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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.
Spondylocostal dysostosis is a rare condition, although its exact prevalence is unknown.
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.
Changes in these genes are associated with 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.
These resources address the diagnosis or management of spondylocostal dysostosis and may include treatment providers.
You might also find information on the diagnosis or management of spondylocostal dysostosis in Educational resources (http://ghr.nlm.nih.gov/condition/spondylocostal-dysostosis/show/Educational+resources) and Patient support (http://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.
You may find the following resources about spondylocostal dysostosis helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
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.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).
autosomal ; autosomal dominant ; autosomal recessive ; cell ; dwarfism ; embryonic ; gene ; hernia ; inguinal ; inheritance ; inheritance pattern ; inherited ; malformation ; prevalence ; recessive ; scoliosis ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
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.