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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.
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).
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.
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.
Symptoms of the following disorders can be similar to those of Beals Syndrome. Comparisons may be useful for a differential diagnosis:
Arthrogryposis multiplex congenita is a rare congenital disease characterized by reduced mobility of multiple joints at birth due to proliferation of fibrous tissue. Symptoms of this disorder may be: a fixed range of motion of joints; shoulders that are bent inward and internally rotated; wrists and fingers that are bent and muscles that are underdeveloped. (For more information on this disorder, choose "Arthrogryposis Multiplex Congenita" as your search term in the Rare Disease Database.)
Marfan syndrome is an inherited disorder of the connective tissue. It is characterized by unusually thin, long, limbs, feet and fingers, an unusual limberness of the joints, a relaxation of the muscles, a progressive curvature of the spine, a protruding or indented breastbone and flat feet. Enlargement and degeneration of the aorta, mitral valve prolapse and the possibility of an aortic aneurysm are serious consequences of Marfan Syndrome. (For more information on this disorder, choose "Marfan Syndrome" as your search term in the Rare Disease Database.)
Gordon syndrome is an extremely rare disorder that belongs to a group of genetic disorders known as the distal arthrogryposes. These disorders typically involve stiffness and impaired mobility of certain joints of the lower arms and legs (distal extremities) including the knees, elbows, wrists, and/or ankles. These joints tend to be permanently fixed in a bent or flexed position (contractures). Gordon syndrome is characterized by the permanent fixation of several fingers in a flexed position (camptodactyly), abnormal bending inward of the foot (clubfoot or talipes), and, less frequently, incomplete closure of the roof of the mouth (cleft palate). In some cases, additional abnormalities may also be present. The range and severity of symptoms may vary from case to case. Gordon syndrome is inherited as an autosomal dominant trait. (For more information on this disorder, choose "Gordon" as your search term in the Rare Disease Database.)
Homocystinuria is a rare metabolic condition characterized by an excess of the compound homocystine in the urine. The condition may result from deficiency of any of several enzymes involved in the conversion of the essential amino acid methionine to another amino acid (cysteine)--or, less commonly, impaired conversion of the compound homocysteine to methionine. Enzymes are proteins that accelerate the rate of chemical reactions in the body. Certain amino acids, which are the chemical building blocks of proteins, are essential for proper growth and development. In most cases, homocystinuria is caused by reduced activity of an enzyme known as cystathionine beta-synthase (CBS). Due to deficiency of the CBS enzyme, affected infants fail to grow and gain weight at the expected rate (failure to thrive) and have developmental delays. By approximately age three, additional, more specific symptoms and findings may become apparent. These may include partial dislocation (subluxation) of the lens of the eyes (ectopia lentis), associated "quivering" (iridodonesis) of the colored region of the eyes (iris), severe nearsightedness (myopia), and other eye (ocular) abnormalities. Although intelligence may be normal in some cases, many children may be affected by progressive mental retardation. In addition, some may develop psychiatric disturbances and/or episodes of uncontrolled electrical activity in the brain (seizures). Affected individuals also tend to be thin with unusually tall stature; long, slender fingers and toes (arachnodactyly); and elongated arms and legs ("marfanoid" features). Additional skeletal abnormalities may include progressive sideways curvature of the spine (scoliosis), abnormal protrusion or depression of the breastbone (pectus carinatum or excavatum), and generalized loss of bone density (osteoporosis). In addition, in those with the disorder, blood clots may tend to develop or become lodged within certain large and small blood vessels (thromboembolisms), potentially leading to life-threatening complications. (For more information on this disorder, choose "homocystinuria" as your search term in the Rare Disease Database.)
Stickler syndrome refers to a group of disorders of the connective tissue that involves several of the body’s organ systems such as the eye, skeleton, inner ear, and/or the head and face. Connective tissue is made up of a protein known as collagen that develops into the several varieties found in the body. It is the tissue that physically supports many organs in the body and may act like glue or an elastic band that allows muscles to stretch and contract. Stickler syndrome often affects the connective tissue of the eye, especially in the interior of the eyeball (vitreous humor), and the ends of the bones that make up the joints of the body (epiphysis). Most authorities agree that there are four types of Stickler syndrome, of which three are reasonably well differentiated and a fourth remains not well understood. Stickler syndrome type I (STL1) is responsible for about 75% of reported cases and presents with a full array of symptoms (eye, ear, jaw and cleft, joints); Stickler syndrome type II; (STL2) also presents with a full array of symptoms; Stickler syndrome type III (STL3) presents with a "Stickler-like" syndrome that affects the joints and hearing without involving the eyes. Some researchers believe that this form is the same disorder as heterozygous oto-spondylo-megaepiphyseal dysplasia (OSMED). (For more information on this disorder, choose "Stickler" as your search term in the Rare Disease Database.)
The following disorders may occur in conjunction with Beals Syndrome:
Keratoconus is a slowly progressive enlargement of the curved transparent outer layer of fibrous tissue covering the eyeball (cornea). The resulting conical shape of the cornea causes blurred vision and other vision problems. Inherited forms of this disorder usually begin after puberty. Keratoconus can also occur in conjunction with a variety of other disorders.
Mitral valve prolapse syndrome is a heart disorder. The exact cause is unknown. It can be a symptom of other disorders such as connective tissue diseases or muscular dystrophy, or it may occur by itself. Major symptoms include chest pain and/or palpitations, accompanied by a heart murmur. Shortness of breath, fatigue, lightheadedness and dizzy spells, in some cases, progress to an inability to breathe except when sitting in an upright position, can be experienced. There is a characteristic click heard through a stethoscope upon physical examination. Blood may flow back through the heart valve (mitral regurgitation) causing other complications.
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.
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.
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Report last updated: 2012/06/19 00:00:00 GMT+0