Spondyloepiphyseal Dysplasia Tarda

Spondyloepiphyseal Dysplasia Tarda

National Organization for Rare Disorders, Inc.

Important

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Synonyms

  • SED tarda
  • X-linked spondyloepiphyseal dysplasia

Disorder Subdivisions

  • None

General Discussion

Spondyloepiphyseal dysplasia tarda (SEDT; SEDL) is a rare, hereditary skeletal disorder that only affects males. Physical characteristics include moderate short stature (dwarfism), moderate-to-severe spinal deformities, barrel-shaped chest, disproportionately short trunk, and premature osteoarthritis.

Symptoms

Symptoms of SEDT are usually not apparent until six to eight years of age, hence the distinction "tarda" or "late". This is the most obvious distinction from the congenital form (SED congenita, or SEDC), which is usually obvious at birth. Unlike SEDC, cleft palate and retinal detachment are not associated with SEDT.



At about 6 to 8 or 10 years, spinal growth appears to decline and then stops. Limb growth continues, resulting in a disproportionately short trunk. Arm span may exceed height by 4 to 8 inches. The shoulders may assume a hunched appearance, the neck appears short and the chest broadens (barrel chest). During adolescence, various skeletal abnormalities may cause pain in the back, hips, shoulders, knees and ankles. Some individuals with SEDT may have a flat appearance to the face, but the shape of the head is usually normal. As adults, people with SEDT have mild dwarfism, with a short trunk, large chest cage and relatively normal limb length. Hands, head and feet appear to be normal size, and final adult height usually ranges from 4'10" to 5'6".

Causes

SEDT is inherited as an X-linked recessive genetic trait. The locus has been mapped to the short arm of the X chromosome at Xp22.2-p22.1. The gene, known as SEDL or TRAPPC2, is widely expressed in tissues throughout the body, but when mutated or deleted appears to only affect cartilage. Its primary function is unknown, but it may play a role in intracellular protein trafficking [Gedeon et al 1999] or gene regulation [Jeyabalan et al, 2010].



Chromosomes, which are present in the nucleus of all cells, carry the genetic information for each individual. Human cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome Xp22.2-p22.1" refers to a region between bands 22.1 and 22.2 on the short arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes, but one of the X chromosomes is normally "turned off" early in fetal development, and most of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder, but rarely display any of its manifestations.



Males have one X chromosome and, if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because fathers pass their Y chromosome to their male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

Affected Populations

SEDT does not exhibit any ethnic predisposition. Affected individuals have been described in European, American, Asian, and Australian populations (but not in African-Americans to date). One estimate suggests that the incidence is 2 persons per million.

Standard Therapies

Diagnosis

The diagnosis of SEDT is usually made on the basis of characteristic radiological (X-ray) findings. These appear in late childhood but usually before puberty.[[no paragraph]] Some of these signs are: flattened vertebral bodies (platyspondyly), typical distortions of the upper and lower vertebral surfaces ("humping"), short necks of the thigh bones (femurs), an angular deformity of the neck of the femur (coxa vara), and signs of early arthritis, especially in the hip joints.



Molecular testing for mutations in the SEDL (TRAPPC2) gene is commercially available.



Treatment

Treatment is supportive and symptomatic. Hip replacement may be necessary by the fourth to fifth decade of life.

Investigational Therapies

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:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Contact for additional information about spondyloepiphyseal dysplasia tarda:



George E Tiller, MD, PhD

Regional Chief, Department of Genetics

Southern California Permanente Medical Group

Tel (LAMC) 323-783-1916 (voicemail)

Tel (LAMC) 323-783-5612 (secretary)

FAX (LAMC) 323-783-5208

References

TEXTBOOKS

Unger S, Lachman RS, Rimoin DL: Chondrodysplasias. In Rimoin DL, Connor JM, Pyeritz RE, Korf, BR (eds): Emery & Rimoin's Principles and Practice of Medical Genetics, 5th ed. New York, Churchill Livingstone, 2007, pp 3709-3753.



Jones KL. Ed. Smith's Recognizable Patterns of Human Malformation. 6th ed. WB Saunders, Philadelphia, 2006:426-7.



Hicks J. Spondyloepiphyseal Dysplasia Tarda. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:729-30.



JOURNAL ARTICLES

Jeyabalan J, Nesbit MA, Galvanovskis J, Callaghan R, Rorsman P, Thakker RV. SEDLIN forms homodimers: characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1. PLoS One 2010; 5(5):e10646



Gedeon AK, Tiller GE, Le Merrer M, et al. The molecular basis of X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet. 2001;68:1386-97.



Tiller GE, Hannig VL, Dozier D, et al. A recurrent RNA-splicing mutation in the SEDL gene causes X-linked spondyloepiphyseal dysplasia tarda. Am J Hum Genet.2001;68:1398-407.



Whyte MP, Gottesman GS, Eddy MC, McAlister WH. X-linked recessive spondyloepiphyseal dysplasia tarda: clinical and radiographic evolution in a 6-generation kindred and review of the literature. Medicine.1999;78:9-25.



Gedeon AK, Colley A, Jamieson R, et al. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nat Genet. 1999;22:400-04.



FROM THE INTERNET

Tiller GE, Hannig VL. (Updated February 15, 2011). X-Linked Spondyloepiphyseal Dysplasia Tarda. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed February 18, 2011.



X-linked spondyloepiphyseal dysplasia tarda. Genetics Home Reference (GHR). June 2008 Available at: http://ghr.nlm.nih.gov/condition=xlinkedspondyloepiphysealdysplasiatarda. Accessed February 9, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spondyloepiphyseal Dysplasia Tarda, X-Linked. Entry No: 313400. Last Edited January 13, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 18, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Tracking Protein Particle Complex, Subunit 2. Entry No: 300202. Last Edited April 20, 2007. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 18, 2011.

Resources

Human Growth Foundation

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Coalition for Heritable Disorders of Connective Tissue (CHDCT)

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Genetic and Rare Diseases (GARD) Information Center

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Fax: (301)251-4911

Tel: (888)205-2311

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Internet: http://rarediseases.info.nih.gov/GARD/



European Skeletal Dysplasia Network

Institute of Genetic Medicine

Newcastle University

International Centre for Life

Central Parkway

Newcastle upon Tyne, NE1 3BZ

United Kingdom

Tel: 441612755642

Fax: 441612755082

Email: info@esdn.org

Internet: http://www.esdn.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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