OSMED, Heterozygous

OSMED, Heterozygous

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report OSMED, Heterozygous is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Oto-Spondylo-Megaepiphyseal Dysplasia, Autosomal Dominant
  • Oto-Spondylo-Megaepiphyseal Dysplasia, Heterozygous
  • Pierre-Robin Syndrome with Fetal Chondrodysplasia
  • Stickler Syndrome Type III
  • Weissenbacher-Zweymuller Syndrome
  • WZS

Disorder Subdivisions

  • None

General Discussion

Heterozygous OSMED (oto-spondyl-megaepiphyseal dysplasia) is a rare genetic disorder characterized by skeletal malformations resulting in shortening of the upper limbs and thighs and short stature (rhizomelic dwarfism). Additional symptoms include distinctive facial features and delays in psychomotor development. After the initial period of growth deficiency, affected individuals experience gradual improvement in bone growth that leads to normal physical development by early childhood. Mental and motor development is also normal by early childhood. In some cases, affected individuals develop hearing loss. Heterozygous OSMED occurs because of disruptions or changes (mutations) to the COL11A2 gene.



A group of collagen disorders (i.e., OSMED, Weissenbacher-Zweymuller syndrome and non-ocular Stickler syndrome or Stickler syndrome type III) are all caused by mutations to the COL11A2 gene (allelic disorders). Some researchers consider these three disorders separate entities; others believe that they are the same disorder or different expresses of one disorder. Recently, some researchers have suggested that the name OSMED be used as a general heading to consist of "heterozygous OSMED," which encompasses Weissenbacher-Zweymuller syndrome and Stickler syndrome type III and is inherited as an autosomal dominant trait and "homozygous OSMED," which encompasses autosomal recessive cases of oto-spondylo-megaepiphyseal dysplasia.

Symptoms

Heterozygous OSMED is characterized by skeletal malformations, distinct facial features and delayed psychomotor development. The specific symptoms affecting each child vary from case to case.



Affected children have abnormally short bones of the upper arms and thighs (rhizomelia) resulting in short stature during infancy and early childhood (rhizomelic dwarfism). The long bones of the upper arm (humeri) and thigh (femora) are short with broad heads (dumbbell-shaped). Affected individuals may also have clefts that resemble fractures in certain bones of the vertebrae (vertebral coronal clefts).



Affected infants may also exhibit a delay in the acquisition of skills requiring coordination of muscular and mental activity (psychomotor delays). As affected individuals age, they experience an increase in growth rate eventually reaching normal height by 5 or 6 years of age. Mental and motor development also becomes normal by this age.



Distinctive facial features associated with heterozygous OSMED include an abnormally small jaw (micrognathia), widely spaced eyes (hypertelorism), depressed nasal bridge, a small upturned nose, and underdevelopment of the bones of the middle portion of the face (midface hypoplasia) giving the face a flat appearance. Affected individuals may also have Pierre-Robin sequence, an assortment of abnormalities that may occur as a distinct syndrome or as part of another underlying disorder. Pierre-Robin sequence is characterized by an unusually small jaw (micrognathia), downward displacement or retraction of the tongue (glossoptosis), and incomplete closure of the roof of the mouth (cleft palate). Cleft palate may also occur as an isolated finding.



Some individuals develop hearing loss because of an impaired ability of the auditory nerves to transmit sensory input to the brain (sensorineural hearing loss). Such hearing loss may become progressively more pronounced.

Causes

Heterozygous OSMED is inherited as an autosomal dominant trait. Some cases occur randomly as the result of a spontaneous genetic change (i.e., new mutation). Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.



Investigators have determined that some cases of heterozygous OSMED occur due to changes or disruptions (mutations) of the collagen XI, apha-2 polypeptide (COL11A2) gene located on the short arm (p) of chromosome 6 (6p21.3). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body 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 6p21.3" refers to band 21.3 on the short arm of chromosome 6. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



The COL11A2 gene is involved in the formation (synthesis) of collagen, specifically type XI collagen. Collagen is the body's major structural protein forming an essential part of connective tissues and is the main component of ligaments, tendons and cartilage. Collagen is also found in bone. Type XI collagen is usually found in cartilage, the specialized tissue that serves as a buffer or cushion for bones at joints. The COL11A2 gene encodes for proteins that are essential to the development and function of type XI collagen. Mutations to this gene result in abnormalities in the production of collagen XI, which in turn affects the proper formation and development cartilage and bone.

Affected Populations

Heterozygous OSMED affects males and females in equal numbers. Both heterozygous and homozygous OSMED are extremely rare; approximately 30 cases have been reported in the medical literature. The exact incidence of this disorder is unknown. These disorders may be underdiagnosed making it difficult to determine their true frequency in the general population.



Heterozygous OSMED may be referred to as a type XI collagen disorder (collagenopathy). Type XI collagenopathies are disorders that involve abnormalities affecting type XI collagen and include homozygous OSMED and Stickler syndrome type II.

Standard Therapies

Diagnosis

A diagnosis of heterozygous OSMED is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms, and a variety of specialized tests including x-rays. X-ray studies reveal characteristic skeletal malformations associated with heterozygous OSMED.



Treatment

The treatment of heterozygous OSMED is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat abnormalities of the skeleton, joints, muscles, and related tissues (orthopedists), orthopedic surgeons, specialists who asses and treat hearing problems (audiologists), and other healthcare professionals may need to systematically and comprehensively plan an affect child's treatment.



Hearing aids may be used to treat hearing loss. Surgery may be necessary to correct certain skeletal malformations and abnormalities such as cleft palate. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

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

References

TEXTBOOKS

Gorlin RJ, Cohen MMJr, Hennekam RCM, eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:354-6.



Rimoin D, Connor JM, Pyeritz RP, Korf BR, eds. Emory and Rimoin's Principles and Practice of Medical Genetics. 4th ed. Churchill Livingstone. New York, NY; 2002:4082.



JOURNAL ARTICLES

Harel T, Rabinowitz R, Hendler N, et al. COL11A2 mutation associated with autosomal recessive Weissenbacher-Zweymuller syndrome: molecular and clinical overlap with otospondylomegaepiphyseal dysplasia (OSMED). Am J Med Genet. 2005;132:33-5.



Rabinowitz R, Gradstein L, Galil A, Levy J, Lifshitz T. The ocular manifestations of Weissenbacher-Zweymuller syndrome. Eye. 2004;18:1258-63.



Snead MP, Yates JRW. Clinical and molecular genetics of Stickler syndrome. J Med Genet. 1999;36:353-9.



Pihlajamaa T, Prockop DJ, Faber J, et al. Heterozygous glycine substation in the COL11A2 gene in the original patient with Weissenbacher-Zweymuller syndrome demonstrates its identity with heterozygous OSMED (nonocular Stickler syndrome). Am J Med Genet. 1998;80:115-20.



Spranger J. The type XI collagenopathies. Pediatr Radiol. 1998;28:745-50.



Ramer JC, Eggli K, Rogan PK, Ladda RL. Identical twins with Weissenbacher-Zweymuller syndrome and neural tube defect. Am J Med Genet. 1993;45:614-8.



Chemke J, Carmi R, Galil A, et al. Weissenbacher-Zweymuller syndrome: a distinct autosomal recessive skeletal dysplasia. Am J Med Genet. 1992;42:989-95.



Galil A, Carmi R, Goldstein E, et al, Weissenbacher-Zweymuller syndrome: long-term follow-up of growth and psychomotor development. Dev Med Child Neurol. 1991;33:1104-9.



FROM THE INTERNET

Robin NH, Moran RT, Warman W. Updated:08/05/2005. Stickler Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.genetests.org.



McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:277610; Last Update:06/16/2000. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=277610 Accessed on: May 26, 2006.



McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:184840; Last Update:06/16/2000. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=184840 Accessed on: May 26, 2006.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



Cleft Palate Foundation

1504 East Franklin Street

Suite 102

Chapel Hill, NC 27514-2820

USA

Tel: (919)933-9044

Fax: (919)933-9604

Tel: (800)242-5338

Email: info@cleftline.org

Internet: http://www.cleftline.org



Better Hearing Institute

1444 I Street NW

Suite 700

Washington, DC 20005

United States

Tel: (202)449-1100

Fax: (703)684-6048

Tel: (800)327-9355

Email: mail@betterhearing.org

Internet: http://www.betterhearing.org



Stickler Syndrome Support Group

PO Box 3351

Littlehampton, BN16 9GB

United Kingdom

Tel: 01903785771

Email: info@stickler.org.uk

Internet: http://www.stickler.org.uk



Stickler Involved People

15 Angelina

Augusta, KS 67010

Tel: (316)775-2993

Email: sip@sticklers.org

Internet: http://www.sticklers.org



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

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Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/



NIH/National Institute on Deafness and Other Communication Disorders

31 Center Drive, MSC 2320

Communication Avenue

Bethesda, MD 20892-3456

Tel: (301)402-0900

Fax: (301)907-8830

Tel: (800)241-1044

TDD: (800)241-1105

Email: nidcdinfo@nidcd.nih.gov

Internet: http://www.nidcd.nih.gov



Pierre Robin Network

3604 Biscayne

Quincy, IL 62305

USA

Tel: (217)224-0698

Fax: (217)224-2867

Email: info@pierrerobin.org

Internet: http://www.pierrerobin.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

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



American Academy of Audiology

11730 Plaza America Drive, Suite 300

Reston, VA 20190

Tel: (703)790-8466

Fax: (703)790-8631

Tel: (800)222-2336

Email: infoaud@audiology.org

Internet: http://www.audiology.org



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



Hearing Loss Association of America

7910 Woodmont Avenue

Suite 1200

Bethesda, MD 20814

Tel: (301)657-2248

Fax: (301)913-9413

Email: info@hearingloss.org

Internet: http://www.hearingloss.org



For a Complete Report

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