X-linked spondyloepiphyseal dysplasia tarda

Reviewed June 2008

What is X-linked spondyloepiphyseal dysplasia tarda?

X-linked spondyloepiphyseal dysplasia tarda is a condition that impairs bone growth and occurs almost exclusively in males. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends (epiphyses) of long bones in the arms and legs. "Tarda" indicates that signs and symptoms of this condition are not present at birth, but appear later in childhood, typically between ages 6 and 10.

Males with X-linked spondyloepiphyseal dysplasia tarda have skeletal abnormalities and short stature. Affected boys grow steadily until late childhood, when their growth slows. Male adult height ranges from 4 feet 10 inches to 5 feet 6 inches. Individuals with X-linked spondyloepiphyseal dysplasia tarda have a short trunk and neck, and their arms appear disproportionately long. Impaired growth of the spinal bones (vertebrae) causes the short stature seen in this disorder. The spinal abnormalities include flattened vertebrae (platyspondyly) with hump-shaped bulges, progressive thinning of the discs between vertebrae, and an abnormal curvature of the spine (scoliosis or kyphosis). Other skeletal features of X-linked spondyloepiphyseal dysplasia tarda include an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); a broad, barrel-shaped chest; and decreased mobility of the elbow and hip joints. Arthritis often develops in early adulthood, typically affecting the hip joints and spine.

How common is X-linked spondyloepiphyseal dysplasia tarda?

The prevalence of X-linked spondyloepiphyseal dysplasia tarda is estimated to be 1 in 150,000 to 200,000 people worldwide.

What genes are related to X-linked spondyloepiphyseal dysplasia tarda?

Mutations in the TRAPPC2 gene (often called the SEDL gene) cause X-linked spondyloepiphyseal dysplasia tarda. The TRAPPC2 gene provides instructions for producing the protein sedlin. The function of sedlin is unclear. Researchers believe that sedlin is part of a large molecule called the trafficking protein particle (TRAPP) complex, which plays a role in the transport of proteins between various cell compartments (organelles). Because sedlin is active (expressed) in cells throughout the body; it is unclear why mutations in the TRAPPC2 gene affect only bone growth.

Related Gene(s)

Changes in this gene are associated with X-linked spondyloepiphyseal dysplasia tarda.

TRAPPC2

How do people inherit X-linked spondyloepiphyseal dysplasia tarda?

X-linked spondyloepiphyseal dysplasia tarda is inherited in an X-linked recessive pattern. The TRAPPC2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a TRAPPC2 mutation may develop arthritis in early adulthood.

Where can I find information about diagnosis or management of X-linked spondyloepiphyseal dysplasia tarda?

These resources address the diagnosis or management of X-linked spondyloepiphyseal dysplasia tarda and may include treatment providers.

Gene Review: Spondyloepiphyseal Dysplasia Tarda, X-Linked (http://www.ncbi.nlm.nih.gov/books/NBK1145/)
Genetic Testing Registry: Spondyloepiphyseal dysplasia tarda (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0220776)

You might also find information on the diagnosis or management of X-linked spondyloepiphyseal dysplasia tarda in Educational resources (http://www.ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/x-linked-spondyloepiphyseal-dysplasia-tarda/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 X-linked spondyloepiphyseal dysplasia tarda?

You may find the following resources about X-linked spondyloepiphyseal dysplasia tarda helpful. These materials are written for the general public.

MedlinePlus - Health information
- Health Topic: Bone Diseases (http://www.nlm.nih.gov/medlineplus/bonediseases.html)
- Health Topic: Osteoarthritis (http://www.nlm.nih.gov/medlineplus/osteoarthritis.html)
- Health Topic: Scoliosis (http://www.nlm.nih.gov/medlineplus/scoliosis.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/4985/resources/resources/1)
Additional NIH Resources - National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases: Arthritis (http://www.niams.nih.gov/Health_Info/Osteoarthritis/default.asp)
Educational resources - Information pages
- Cedars-Sinai Medical Center: International Skeletal Dysplasia Registry (http://isdr.csmc.edu/)
- Cincinnati Children's Hospital: Coxa Vera (http://www.cincinnatichildrens.org/health/c/coxavara/)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=253)
- Swedish Information Center for Rare Diseases (http://www.socialstyrelsen.se/rarediseases/late-onsetspondyloepiphysealdy)
Patient support - For patients and families
- Family Village (http://www.familyvillage.wisc.edu/lib_grow.htm)
- National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/294/viewAbstract)
- Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/dwarfism.html)
- The Human Growth Foundation (http://www.hgfound.org/)
- The MAGIC Foundation (http://www.magicfoundation.org/www)

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/NBK1145/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Spondyloepiphyseal dysplasia tarda (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0220776)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22X-linked%20spondyloepiphyseal%20dysplasia%20tarda%22%20OR%20%22Spondyloepiphyseal%20Dysplasia%22%20OR%20%22Dysplasias%2C%20Spondyloepiphyseal%22%20OR%20%22Dysplasia%2C%20Spondyloepiphyseal%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Osteochondrodysplasias%5BMAJR%5D)%20AND%20((x-linked%20spondyloepiphyseal%20dysplasia%20tarda%5BTIAB%5D)%20OR%20(spondyloepiphyseal%20dysplasia%20tarda%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/313400)

What other names do people use for X-linked spondyloepiphyseal dysplasia tarda?

Dysplasia, Spondyloepiphyseal
Late-onset spondyloepiphyseal dysplasia
SED tarda
Spondyloepiphyseal Dysplasia
X-linked SED
X-linked SEDT

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 X-linked spondyloepiphyseal dysplasia tarda?

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

What glossary definitions help with understanding X-linked spondyloepiphyseal dysplasia tarda?

arthritis ; carrier ; cell ; chromosome ; coxa vara ; dysplasia ; expressed ; gene ; inheritance ; joint ; molecule ; mutation ; prevalence ; protein ; recessive ; scoliosis ; sex chromosomes ; short stature ; stature ; X-linked recessive

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

References

Christie PT, Curley A, Nesbit MA, Chapman C, Genet S, Harper PS, Keeling SL, Wilkie AO, Winter RM, Thakker RV. Mutational analysis in X-linked spondyloepiphyseal dysplasia tarda. J Clin Endocrinol Metab. 2001 Jul;86(7):3233-6. (http://www.ncbi.nlm.nih.gov/pubmed/11443194?dopt=Abstract)
Fiedler J, Le Merrer M, Mortier G, Heuertz S, Faivre L, Brenner RE. X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families. Hum Mutat. 2004 Jul;24(1):103. (http://www.ncbi.nlm.nih.gov/pubmed/15221797?dopt=Abstract)
Gedeon AK, Tiller GE, Le Merrer M, Heuertz S, Tranebjaerg L, Chitayat D, Robertson S, Glass IA, Savarirayan R, Cole WG, Rimoin DL, Kousseff BG, Ohashi H, Zabel B, Munnich A, Gecz J, Mulley JC. The molecular basis of X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet. 2001 Jun;68(6):1386-97. Epub 2001 May 8. (http://www.ncbi.nlm.nih.gov/pubmed/11349230?dopt=Abstract)
Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). Eur J Hum Genet. 2003 Sep;11(9):639-42. (http://www.ncbi.nlm.nih.gov/pubmed/12939648?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.