Última actualización:
October 16, 2017
Años publicados: 2017
NORD gratefully acknowledges Robert M. Campbell Jr., MD, Division of Orthopaedics, Director, The Center for Thoracic Insufficiency Syndrome, The Children’s Hospital of Philadelphia, for assistance in the preparation of this report.
Summary
Spondylothoracic dysplasia (STD) is a rare disorder in which there are malformations affecting the spine and ribs. The portion of the spine supporting the chest is extremely shortened. These malformations are present at birth (congenital). The bones of the spine called the vertebrae do not develop properly, and commonly fuse together with the adjacent ribs fusing to the spine. On an x-ray this gives the thorax a crab-like shape. The thorax is the portion of the body extending from the neck to the abdomen and includes the cavity surrounded by the ribs, breastbone and certain vertebrae. The shortened chest can restrict the size of the lungs, causing thoracic insufficiency syndrome. Spondylothoracic dysplasia can cause severe breathing (respiratory) problems and infants are at risk of life-threatening respiratory failure. Affected individuals are shorter than would otherwise be expected based on their age and gender (short stature) and may have an abnormal curvature to the spine. Many people with spondylothoracic dysplasia have a change (mutation) in the MESP2 gene. This gene change is inherited in an autosomal recessive manner.
Introduction
There is significant confusion in the medical literature regarding names for spondylothoracic dysplasia. For years, this disorder and a similar disorder, spondylocostal dysplasia (were considered the same disorder and referred to as Jarcho-Levin syndrome. Researchers now know that these disorders are separate entities with different causes and associated malformations. The term Jarcho-Levin syndrome is still used for both disorders, and sometimes it is used as an “umbrella” term to describe a broad range of conditions associated with spinal and rib defects. This has led to confusion for individuals and families who receive a diagnosis of Jarcho-Levin syndrome. Some researchers have advocated that Jarcho-Levin syndrome be reserved for people with spondylocostal dysplasia and the eponym Lavy-Moseley syndrome be used for spondylothoracic dysplasia. Other researchers believe the widespread, inconsistent use of Jarcho-Levin syndrome has rendered the term obsolete and that its use should be discontinued. Jarcho and Levin were two doctors who first described what is now known as spondylothoracic dysplasia in the medical literature in 1938.
The spine and ribs do not develop properly in spondylothoracic dysplasia. The bones of the spine are malformed and may be fused together. This fusion occurs where the head of the rib bones connects to the bones of the thoracic spine. The thoracic spine is the portion of the spinal column that makes up the upper and lower back. Because of the abnormal fusion of these bones, the affected area has a crab-like shape on x-rays. The spine can be markedly shorter than normal. Some individuals with STD may have an abnormal curve to the spine. The spine may be s-shaped (scoliosis), abnormally curved inward (lordosis), or abnormally curved outward (kyphosis), causing the back to appear rounded. Most patients with STD have a short straight spine.
The trunk, which is the part of the body that extends from the neck to the abdomen, may be disproportionately smaller in comparison to height. In addition, affected individuals may be shorter than would otherwise be expected for their age and gender (short stature). Affected individuals may have a short neck with limited mobility.
Because of the malformation of the spine and ribs, the lungs of affected infants and children may not be able to grow and develop properly. Affected infants and children cannot expand their chests sufficiently, causing reduced lung capacity, which means the lungs can hold less air than they normally would. Consequently, people with this condition can have difficulties breathing and experience repeated respiratory infections. Breathing problems can be severe and can become life-threatening and be fatal. Reduced lung capacity can also increase the risk of heart failure.
There is an increased risk of developing inguinal hernia, a condition characterized by protrusion of parts of the large intestine through an opening in the abdominal wall near the groin as well as protrusion of parts of the large intestine through an opening near the belly button (umbilical hernia).
Spondylothoracic dysplasia is caused by a change (mutation) in the MESP2 gene. Most affected people have a mutation in this gene, but sometimes people with this disorder do not have a mutation in the MESP2 gene, suggesting that as-yet-unidentified gene(s) also cause the disorder. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body.
Spondylothoracic dysplasia is inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
The MESP2 gene that causes spondylothoracic dysplasia produces a protein that is involved in the NOTCH signaling pathway. This pathway is a series of chemical reactions that are vital to the health and function of the body, particularly with the development of the spine and ribs. The protein produced by the altered MESP2 gene is inefficient or defective, or the gene does not produce enough of the protein. Without the protein in question, the normal chemical reactions that occur in the NOTCH signaling pathway are impaired, leading to the signs and symptoms of spondylothoracic dysplasia.
Spondylothoracic dysplasia occurs with greater frequency in Puerto Rico and in individuals of Puerto Rican heritage, accounting for about half of all affected individuals reported in the medical literature.
A diagnosis of spondylothoracic dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.
Clinical Testing and Workup
X-rays (radiographs) of the spine can show characteristic changes to the spine and ribs that characterized spondylothoracic dysplasia.
A diagnosis of spondylothoracic dysplasia can be confirmed through molecular genetic testing in some individuals. Molecular genetic testing can detect alterations in the MESP2 gene known to cause the disorder, but is available only as a diagnostic service at specialized laboratories. Also, some people may not have a mutation in this gene, and their diagnosis cannot be confirmed through molecular genetic testing.
Prenatal diagnosis of spondylothoracic dysplasia is possible by fetal ultrasound. An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can reveal some of the defects associated with spondylothoracic dysplasia.
Treatment
The treatment of spondylothoracic dysplasia is directed toward the specific symptoms that are apparent in an individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat skeletal disorders (orthopedists), orthopedic surgeons, specialists who diagnose and assess heart disorders (cardiologists), specialists who diagnose and treat lung disorders (pulmonologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.
Infants who experience breathing difficulties can require some form of respiratory support. This can include the use of a machine or device to help an infant breath. Some infants may require intensive care, which involves constant monitoring in a hospital. Surgery is used to repair an inguinal hernia. Scoliosis is rare in STD, but VEPTR thoracic surgery may be beneficial in increasing chest size to maximize lung growth potential. Antibiotics may be necessary to treat recurrent respiratory infections.
The vertical expandable prosthetic titanium rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. For treatment of spondylothoracic dysplasia, ribs are separated on each side of the chest and VEPTRs are placed on each side of the chest. It is manufactured by DePuy Synthes Spine Co. in Raynham Mass.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
For more information about spondylothoracic dysplasia please contact:
Robert M. Campbell Jr., MD
Division of Orthopaedics
Director, The Center for Thoracic Insufficiency Syndrome
The Children’s Hospital of Philadelphia
34th and Civic Center Blvd.
2nd Floor, Wood Bldg.
Philadelphia, PA 19104
[email protected]
https://www.chop.edu/centers-programs/center-thoracic-insufficiency-syndrome
TEXTBOOKS
Campbell RM. VEPTR Expansion Thoracoplasty. In: The Growing Spine. Management of Spinal Disorders in Children, Akbarnia BA, Yazici M, Thompson GH, editors. 2016 Springer-Verlag, Berlin. Pp. 669-690.
Jones KL, Jones MC, del Campo Casanelles. Eds. Jarcho-Levin syndrome. In: Smith’s Recognizable Patterns of Human Malformation. 7th ed. Elsevier Saunders, Philadelphia, PA; 2013:782-783.
Campbell RM. Jarcho-Levin syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:207-208.
JOURNAL ARTICLES
Karlin JG, Roth MK, Patil V, et al. Management of thoracic insufficiency syndrome in patients with Jarcho-Levin syndrome using VEPTRs (vertical expandable prosthetic titanium ribs). J Bone Joint Surg Am. 2014;96:e181. https://www.ncbi.nlm.nih.gov/pubmed/25378514
Berndon WE, Lampl BS, Cornier AS, et al. Clinical and radiological distinction between spondylothoracic dysostosis (Lavy-Moseley syndrome) and spondylocostal dysostosis (Jarcho-Levin syndrome). Pediatr Radiol. 2011;41-384-388. https://www.ncbi.nlm.nih.gov/pubmed/21174082
Offiah A, Alman B, Cornier AS, et al. Pilot assessment of a radiologic classification system for segmentation defects of the vertebrae. Am J Med Genet A. 2010;152A:1357-1371. https://www.ncbi.nlm.nih.gov/pubmed/20503308
Campbell RM Jr. Spine deformities in rare congenital syndromes: clinical issues. Spine (Phil Pa 1976). 2009;134:1815-1827. https://www.ncbi.nlm.nih.gov/pubmed/19644333
Giampietro PF, Dunwoodie SL, Kusumi K, et al. Progress in the understanding of the genetic etiology of vertebral segmentation disorders in humans. Ann NY Acad Sci. 2009;1151:38-67. https://www.ncbi.nlm.nih.gov/pubmed/19154516
Cornier AS, Staehling-Hamptom K, Delventhal KM, et al. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008;82:1334-1341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427230/
Ramírez N, Cornier AS, Campbell RM Jr, et al. Natural history of thoracic insufficiency syndrome: a spondylothoracic dysplasia perspective. J Bone Joint Surg Am. 2007 Dec;89(12):2663-75. https://www.ncbi.nlm.nih.gov/pubmed/18056499
Kulkarni ML, Navaz SR, Vani NH, Manjunath KS, Matani D. Jarcho-Levin syndrome. Indian J Pediatr. 2006;73:245-247. https://www.ncbi.nlm.nih.gov/pubmed/16567923
Karnes PS, Day D, Berry SA, Pierpont ME. Jarcho-Levin syndrome: four new cases and classification of subtypes. Am J Med Genet. 1991;40:264-270. https://www.ncbi.nlm.nih.gov/pubmed/1951427
INTERNET
Genetics Home Reference. Spondylothoracic Dysostosis.Reviewed June 2016. Available at: https://ghr.nlm.nih.gov/condition/spondylothoracic-dysostosis# Accessed: September 28, 2017.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:277300; Last Update: 10/03/2016. Available at: https://omim.org/entry/277300 Accessed: September 28, 2017.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report