Jackson-Weiss Syndrome (JWS) is a rare genetic disorder characterized by distinctive malformations of the head and facial (craniofacial) area and abnormalities of the feet. The range and severity of symptoms and findings may be extremely variable, including among affected members of the same family (kindred). However, primary findings may include premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), unusually flat, underdeveloped midfacial regions (midfacial hypoplasia) abnormally broad great toes, and/or malformation or fusion of certain bones within the feet. In some cases, Jackson-Weiss Syndrome may result from new genetic changes (mutations) that appear to occur randomly for unknown reasons (sporadically). In other affected individuals, the disorder may be inherited as an autosomal dominant trait.
Jackson-Weiss Syndrome (JWS) is typically characterized by craniofacial malformations occurring in association with skeletal abnormalities of the feet. However, some cases have been reported in which affected individuals have no craniofacial abnormalities. Therefore, evidence suggests that the range and severity of associated findings may vary greatly among members of the same or other affected families (kindreds).
In those with craniofacial abnormalities, such malformations may result in a distinctive facial appearance. For example, there may be premature closure of the fibrous joints (cranial sutures) between particular bones of the skull (craniosynostosis), causing the top of the head to appear pointed or conical (acrocephalic). In some cases, craniosynostosis may be associated with headaches, disturbances in vision, and hydrocephalus, a condition in which there is an abnormal accumulation of cerebrospinal fluid (CSF) in the skull. Hydrocephalus often results in increased fluid pressure and abnormal enlargement of the cavities (ventricles) within the brain.
Individuals with Jackson-Weiss Syndrome may also have additional craniofacial abnormalities. These may include a relatively flat back region of the head (occiput), underdeveloped midfacial regions (midfacial hypoplasia), and widely spaced eyes (ocular hypertelorism). Affected individuals may also have downwardly slanting eyelid folds (palpebral fissures), drooping of the upper eyelids (ptosis), or abnormal deviation of one eye in relation to the other (strabismus). In some cases, additional features may also be present, such as a flat nasal bridge, an underdeveloped upper jawbone (maxillary hypoplasia), a highly arched roof of the mouth (palate), incomplete closure of the palate (cleft palate), and/or malformed ears.
Jackson-Weiss Syndrome may also be characterized by various abnormalities of the feet. For example, affected individuals may have webbed or fused second and third toes (syndactyly) and/or abnormally short, broad great toes that may bend inward (varus deformities). There may also be malformation or fusion of certain bones within the body of the feet (metatarsals), the ankles (tarsal bones), and/or the heels (calcanei). Some individuals with Jackson-Weiss Syndrome may also have additional physical abnormalities, such as limitation of joint movements and/or a condition in which the legs are abnormally curved inward, with the knees close together and the ankles widely separated (genu valgum). In addition, although most individuals with the disorder have average or above average intelligence, varying levels of mental retardation have been reported in a few cases.
In some affected individuals, Jackson-Weiss Syndrome may result from new genetic changes (mutations) that appear to occur randomly for unknown reasons (sporadically). In other cases, the disorder may be inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
Evidence suggests that familial and sporadic cases of Jackson-Weiss Syndrome are caused by mutations of a gene known as FGFR2 that is located on the long arm (q) of chromosome 10 (10q26). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered.
The FGFR2 gene regulates (encodes for) the production of a protein known as a fibroblast growth factor receptor (FGFR). According to researchers, genetic mutations that disrupt the functioning of such proteins may result in certain abnormalities during embryonic development, such as malformations of the craniofacial area and the limbs. A number of syndromes have been identified that are associated with mutations of the FGFR2 gene including Crouzon, Pfeiffer, and Apert Syndromes. (For further information on these disorders, please see the “Related Disorders” section of this report below.)
In most cases, individuals with a mutated gene for Jackson-Weiss Syndrome will have symptoms and findings associated with the disorder (high penetrance). However, in such cases, the characteristics that are manifested may vary greatly in range and severity from case to case (variable expressivity).
Jackson-Weiss Syndrome appears to affect males and females in equal numbers. The disorder was originally described in 1976 (C.E. Jackson) in a large Amish family (kindred). Within this kindred, 88 affected individuals were observed and an additional 50 were known to be affected. Several other families with the disorder have since been described. In addition, isolated cases have been reported in which there was no known family history (sporadic cases). In individuals with Jackson-Weiss Syndrome, the range and severity of associated symptoms may vary greatly, including among members of the same kindred.
In some cases, a diagnosis of Jackson-Weiss Syndrome may be suggested before birth (prenatally) based upon detection of certain characteristic physical findings during fetal ultrasound. During fetal ultrasonography, sound waves are used to create an image of the developing fetus.
The disorder may be diagnosed or confirmed at birth or during early infancy based upon a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests including advanced imaging techniques. For example, specialized x-ray imaging studies, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI), may help to confirm the presence and/or extent of certain craniofacial, foot, or other skeletal abnormalities. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissues. During MRI, a magnetic field and radio waves create cross-sectional images of particular tissues or internal structures.
The treatment of Jackson-Weiss Syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; physicians who specialize in disorders of the skeleton, joints, muscles, and related tissues (orthopedists). physical therapists; and/or other health care professionals.
Specific therapies for Jackson-Weiss Syndrome are symptomatic and supportive. In some affected individuals, craniosynostosis and associated hydrocephalus may result in abnormally increased pressure within the skull (intracranial pressure) and on the brain. In such cases, surgery may be advised to correct craniosynostosis and to insert a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed. Surgery may also be recommended to correct other craniofacial and skeletal abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors. In some cases, physical therapy and additional orthopedic and supportive measures may also be recommended to help improve an affected individual's mobility.
Early intervention may be important to ensure that children with Jackson-Weiss Syndrome reach their potential. Special services that may be beneficial include special education and other medical, social, and/or vocational services.
Genetic counseling will be of benefit for affected individuals and their families. In addition, thorough clinical evaluations may be important in family members of diagnosed individuals to detect any findings that may be associated with Jackson-Weiss Syndrome. Other treatment for this disorder is symptomatic and supportive.
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