Beals Syndrome

Beals Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Beals 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

  • CCA
  • arachnodactyly, contractural Beals type
  • Beals-Hecht syndrome
  • contractural arachnodactyly, congenital

Disorder Subdivisions

  • None

General Discussion

Beals syndrome is an extremely rare genetic disorder characterized by the permanent fixation of certain joints (e.g., fingers, elbows, knees, and hips) in a flexed position (contractures); abnormally long, slender fingers and toes (arachnodactyly); permanently flexed fingers (camptodactyly); and/or abnormally shaped ears resulting in a "crumpled" appearance. In addition, affected individuals may exhibit front-to-back and side-to-side curvature of the spine (kyphoscoliosis); feet that are abnormally positioned (talipes equinovarus or clubfoot); outward displacement of the fingers (ulnar deviation of the fingers); an abnormally short neck; and/or. Rarely, affected individuals may have a slight deformity of the valve on the left side of the heart (mitral valve prolapse). Beals syndrome is inherited as an autosomal dominant trait.

Symptoms

Beals syndrome encompasses a broad range of symptoms. The specific symptoms that develop in each individual case and the severity of symptoms often vary. Most individuals have permanent fixation of certain joints in a flexed position (contractures) that is present a birth (congenital). The joints of the fingers, elbows, knees, and hips are most often affected. In most cases, contractures improve with age.



In some cases, affected infants have abnormally shaped ears giving them a "crumpled" appearance. Additional common symptoms include abnormally long, slender fingers and toes (arachnodactyly), permanently flexed fingers (camptodactyly), underdevelopment of certain muscles (muscular hypoplasia), and front-to-back and side-to-side curvature of the spine (kyphoscoliosis). Kyphoscoliosis is usually progressive and severe, often necessitating surgery.



In some cases, a specific heart defect known as mitral valve prolapse (MVP) may occur. The mitral valve is located between the left upper and left lower chambers (left atrium and left ventricle) of the heart. MVP occurs when one or both of the flaps (cusps) of the mitral valve bulge or collapse backward (prolapse) into the left atrium during ventricular contraction (systole). In some cases, this may allow leakage or the backward flow of blood from the left ventricle back into the left atrium (mitral regurgitation). In some case, no associated symptoms are apparent (asymptomatic). However, in other cases, MVP can result in chest pain, abnormal heart rhythms (arrhythmias), fatigue, dizziness, and/or other symptoms and signs.



Less common symptoms may occur in some cases. Additional abnormalities affecting the head and face (craniofacial) region include an abnormally small jaw (micrognathia), a prominent forehead (frontal bossing), a highly arched palate, a long narrow head (dolichocephaly or scaphocephaly), or an abnormally wide head (brachycephaly). Nearsightedness (myopia) affecting the eyes may also occur.



Some individuals may have an abnormally short neck. In some cases, affected individuals may have a clubbed foot, inwardly clasped (adducted thumbs), and bowed long bones of the arms and leg.



In extremely rare cases, individuals with Beals syndrome may develop a severe form of the disorder associated with life-threatening complications. This severe form of Beals syndrome is associated with various heart and intestinal abnormalities including atrial and ventricular septal defects; improper development of the aorta resulting in blockage of blood flow (interrupted aortic arch); a single umbilical artery; a condition in which the tube (esophagus) that normally carries food from the mouth to the stomach narrows to a thin cord or ends in a pouch rather than providing passage to the stomach (esophageal atresia); abnormal closure or blockage of the first part of the small intestine (duodenal atresia); and obstruction of the intestines due to malformation of part of the intestines (intestinal malrotation).



In extremely rare cases, Beals syndrome may be associated with aortic root dilatation, a condition characterized by widening (dilatation) of the opening where the aorta and the heart chamber connect (aortic root).

Causes

Beals syndrome is inherited as an autosomal dominant 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.



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 Beals syndrome occurs due to disruptions or changes (mutations) to the fibrillin-2 (FBN2) gene located on the long arm of chromosome 5 (5q23-31). 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 5q23-31" refers to bands 23-31 on the long arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Beals syndrome affects males and females in equal numbers. The prevalence of Beals syndrome is unknown. For years, researchers speculated that Marfan syndrome (another rare connective tissue disorder) and Beals syndrome may be the same disorder because of the overlap of clinical symptoms. However, investigators have determined these disorders are caused by mutations to different genes confirming that Beals syndrome is a distinct disorder.



Because of the similarities with the more recognized Marfan syndrome, it is difficult to determine the true incidence of Beals syndrome in the general population. However, molecular genetic testing can confirm a diagnosis of Beals syndrome and should allow researchers to obtain a more accurate idea of its incidence in the future.

Standard Therapies

Diagnosis

A diagnosis of Beals syndrome is suspected based upon a thorough clinical evaluation and identification of characteristic findings. A diagnosis may be confirmed by molecular genetic testing which detects FBN-2 mutations in approximately 75 percent of cases.



Treatment

The treatment of Beals syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, orthopedists, and other health care professionals may need to systematically and comprehensively plan an affect child's treatment.



Physical therapy, often started during childhood, may be used to treat joint contractures. Physical therapy can improve joint mobility and lessen the effects of muscular hypoplasia. In many cases, joint contractures improve without treatment (spontaneously) as individuals grow older. However, in some cases, surgery may be necessary to treat contractures. Kyphoscoliosis is often progressive and severe and may necessitate treatment with braces or surgery.



Many physicians recommend that individuals with Beals syndrome receive an echocardiogram to distinguish the disorder from Marfan syndrome and detect any heart defects that may potentially be associated with the disorder. During an echocardiogram, high-frequency sound waves are used to create a structural image of the heart and nearby tissue.



A thorough eye (ophthalmologic) examination is recommended to detect any potential eye abnormalities that are sometimes associated with Beals syndrome. 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

Harris EDJr, Budd RC, Firestein GS, et al., eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005:1568.



Godfrey M. Congenital Contractural Arachnodactyly. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:3.



Rimoin D, Connor JM, Pyeritz RP, Korf BR, eds. Emory and Rimoin's Principles and Practice of Medical Genetics. 4th ed. New York, NY: Churchill Livingstone; 2002:4013.



Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co.; 1997:476.



JOURNAL ARTICLES

Tuncbilek E, Alanay Y. Congenital contractural arachnodactyly (Beals syndrome). Orphanet J Rare Dis. 2006;1:20.



Gupta PA, Wallis DD, Chin TO, et al. FBN2 mutation associated with manifestations of Marfan syndrome and congenital contractural arachnodactyly. J Med Genet. 2004;41:e56.



Gupta PA, Putnam EA, Carmical SG, et al. Ten novel FBN2 mutations in congenital contractural arachnodactyly: delineation of the molecular pathogenesis and clinical phenotype. Hum Mutat. 2002;19:39-48.



Maslen C, Babcock D, Raghunath M, Steinmann B. A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly. Am J Hum Genet. 1997;60:1389-98.



Bamshad M, Jorde LB, Carey JC. A revised and extended classification of the distal arthrogryposes. Am J Med Genet. 1996;65:277-81.



Bawle RK, Hecht F. Ectopia lentis and aortic root dilatation in congenital contractural arachnodactyly. Am J Med Genet. 1992;42:19-21.



Lee B, Godfrey M, Vitale E, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991;352:330-4.



Beals RK, Hecht F. Congenital contractural arachnodactyly: a heritable disorder of connective tissue. J Bone Joint Surg. 1971;53A:987-93.



INTERNET

Godfrey M. (Updated February 23, 2012). Congenital Contractural Arachnodactyly. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed May 3, 2012.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Arthrogryposis, Distal, Type 9; DA9. Entry No: 121050. Last Edited September 20, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed May 3, 2012.

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



National Marfan Foundation

22 Manhasset Avenue

Port Washington, NY 11050

Tel: (516)883-8712

Fax: (516)883-8040

Tel: (800)862-7326

Email: staff@marfan.org

Internet: http://www.marfan.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/



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



Cleft Lip and Palate Foundation of Smiles

2044 Michael Ave SW

Wyoming, MI 49509

Tel: (616)329-1335

Email: Rachelmancuso09@comcast.net

Internet: http://www.cleftsmile.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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