Marshall Syndrome

Marshall Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Marshall Syndrome 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

  • deafness-myopia-cataract-saddle nose, Marshall type

Disorder Subdivisions

  • None

General Discussion

Marshall syndrome is a rare autosomal dominant genetic disorder caused by mutations in the COL11A1 gene. Major symptoms may include a distinctive face with a flattened nasal bridge and nostrils that are tilted upward, widely spaced eyes, nearsightedness, cataracts and hearing loss.

Symptoms

Patients with Marshall Syndrome have a distinctive flat sunken midface with a flattened nasal bridge (saddle nose), nostrils that turn upward, and a wide space between the eyes (hypertelorism). The domelike upper portion of the skull (calvaria) is thicker than normal and calcium deposits can be found in the skull (cranium). Eye defects found in patients with Marshall Syndrome are nearsightedness, a disease of the eye in which the lens loses its clarity (cataract), and a wide space between the eyes making the eyeballs appear to be larger than normal. Hearing loss may range from slight to severe; the distortion of the sound is a consequence of the nerve damage (sensorineural). Other symptoms exhibited by some patients with Marshall Syndrome are: crossed eyes (esotropia), a condition in which the line of vision is higher in one eye than the other (hypertropia), retinal detachment, glaucoma, protruding upper incisors (teeth) and a smaller than normal or missing nasal bone.

Causes

Marshall syndrome is a rare autosomal dominant genetic disorder caused by mutations in the collagen XI, alpha-1 polypeptide (COL11A1) gene located on chromosome 1p21.1. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular 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. The risk is the same for males and females.

Affected Populations

Marshall Syndrome affects males and females in equal numbers.

Standard Therapies

Plastic surgery can improve saddle nose in Marshall syndrome. Other surgical procedures are used to remove the lenses of eyes affected by cataracts, after which lens implants are used as replacements. Subsequently, contact lenses may help improve sharpness of vision. Laser techniques are used to loosen any material, such as the cornea or the lens capsule that may adhere to the lens. The use of a hearing aid may be beneficial in some cases. Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

After the removal of the affected lens in children with congenital cataracts, an intraocular lens (IOL) may be implanted. If technically feasible, the IOL is implanted in the lens capsule. More research is needed before this implantation can be used more generally to preserve vision and reduce double vision. 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 Marshall syndrome:



Ruth Liberfarb, MD, PhD

Stickler Syndrome Clinic/ Genetics Clinic-Yawkey 6, MGH

Genetics Unit, Massachusetts General Hospital for Children

175 Cambridge Street-5th floor

Boston, MA 02114

Phone: 617-726-1561

Email: rliberfarb@partners.org

References

TEXTBOOKS

Traboulsi EI. Ed. A Compendium of Inherited Disorders and the Eye. Oxford University Press. New York, NY. 2006:173-174.



Castriota-Scanderbeg A, Dallapiccola B, Eds. Abnormal Skeletal Phenotypes: From Simple Signs to Complex Diagnoses. Springer, New York, NY; 2005:902.



Cassidy S, Allanson J. Eds. Clinical Management of Common Genetic Syndromes. 2nd ed. Wiley Liss, New York, N.Y. 2005:539-541.



Gorlin RJ, Cohen MMJr, Hennekam RCM. Eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:351-353.



Jones KL. Ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:318-319.



JOURNAL ARTICLES

Majava M, Hoornaert K, Bartholdi D, et al. A report on 10 new patients with

Heterozygous mutations in the COL11A1 Gene and a review of Genotype-Phenotype Correlations in Type XI collagenopathies. Am J Med Genet. 2007; 143 A: 258-264.



Van Camp G, Snoeckx RL, Hilgert N, et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Med Genet. 2006;79:449- 456.



Rose PS, Levy HP, Liberfarb RM, et al. Stickler syndrome: clinical characteristics and diagnostic criteria. Am J Med Genet. 2005;138A:199-207.



Poulson AV, Hooymans JMM, Richards AJ, et al. Clinical features of type 2 Stickler syndrome. J Med Genet. 2004;41:3107.



Liberfarb RM, Levy HP, Rose PS, et al. The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genet Med. 2003;5:21-27.



Annunen s, Korkko J, Czarny M et al. Splicing Mutations of 54 - bp Exons in the COL11A1 Gene Cause Marshall Syndrome but Other Mutations Cause Overlapping Marshall/ Stickler Phenotypes. Am J Med Genet. 1999; 65: 974-983.



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



INTERNET

Robin NH, Moran RT, Warman M, Ala-Kokko, L. Updated:November 3, 2011. Stickler Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://www.genetests.org.



McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:154780; Last Update:10/7/11. Available at:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=108300 . Accessed on: January 18, 2012.

Resources

Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240

USA

Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643

Email: contactCCA@ccakids.com

Internet: http://www.ccakids.com



Let's Face It

University of Michigan, School of Dentistry / Dentistry Library

1011 N. University

Ann Arbor, MI 48109-1078

USA

Tel: (360)676-7325

Email: faceit@umich.edu

Internet: http://www.dent.umich.edu/faceit



American Society for Deaf Children

800 Florida Avenue NE

2047

Washington, DC 20002-3695

Tel: (866)895-4206

Fax: (410)795-0965

Tel: (800)942-2732

Email: asdc@deafchildren.org

Internet: http://www.deafchildren.org



NIH/National Eye Institute

31 Center Dr

MSC 2510

Bethesda, MD 20892-2510

United States

Tel: (301)496-5248

Fax: (301)402-1065

Email: 2020@nei.nih.gov

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



National Foundation for Facial Reconstruction

333 East 30th Street, Lobby Unit

New York, NY 10016

Tel: (212)263-6656

Fax: (212)263-7534

Internet: http://www.nffr.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



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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