Coffin Lowry Syndrome

Coffin Lowry Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Coffin Lowry 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

  • Coffin Syndrome
  • Mental Retardation with Osteocartilaginous Abnormalities

Disorder Subdivisions

  • None

General Discussion

Coffin-Lowry syndrome is a rare genetic disorder characterized by mental retardation; abnormalities of the head and facial (craniofacial) area; large, soft hands with short, thin (tapered) fingers; short stature; and/or various skeletal abnormalities. Characteristic facial features may include an underdeveloped upper jawbone (maxillary hypoplasia), an abnormally prominent brow, downslanting eyelid folds (palpebral fissures), widely spaced eyes (hypertelorism), large ears, and/or unusually thick eyebrows. Skeletal abnormalities may include abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis) and unusual prominence of the breastbone (sternum) (pectus carinatum). Coffin-Lowry syndrome is caused by mutations in the RSK2 gene and is inherited as an X-linked dominant genetic trait. Males are usually more severely affected than females.

Symptoms

The symptoms of Coffin-Lowry syndrome tend to be more severe in males, although symptoms in affected females can range from none to the same severity seen in males. The characteristic facial features seen in affected males become more easily identifiable in late childhood and adulthood. The face is characterized by a prominent forehead and eyebrows, narrowing of both temples, scarce hair on the scalp, thickened eyebrow ridges, downslanting eyelid slits, wide-set eyes, thickened upper eyelids, a broad nasal bridge with a thick dividing cartilage (septum), thick prominent lips, an open mouth, prominent chin and ears.



Limb abnormalities may include large soft hands with double-jointed thick fingers that taper toward the tips, an unusual prominent transverse crease (hypothenar) and a shortened big toe. In males, the skin is loose and may stretch easily. Many bone abnormalities may also occur such as thickening of facial bones, shortening of the long bones, and pointed or sunken breast bone. Abnormal front-to-back and side-to-side curvature of the spine may also be present (kyphosis and scoliosis) and progresses with age. Affected individuals usually have short stature. A smaller than average head size (microcephaly) and dental abnormalities are common. Hearing loss is sometimes associated with Coffin-Lowry syndrome. In rare cases, vision loss may occur. Heart problems may be present and can be life threatening.



Affected males may have severe to profound mental retardation. Intelligence in affected females ranges from normal to profound mental retardation. Severely affected children may have no speech development.



Some affected individuals experience episodes of brief collapse without loss of conciousness (drop attacks) that occur following an unexpected noise or emotional event.

Causes

Coffin-Lowry syndrome is caused by changes (mutations) in the RSK2 and RPS6KA3 gene on the X chromosome and has been mapped to Xp22.2-p22.1. Some individuals with Coffin-Lowry syndrome do not have a detectable mutation in the RSK2 gene.



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered 1-22 and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further subdivided into many bands that are numbered. For example, "chromosome Xp22.2-p22.2" refers to band 22.2-22.1 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.



Coffin-Lowry syndrome is inherited as an X-linked dominant genetic trait. About 70-80% of those affected have no family history of the condition. Males with an RSK2 gene mutation will be affected with Coffin-Lowry syndrome and females with an RSK2 gene mutation have a high risk for developmental delay and mild physical symptoms of the disease.

Affected Populations

Coffin-Lowry syndrome affects as many males as females. However, symptoms may be more severe in males.

Standard Therapies

Diagnosis

X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin-Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin-Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.



Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin-Lowry syndrome because not all affected individuals have a detectable mutation.



Treatment

Treatment for Coffin-Lowry syndrome is symptomatic and supportive. Affected individuals should have regular cardiac, hearing and visual examinations. Patients should be monitored for progressive kyphoscoliosis which can be life threatening if the cardiorespiratory system becomes compromised. Antiepileptic medications such as clonazepam may be used to treat drop attacks.



Genetic counseling will be helpful for patients and their families.

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

Harum KH and Johnson MV. Coffin-Lowry syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:171-172.



Hunter AGW, Schwartz CE and Abidi F, (updated 16 July 2002). Coffin-Lowry Syndrome In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.genetests.org Accessed 8/03.



ARTICLES

Delaunoy JP, Abidi F, Zeniou M, et al. Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. Hum Mutat 2001;17:103-116.



Gilgenkrantz S, Mujica P, Gruet P, et al. Coffin-Lowry syndrome: a multicenter study. Clin Genet 1988;34:230-245.



Stevenson RE, Schwartz CE, Schroer RJ. X-linked mental retardation. New York: Oxford University Press, 2000.



Hanauer A, Young ID. Coffin-Lowry syndrome: clinical and molecular features. J Med Genet. 2002;39:705-13.



Bird H, et al. Crossover analysis in a British family suggests that Coffin-Lowry syndrome maps to a 3.4-cM interval in Xp22. Am J Med Genet. 1995;59:512-6.



Trivier E, et al. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature. 1996;384:567-70.



Biancalana V, et al. Confirmation and refinement of the genetic localization of the Coffin-Lowry syndrome locus in Xp22.1-p22.2. Am J Med Genet. 1992;50:981-7.



Vles JS, et al. Early clinical signs in Coffin-Lowry syndrome. Clin Genet. 1984;26:448-52.



Hersh JH, et al. Forearm fullness in Coffin-Lowry syndrome: a misleading yet possible early diagnostic clue. Am J Med Genet. 1984;18:195-9.



Wilson WG, et al. Brief clinical report: early recognition of the Coffin-Lowry syndrome. Am J Med Genet. 1981;8:215-20.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:303600; Last Update:9/18/2002.

Resources

The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



Coffin-Lowry Syndrome Foundation

675 Kalmia Pl NW

Issaquah, WA 98027

Tel: (425)427-0939

Email: CoffinLowry@gmail.com

Internet: http://www.clsf.info



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 of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

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



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/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.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.