Cutis Laxa

Cutis Laxa

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Cutis Laxa 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

  • Chalasodermia, Generalized
  • Chalazodermia, Generalized
  • Dermatochalasia, Generalized
  • Dermatolysis, Generalized
  • Dermatomegaly
  • Elastorrhexis, Generalized
  • Occipital Horn Syndrome

Disorder Subdivisions

  • Congenital Cutis Laxa Syndrome
  • Acquired Cutis Laxa Syndrome
  • Cutis Laxa , X-linked (formerly known as Ehlers Danlos IX)
  • Cutis Laxa, X-linked (formerly known as Ehlers Danlos IX)

General Discussion

Cutis laxa is rarely encountered and may occur in several inherited (congenital) forms or come about in the course of another disorder (acquired). It is a connective tissue disorder characterized by skin that is loose (lax), hanging, wrinkled, and lacking in elasticity (hyperelasticity). The affected areas of skin may be thickened and dark. In addition, the joints are loose (hypermobility) because of lax ligaments and tendons. The disorder involves a variety of symptoms and signs that result from defects in connective tissue. Defective connective tissue may cause problems in the vocal cords, bones, cartilage, blood vessels, bladder, kidney, digestive system, and lungs.



Four separate inherited forms of this disorder have been identified. Most cases are inherited as one or another of two types of autosomal recessive inheritance. However, cases of autosomal dominant inheritance have been reported, as well as a form that is credited to X-linked inheritance.

Symptoms

Congenital cutis laxa is typically diagnosed at birth or during the first few months of life. Children with the characteristic sagging skin appear to be depressed, melancholic, and sad. The disorder presents with great variability. As many as 80 different symptoms and signs have been described.



The symptoms of autosomal recessive cutis laxa type 1 include: lax and dislocated joints, retarded growth, difficulty in breathing (emphysema), unnatural sacs or pouches (diverticulum) in the linings of the duodenum, bladder and/or esophagus; twisted, winding (tortuous) arteries; and hernias, as well as an enzyme deficiency (lysyl oxidase). Lysyl oxidase is key to the development of properly functioning connective tissue.



The symptoms of autosomal recessive cutis laxa type 2 include: loose skin, bone abnormalities, joint dislocations, curvature of the spine, tooth decay, and delayed closure of the cranial sutures.



The symptoms of autosomal dominant cutis laxa include: loose skin, loose skin, missing elastic fibers, premature aging (progeria), breathing difficulties (emphysema).



The symptoms of X-linked cutis laxa include: mild mental retardation, loose skin and joints, bone abnormalities (such as hooked nose, pigeon breast, or funnel breast), blockages in the ureter or urethra, fluid loss because of loose stools, and lysyl oxidase deficiency.



The acquired form of cutis laxa may develop slowly and may not appear until puberty or later during early adulthood. It tends to follow illnesses in which fever is severe, or skin rashes are intense (erythema multiforme) or inflammation is strong. Also, the acquired form may be an autoimmune condition or the result of an injury to the nerves that control the widening or opening (dilation) of the blood vessels.



Episodes of abnormal swelling (transient angioedema), especially in the face and neck, and inflammation are frequently the first signs of the acquired form of the disease. Skin changes develop slowly and may be widespread or localized to the face, trunk, and/or neck. Small blood vessels under the skin in these affected areas may rupture easily and produce purplish-red spots (purpura) on the skin. Life-threatening complications may occur in some cases of acquired cutis laxa including rupture of the major blood vessel carrying blood away from the heart (aorta), respiratory insufficiency due to the loss of elasticity of the lungs (emphysema), and/or digestive difficulties. The severity of the acquired form of cutis laxa is determined by the intensity, progression, and pulmonary complications of the disorder.

Causes

Four genetic forms of cutis laxa are recognized. These are: two types of autosomal recessive forms (types 1 and 2), one autosomal dominant form, and one sex-linked or X-linked form.



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 14q32.1" refers to band 32.1 on the long arm of chromosome 14. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Cutis laxa recessive, type 1, is inherited as an autosomal recessive genetic trait. The responsible genes have been mapped to Gene Map Locus: 14q32.1, 5q23.3-q31.2.



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.



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.



The most rare form of cutis laxa is inherited as an autosomal dominant genetic trait. The gene responsible for this autosomal dominant form has been mapped to Gene Map Locus: 7q11.2.



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.



The congenital form of cutis laxa is usually more severe when it is inherited as an autosomal recessive trait. When inherited as an autosomal dominant trait, the skin problems may be minimal (cosmetic).



An X-linked recessive form of cutis laxa has also been classified as Ehlers-Danlos Type IX. There is disagreement in the medical literature as to the classification of this form of the disease. Ehlers-Danlos syndrome is a disorder of connective tissue, of which there are several sub-types (see Related Disorders section of this report). The gene responsible for the X-linked form of the disorder has been mapped to Gene Map Locus: Xq12-q13.



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 "turned off" and all 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. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". 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 males always pass their Y chromosome instead of their X chromosome to 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% to have a son affected with the disease, and a 25% chance to have an unaffected son.



The acquired form of cutis laxa may develop following a severe illness involving fever, inflammation of membranes that produce serous fluid (polyserositis), and/or the rare skin disorder erythema multiforme. Some research suggests that acquired cutis laxa may be the result of an autoimmune process in the body. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons.

Affected Populations

Cutis laxa is a rare skin disorder that affects males and females in equal numbers. Only a few hundred (or fewer) cases have been reported in the medical literature worldwide. Inherited forms of cutis laxa occur more often than the acquired form.

Standard Therapies

Diagnosis

The diagnosis is obvious. The identification of the type of cutis laxa involves studying the chemical activity of cells (cytochemical analysis) to determine the gene involved.



Treatment

There is no specific treatment for people with cutis laxa. Plastic surgery usually improves the cosmetic appearance of individuals with the disorder. The surgery may be less successful in those people with the acquired form of the disease. Other surgical procedures may be considered for correction of intestinal diverticula, hernias, and/or other complications. In some affected individuals, treatment may be limited to appropriate therapy for any heart, respiratory, or other complications that may develop.



Genetic counseling may be of benefit for people with cutis laxa 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

Berkow R, ed. The Merck Manual-Home Edition. 2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1610.



Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996



Champion RH, Burton JL, Ebling FJG. Eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992.



REVIEW ARTICLES

Gupta A, Helm TN. Acquired cutis laxa associated with multiple myeloma. Cutis. 2002;69:114-18.



Milewicz DM, Urban Z, Boyd C. Genetic disorders of the elastic fiber system. Matrix Biol. 2000;19:471-80.



Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998;1:85-98.



JOURNAL ARTICLES

Rodriguez-Revenga L, et al. A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa. Arch Dermatol. 2004;140:1135-9.



De Schepper S, et al. Cutis laxa of the autosomal recessive type in a consanguineous family. Eur J Dermatol. 2003;13:529-33.



Wong MC, Georgeu GA, Sassoon EM, et al. A case report of cutis laxa in one of identical twins. Aesthetic Plast Surg. 2002;26:486-89.



Andiran N, Sarikayalar F, Saraclar M, et al. Autosomal recessive form of congenital cutis laxa: more than the clinical appearance. Pedatr Dermatol. 2002;19:412-14.



Loeys B, Van Maldergem L, Mortier G, et al. Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet. 2002;11:2113-18.



Dicker TJ, Morton J, Williamson RM, et al. Myeloma-associated systemic amyloidosis presenting with acquired digital cutis laxa-like changes. Australas J Dermatol. 2002;43:144-46.



Nakamura T, Lozano PR, Ikeda Y, et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature. 2002;415:171-75.



Yanagisawa H, Davis EC, Starcher BC, et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature. 2002;415:168-71.



Palmer CA, Percy AK. Neuropathology of occipital horn syndrome. J Child Neurol. 2001;16:764-66.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Cutis Laxa. [Recessive 1] The Johns Hopkins University. Entry Number; 219100: Last Edit Date; 2/27/2003.



McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Cutis Laxa with Growth and Development Delay. [Recessive 2] The Johns Hopkins University. Entry Number; 219200: Last Edit Date; 8/2/1999.



McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Cutis Laxa. [Dominant] The Johns Hopkins University. Entry Number; 123700: Last Edit Date; 1/6/1999.



McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Cutis Laxa, X-Linked. The Johns Hopkins University. Entry Number; 304150: Last Edit Date; 11/10/1999.



Molis T. Cutis Laxa (Elastolysis). EMedicine. Last Updated: April12, 2002. 9pp.

www.emedicine.com/derm/topic93.htm



Cutis Laxa Internationale. What is Cutis Laxa? Last Update: 27th January 2003. 3pp

www.orpha.net/nestasso/cutislax/en02-Cutis_Laxa_what_is_it.htm



Cutis Laxa Internationale. Cutis Laxa Worldwide. Last Update: 27th January 2003. 2pp

www.orpha.net/nestasso/cutislax/en03-Cutis_Laxa_worldwide.htm



Blanchet-Bardon C. Cutis laxa. Orphanet. nd. 1p.

www.orpha.net/consor/cgi-bin/Pages.php



Cutis laxa: List of Clinical Signs. nd. 2pp.

www.orpha.net/consor/cgi-bin/Pages.php

Resources

American Autoimmune Related Diseases Association, Inc.

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Tel: (586)776-3900

Fax: (586)776-3903

Tel: (800)598-4668

Email: aarda@aarda.org

Internet: http://www.aarda.org/



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

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USA

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Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

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



Cutis Laxa Internationale

122 Clos des Ecoliers

Saint Cergues, 74140

France

Tel: 330456302188

Fax: 330456302188

Email: mcjlboiteux@aol.com

Internet: http://www.orpha.net/nestasso/cutislax



Genetic and Rare Diseases (GARD) Information Center

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Tel: (888)205-2311

TDD: (888)205-3223

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



Madisons Foundation

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Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



AutoImmunity Community

Email: moderator@autoimmunitycommunity.org

Internet: http://www.autoimmunitycommunity.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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