Rare Nephrology News

Disease Profile

Spondylothoracic dysostosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q76.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Spondylothoracic dysplasia; Jarcho-Levin syndrome

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary

Spondylothoracic dysostosis (STD) is a rare condition that affects the bones of the spine and the ribs.[1] The term “Jarcho-Levin syndrome” in many cases is used as a synonym for STD, and sometimes as a synonym for another condition known as spondylocostal dysostosis, which has several common features with STD. Also, the term “Jarcho-Levin syndrome” is often used for all radiologic features that include defects of the vertebrae and abnormal rib alignment.[2] Signs and symptoms of STD are generally present at birth and may include short-trunk dwarfism (a short body with normal length arms and legs); a small chest cavity; misshapen and abnormally-fused vertebrae (bones of the spine); and fused ribs at the part nearest the spine. Affected people may also have life-threatening breathing problems and recurrent lung infections, which can significantly reduce lifespan. It can occur in any population; however, it occurs most frequently in people of Puerto Rican ancestry.[3] It is caused by changes (mutations) in the MESP2 gene and is inherited in an autosomal recessive manner.[1][3][4] Treatment is based on the signs and symptoms present and may include surgery for bone malformations and respiratory support.[4]

Symptoms

Signs and symptoms of spondylothoracic dysostosis include spine and vertebral abnormalities, which result in a shortened spine, neck, and trunk, as well as rib anomalies including fused ribs. This combination of features result in a "crab-like" appearance to the rib cage. Although the neck and midsection of individuals with spondylothoracic dysostosis are shortened, the arms and legs grow normally. As such, individuals with spondylothoracic dysostosis have short stature and are said to have short-trunk dwarfism.[3][1]

The spine and rib abnormalities may cause other complications. Infants with this condition are born with a small chest that cannot expand appropriately. This often leads to life-threatening breathing problems. As the lungs expand, the narrow chest forces the muscle that separates the abdomen from the chest cavity (the diaphragm) 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) or belly-button (umbilical hernia).[1]

Most individuals with spondylothoracic dysostosis have normal intelligence and neurological problems are infrequent.[5]

Symptom severity may vary from patient to patient with spondylothoracic dysostosis; however, symptoms tend to be the worse for individuals who carry two E230X mutations in the MESP2 gene.[3]

Cause

Spondylothoracic dysostosis is caused by mutations in the MESP2 gene. The MESP2 gene codes for the MESP2 protein, which controls the activities of genes in a pathway called the Notch pathway. The Notch pathway plays an important role in the development of structures in the prenatal period, specifically the development and proper separation of the vertebrae (bones that form the spinal column). This process is called somite segmentation.

Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, somite segmentation does not occur properly, which results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.[3][1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no cure for spondylothoracic dysostosis. Treatment usually consists of intensive medical care, including early and aggressive treatment of respiratory infections, physical therapy, bone surgery, and orthopedic treatment.[6][7] Surgery may then be needed for chest wall or spine deformities, such as severe scoliosis. An external bracing, for example, by use of an expandable prosthetic titanium rib may be used for some cases.[2]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Spondylothoracic dysostosis. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Spondylothoracic dysostosis. Click on the link to view a sample search on this topic.

            References

            1. Spondylothoracic dysostosis. Genetics Home Reference. February 2011; https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis.
            2. Turnpenny PD, Young E. Spondylocostal Dysostosis, Autosomal Recessive. GeneReviews. January 2013; https://www.ncbi.nlm.nih.gov/books/NBK8828/.
            3. Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD, Pourquié O. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun; 82(6):1334-41. https://www.ncbi.nlm.nih.gov/pubmed/18485326.
            4. Mark C Lee, MD. Congenital Spinal Deformity. Medscape Reference. February 2015; https://emedicine.medscape.com/article/1260442-overview#a1.
            5. Kulkarni ML, Navaz SR, Vani HN, Manjunath KS, Matani D. Jarchho-Levin syndrome.. Indian J Pediatr. 2006 Mar; 73(3):245-7. https://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=DetailsSearch&Term=16567923%5Buid%5D.
            6. Spondylocostal dysostosis, autosomal recessive. Orphanet. February 2005; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2311.
            7. María E. Vázquez-Lópeza, María I. López-Condea, Carlos Somoza-Rubioa, Roberto Pérez-Pacína, Ramón Morales-Redondoa, Miguel A. González-Gay. Anomalies of vertebrae and ribs: Jarcho Levin syndrome. Description of a case and literature review. Joint Bone Spine. May 2005; 72(3):275-277. https://www.ncbi.nlm.nih.gov/pubmed/15851003.

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