare condition, although its exact prevalence is unknown.

What genes are related to spondylocostal dysostosis?

Mutations in at least four genes are known to cause spondylocostal dysostosis: Mutations in the DLL3 gene cause spondylocostal dysostosis type 1; mutations in the MESP2 gene cause spondylocostal dysostosis type 2; mutations in the LFNG gene cause spondylocostal dysostosis type 3; and mutations in the HES7 gene cause spondylocostal dysostosis type 4. The genetic cause of AD spondylocostal dysostosis is unknown.

The DLL3, MESP2, LFNG, and HES7 genes play a role in the Notch signaling pathway, an important pathway in embryonic development. One of the functions of the Notch pathway is separating future vertebrae from one another during early development, a process called somite segmentation. When this pathway is disrupted, somite segmentation does not occur properly, resulting in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis.

Mutations in the four identified genes account for approximately 25 percent of diagnosed spondylocostal dysostosis. Researchers suggest that additional genes in the Notch signaling pathway might also be involved.

Related Gene(s)

Changes in these genes are associated with spondylocostal dysostosis.

DLL3
HES7
LFNG
MESP2

How do people inherit spondylocostal dysostosis?

Spondylocostal dysostosis can have different inheritance patterns. Types 1, 2, 3, and 4 are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. AD spondylocostal dysostosis is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of an altered gene in each cell is sufficient to cause the disorder, although in these cases no causative genes have been identified. The signs and symptoms of spondylocostal dysostosis are typically more severe with autosomal recessive inheritance.

Where can I find information about diagnosis or management of spondylocostal dysostosis?

These resources address the diagnosis or management of spondylocostal dysostosis and may include treatment providers.

Gene Review: Spondylocostal Dysostosis, Autosomal Recessive (http://www.ncbi.nlm.nih.gov/books/NBK8828/)
Genetic Testing Registry: Jarcho-Levin syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265343)
Genetic Testing Registry: Spondylocostal dysostosis 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837549)
Genetic Testing Registry: Spondylocostal dysostosis 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853296)
Genetic Testing Registry: Spondylocostal dysostosis 4, autosomal recessive (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150942)
KidsHealth: X-Ray Exam (Scoliosis) (http://kidshealth.org/parent/system/medical/xray_scoliosis.html)
MedlinePlus Encyclopedia: Scoliosis (http://www.nlm.nih.gov/medlineplus/ency/article/001241.htm)

You might also find information on the diagnosis or management of spondylocostal dysostosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/spondylocostal-dysostosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/spondylocostal-dysostosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about spondylocostal dysostosis?

You may find the following resources about spondylocostal dysostosis helpful. These materials are written for the general public.

MedlinePlus - Health information
- Encyclopedia: Scoliosis (http://www.nlm.nih.gov/medlineplus/ency/article/001241.htm)
- Health Topic: Scoliosis (http://www.nlm.nih.gov/medlineplus/scoliosis.html)
- Health Topic: Spine Injuries and Disorders (http://www.nlm.nih.gov/medlineplus/spineinjuriesanddisorders.html)
Additional NIH Resources - National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases: Scoliosis (http://www.niams.nih.gov/Health_Info/Scoliosis/default.asp)
Educational resources - Information pages
- Cleveland Clinic: Spinal X-ray (http://my.clevelandclinic.org/services/x-ray/hic_spine_x-ray.aspx)
- KidsHealth: Dwarfism (http://kidshealth.org/parent/growth/growth/dwarfism.html)
- National Organization for Rare Disorders: Jarcho-Levin Syndrome (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/704/viewAbstract)
- Orphanet: Autosomal recessive spondylocostal dysostosis (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2311)
Patient support - For patients and families
- Madisons Foundation: Jarcho-Levin Syndrome (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=558)
- Scoliosis Research Society (http://www.srs.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK8828/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Jarcho-Levin syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265343)
- Genetic Testing Registry: Spondylocostal dysostosis 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837549)
- Genetic Testing Registry: Spondylocostal dysostosis 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853296)
- Genetic Testing Registry: Spondylocostal dysostosis 4, autosomal recessive (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150942)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?term=%22spondylocostal%20dysostosis%22%20%5BDISEASE%5D%20OR%20NCT00001754%20%5BID-NUMBER%5D%20OR%20NCT00854828%20%5BID-NUMBER%5D%20OR%20NCT01087034%20%5BID-NUMBER%5D)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(spondylocostal%20dysostosis%5BTIAB%5D)%20OR%20((jarcho-levin%20syndrome%5BTIAB%5D)%20OR%20(scdo%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- SPONDYLOCOSTAL DYSOSTOSIS 1, AUTOSOMAL RECESSIVE (http://omim.org/entry/277300)
- SPONDYLOCOSTAL DYSOSTOSIS 2, AUTOSOMAL RECESSIVE (http://omim.org/entry/608681)
- SPONDYLOCOSTAL DYSOSTOSIS 3, AUTOSOMAL RECESSIVE (http://omim.org/entry/609813)
- SPONDYLOCOSTAL DYSOSTOSIS 4, AUTOSOMAL RECESSIVE (http://omim.org/entry/613686)
- SPONDYLOCOSTAL DYSOSTOSIS 5, AUTOSOMAL DOMINANT (http://omim.org/entry/122600)

What other names do people use for spondylocostal dysostosis?

Jarcho-Levin syndrome
SCDO

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about spondylocostal dysostosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding spondylocostal dysostosis?

autosomal ; autosomal dominant ; autosomal recessive ; cell ; dwarfism ; embryonic ; gene ; hernia ; inguinal ; inheritance ; inheritance pattern ; malformation ; prevalence ; recessive ; scoliosis ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Berdon WE, Lampl BS, Cornier AS, Ramirez N, Turnpenny PD, Vitale MG, Seimon LP, Cowles RA. Clinical and radiological distinction between spondylothoracic dysostosis (Lavy-Moseley syndrome) and spondylocostal dysostosis (Jarcho-Levin syndrome). Pediatr Radiol. 2011 Mar;41(3):384-8. doi: 10.1007/s00247-010-1928-8. Epub 2010 Dec 22. (http://www.ncbi.nlm.nih.gov/pubmed/21174082?dopt=Abstract)
Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat Genet. 2000 Apr;24(4):438-41. (http://www.ncbi.nlm.nih.gov/pubmed/10742114?dopt=Abstract)
Dunwoodie SL. Reprint of mutation of the fucose-specific beta1,3 N-acetylglucosaminyltransferase LFNG results in abnormal formation of the spine. Biochim Biophys Acta. 2009 Sep;1792(9):862-73. (http://www.ncbi.nlm.nih.gov/pubmed/19899223?dopt=Abstract)
Gucev ZS, Tasic V, Pop-Jordanova N, Sparrow DB, Dunwoodie SL, Ellard S, Young E, Turnpenny PD. Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: Negative mutation analysis of DLL3, MESP2, HES7, and LFNG. Am J Med Genet A. 2010 Jun;152A(6):1378-82. doi: 10.1002/ajmg.a.33471. (http://www.ncbi.nlm.nih.gov/pubmed/20503311?dopt=Abstract)
Sparrow DB, Chapman G, Turnpenny PD, Dunwoodie SL. Disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res C Embryo Today. 2007 Jun;81(2):93-110. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17600782?dopt=Abstract)
Sparrow DB, Guill�n-Navarro E, Fatkin D, Dunwoodie SL. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis. Hum Mol Genet. 2008 Dec 1;17(23):3761-6. doi: 10.1093/hmg/ddn272. Epub 2008 Sep 5. (http://www.ncbi.nlm.nih.gov/pubmed/18775957?dopt=Abstract)
Whittock NV, Sparrow DB, Wouters MA, Sillence D, Ellard S, Dunwoodie SL, Turnpenny PD. Mutated MESP2 causes spondylocostal dysostosis in humans. Am J Hum Genet. 2004 Jun;74(6):1249-54. Epub 2004 Apr 30. (http://www.ncbi.nlm.nih.gov/pubmed/15122512?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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