NORD gratefully acknowledges Maurice Godfrey, PhD, University of Nebraska Medical Center, for assistance in the preparation of this report.
CCA 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.
Some 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.
Some children have a specific heart defect known as mitral valve prolapse (MVP). 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 children. 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.
Rarely, individuals with CCA may develop a severe form of the disorder associated with life-threatening complications. This severe form of CCA 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).
Rarer still, CCA 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).
CCA occurs due to disruptions or changes (mutations) to the fibrillin-2 (FBN2) gene.
CCA is inherited in an autosomal dominant pattern. 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 mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
CCA affects males and females in equal numbers. The prevalence of CCA is unknown. For years, researchers speculated that the Marfan syndrome (another rare connective tissue disorder) and CCA may be the same disorder because of the overlap of clinical symptoms. However, investigators have determined these disorders are caused by mutations in different genes confirming that CCA is a distinct disorder.
Because of the similarities with the more recognized Marfan syndrome, it is difficult to determine the true incidence of CCA in the general population. However, molecular genetic testing can confirm a diagnosis of CCA and should allow researchers to obtain a more accurate idea of its incidence in the future.
The recent identification of another condition with overlapping symptoms, Loeys-Dietz Syndrome has led to additional misdiagnosis (see below).
A diagnosis of CCA 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 gene mutations in approximately 75 percent of patients.
CCA has also been recognized via prenatal ultrasound. Preimplantation genetic diagnosis has also been used successfully in an affected family.
The treatment of CCA 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 CCA 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 CCA.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
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Harris EDJr, Budd RC, Firestein GS, et al., eds. Kelley’s Textbook of Rheumatology. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005:1568.
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.
Paterick TE, Humphries JA, Ammar KA, et al. Aortopathies: etiologies, genetics, differential diagnosis, prognosis and management. Am J Med 2013;126:670.
Davis MR, Summers KM. Structure and function of the mammalian fibrillin gene family: implications for human connective tissue diseases. Mol Genet Metab. 2012;107:635.
Callewaert BL, Loeys BL, Ficcadenti A, et al. Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: report of 14 novel mutations abd review of the literature. Hum Mutat 2009; 30:334.
Frédéric MY, Monino C, Marschall C, et al. The FBN2 gene: new mutations, locus-specific database (Universal Mutation Database FBN2) and genotype-phenotype correlations. Hum Mutat 2009; 30:181
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.
Chen L, Diao Z, Xu Z, Zhou J, Wang W, Li J, Yan G, Sun H. The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy. J Assist Reprod Genet. 2016 Nov; 33(11):1459-1466
Lavillaureix A, Heide S, Chantot-Bastaraud S, Marey I, Keren B, Grigorescu R, Jouannic JM, Gelot A, Whalen S, Héron D, Siffroi JP. Mosaic intragenic deletion of FBN2 and severe congenital contractural arachnodactyly. Clin Genet. 2017 Nov; 92(5):556-55
Takeda N, Morita H, Fujita D, Inuzuka R, Taniguchi Y, Imai Y, Hirata Y, Komuro I. Congenital contractural arachnodactyly complicated with aortic dilatation and dissection: Case report and review of literature. Am J Med Genet A. 2015 Oct; 167A (10):2382-7
Inbar-Feigenberg M, Meirowitz N, Nanda D, Toi A, Okun N, Chitayat D. Beals syndrome (congenital contractural arachnodactyly): prenatal ultrasound findings and molecular analysis. Ultrasound Obstet Gynecol. 2014 Oct; 44(4):486-90.
Paterick TE, Humphries JA, Ammar KA, Jan MF, Loberg R, Bush M, Khandheria BK, Tajik AJ. Aortopathies: etiologies, genetics, differential diagnosis, prognosis and management. Am J Med. 2013 Aug; 126 (8):670-8
Woolnough R, Dhawan A, Dow K, Walia JS. Are Patients With Loeys-Dietz Syndrome Misdiagnosed With Beals Syndrome? Pediatrics. 2017 Mar; 139(3).
Godfrey M. Congenital Contractural Arachnodactyly. 2001 Jan 23 [Updated 2012 Feb 23]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1386/ Accessed July 31, 2018.
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://omim.org/entry/121050 Accessed July 31, 2018.
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