OSMED, Homozygous

OSMED, Homozygous

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report OSMED, Homozygous 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 recessive
  • oto-spondylo-megaepiphyseal dysplasia, homozygous
  • Nance-Sweeney syndrome

Disorder Subdivisions

  • None

General Discussion

Homozygous OSMED (oto-spondylo-megaepiphyseal dysplasia) is an extremely rare genetic disorder characterized by malformation (dysplasia) of certain bones, hearing loss and distinct facial features. Skeletal malformations affect the bones of the arms, legs and spines eventually resulting in disproportionate short stature. Hearing loss is often severe. Intelligence is normal. Homozygous OSMED occurs because of disruptions or changes (mutations) to the COL11A2 gene and is inherited as an autosomal recessive trait.



Two additional disorders, Weissenbacher-Zweymuller syndrome and Stickler syndrome III, more commonly known as non-ocular Stickler syndrome, are also caused by mutations to this gene (allelic disorders). Some clinical researchers believe that each of these three disorders is a separate and distinct entity. Others believe that the three represent a range of severity of one syndrome. Regardless, these disorders involve alterations (mutations) of the collagen gene, COL11A2. 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

Symptoms associated with homozygous OSMED vary from case to case. Affected individuals have progressive, severe hearing loss, skeletal malformations and distinctive facial features.



Hearing loss in individuals with homozygous OSMED may be progressive and severe and occurs because of an impaired ability of the auditory nerves to transmit sensory input to the brain (sensorineural hearing loss). During infancy, affected individuals may also experience feeding difficulties, recurrent pulmonary infections, and inflammation of the main air passages (bronchioles) to the lung (bronchitis), and pneumonia.



Skeletal abnormalities associated with homozygous OSMED include malformation (dysplasia) of the long bones of the arms (humeri) and legs (femora). The "growing portion" or head of the long bones (epiphyses) is abnormally large and broad and the end portion of the shaft of the long bones is abnormally widened (metaphyseal flaring) resulting in a dumbbell shape. Affected individuals may also have joint contractures, abnormally large bones of the ankle (tarsal bones), and short hands with stubby fingers. In some cases, the upper portion (capital) of the thighbone where it meets the hip (capital femoral epiphyses) is abnormally small or absent. As affected individuals age, they may develop progressive front-to-back curvature of the spine (lordosis) and large, painful joints with reduced mobility. Skeletal abnormalities associated with homozygous OSMED eventually result in short stature with disproportionately short limbs.



Affected individuals may also develop osteoarthritis, a condition characterized by the breakdown of cartilage and pain, degeneration, and stiffness of affected joints. Individuals with homozygous OSMED also have flattening of the central regions of bones in the spinal column (platyspondyly) and progressive fusion of the eight small bones of the wrists (carpal bones).



Distinctive facial features associated with homozygous OSMED include an underdeveloped jaw bone (mandibular hypoplasia), a rounded (bulbous) upturned nose with nostrils that are flared forward (anteverted nares), and underdevelopment of the bones of the middle of the face (midface hypoplasia) resulting in a flat facial 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

Causes

Homozygous OSMED is inherited as an autosomal recessive trait. 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.



Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives 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 defective gene and, therefore, 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 and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



Some individuals with homozygous OSMED have parent who were closely related. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.



Homozygous OSMED appears to occur as a result of 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 of cartilage and bone.

Affected Populations

Homozygous OSMED affects males and females in equal numbers. The disorder was first described in the medical literature in 1970.



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

Standard Therapies

Diagnosis

A diagnosis of homozygous 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 homozygous OSMED. Genetic testing is also available to scan for mutations of genes coding for collagen XI.



Treatment

The treatment of homozygous 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

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.



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



Magalini SI, et al, eds. Dictionary of Medical Syndromes. 4th ed.New York, NY: Lippincott-Raven Publishers; 1997:571



JOURNAL ARTICLES

Temtamy SA, Mannikko M, Abdel-Salam GM, et al. Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical and radiological findings in sibs homozygous for premature stop codon mutation in the COL11A2 gene. Am J Med Genet. 2006;[Epub ahead of print].



Miyamoto Y, Nakashima E, Hiraoka H, Ohashi I, Ikegawa S. A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia. Hum Genet. 2005;118:175-8.



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.



Bigozzi M, Cerboni F, Pellegrini A. 2 cases of oto-spondylo-megaepiphyseal dysplasia. Acta Otorhinolaryngol Ital. 2001;21:179-86.



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.



Van Steensel MA, Buma P, de Waal Malefijt MC, van den Hoogen FH, Brunner HG. Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical description of three patients homozygous for a missense mutation in the COL11A2 gene. Am J Med Genet. 1997;70:315-23.



Katbamna B, Westbrook MK. Hearing loss in oto-spondylo-megaepiphysealdysplasia (OSMED): case studies. J Am Acad Audiol. 1996;7:365-9.



Rosser EM, Hall CM, Harper J, Lacour M, Baraitser M. Nance-Sweeney chondrodysplasia - a further case? Clin Dysmorphol. 1996;5:207-12.



Vikkula M, Mariman ECM, Liu V, et al. Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus. Cell. 1995;80:431-7.



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.



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.

Resources

Human Growth Foundation

997 Glen Cove Avenue

Suite 5

Glen Head, NY 11545

Tel: (516)671-4041

Fax: (516)671-4055

Tel: (800)451-6434

Email: hgf1@hgfound.org

Internet: http://www.hgfound.org/



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

One AMS Circle

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



Cleft Lip and Palate Association

Green Man Tower First Floor

332B Goswell Road

London, EC1V 7LQ

United Kingdom

Tel: 02078334883

Fax: 02078335999

Email: info@clapa.com

Internet: http://www.clapa.com



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

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.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.