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.
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 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 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 CCA 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.
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.
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 mutations in approximately 75 percent of cases.
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 may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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