Jackson-Weiss syndrome

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Jackson-Weiss syndrome


Jackson-Weiss syndrome (JWS) is a hereditary disease of varying severity affecting the skull, the face, and the feet. JWS is inherited in an autosomal dominant manner.


Jackson-Weiss syndrome is characterized by a small midface, unusual skull shape, and foot abnormalities. The feet display very wide big toes and webbing of the skin between the second and third toes. Additionally, the toes are angled inward. Bony foot defects apparent on x ray include short, wide foot bones and fusion of some of the foot and ankle bones.

The hallmark skull differences associated with JWS are caused by the premature closure of skull sutures, or skull plates. Other features include a small jaw, flattening of the nasal bridge and the middle third of the face, and a beaked nose. The eyes may be crossed and are widely set and slanting downward with droopy eyelids. High arching of the roof of the mouth or cleft palate, an incomplete closure of the roof of the mouth, may also be present. Mental retardation has been reported in some individuals with JWS.

Genetic profile

Jackson-Weiss syndrome is inherited in an autosomal dominant manner. This means that possession of only one copy of the defective gene is enough to cause disease. When a parent has Jackson-Weiss syndrome each of his or her children have a 50% chance to inherit the disease-causing mutation. JWS is believed to have a high rate of penetrance. This means that almost all people who inherit the altered gene will manifest symptoms. JWS has also occurred spontaneously in babies with no family history of it or any similar disorder. This is known as a sporadic occurrence.

JWS has been associated with changes in two different fibroblast growth factor receptor genes, the FGFR1 and FGFR2 genes. The fibroblast growth factor receptor genes serve as a blueprint for proteins important in inhibiting growth during and after embryonic development. FGFR1 is located on human chromosome 8 in an area designated as 8p11.2-p11.1. FGFR2 is located on human chromosome 10 in an area designated as 10q26.

As of 2001, FGFR1 has been associated with JWS in only one reported patient who had an unusual presentation of the disorder. This patient displayed JWS's characteristic toes, foot bone fusion, and short fingers, but only very mild skull and facial differences. The genetic change seen in this patient had been seen before in a patient with symptoms much like Pfeiffer syndrome , another inherited disorder that affects the skull, face, and hands.

Most commonly, JWS is associated with changes in FGFR2. Mutations in FGFR2 are also associated with the more common Crouzon syndrome , a similar inherited disease that affects the skull and face. As of 2001 it appears that the same mutations can be associated with different diseases. Some families, like the original Amish family diagnosed with Jackson-Weiss syndrome, have members who may appear to have Crouzon syndrome or Pfeiffer syndrome. The family as a whole, however, was diagnosed as having Jackson-Weiss syndrome. In 1996, two scientists proposed that the name Jackson-Weiss syndrome should strictly be used in families like the original JWS family where different family members display features of more than one of these similar disorders (Crouzon, Pfeiffer, and Apert syndromes ). As of 2001, there is controversy regarding this suggestion.


JWS has been described in different races and geographic regions. The original Jackson-Weiss family was a large Amish family with at least 138 affected members. JWS affects both sexes equally. The strongest risk factor for JWS is a family history of the disorder. As of 2001, no precise estimates on the frequency of JWS are available.

Signs and symptoms

Jackson-Weiss syndrome's hallmarks are variable skull differences, flattened mid-face, and wide big toes that angle inward toward each other. The hands are usually not involved. Rarely, deafness or mental retardation can be seen in people with JWS.

Skull abnormalities vary between individuals. Abnormalities in skull shape happen when the sutures, or open seams between the bony plates that form the skull, fuse before they normally would. Premature closure of the skull sutures is known as craniosynostosis . Growth of the brain pushes outward on skull plates that have not yet fused. In JWS different sutures may be involved leading to different head shapes. The face may be lopsided due to skull deformity.

Facial differences also vary between individuals with Jackson-Weiss syndrome. Some individuals have no obvious facial differences. The hallmark face of Jackson-Weiss syndrome has very prominent, bulging, down slanting, sometimes crossed eyes that are slightly further apart than normal with droopy eyelids. The middle third of the face is underdeveloped and somewhat flattened with a beaked nose. The forehead is rounded prominently and the hairline may be slightly lower on the forehead than usual. The chin may be small and the lower jaw may come forward more than normal. Some people with JWS may have cleft palate or a steeply arched palate (roof of the mouth). These changes may cause unusually nasal sounding speech or more serious speech difficulties.

The feet display unusually wide big toes that curve inward toward each other. The large bones of the foot may be fused or abnormally shaped. Smaller bones of the feet and toes may be abnormally shaped or absent. These bony abnormalities may be obvious only on x ray. The fingers and toes may be abnormally short with webbing of the skin between the second and third toes. Extra toes may be present at birth.


Characteristic facial features and unusual toes may be obvious to an untrained eye, but a thorough physical exam by a physician is necessary to check for less obvious differences. Bony differences may not be obvious, appearing only on x ray. Bony differences in the feet were found consistently, even in seemingly unaffected individuals, in the original Jackson-Weiss syndrome family. X ray is considered to be a very important element in diagnosing JWS. X rays are also important in determining what specific type of abnormal skull plate fusion is present.

DNA testing is available for Jackson-Weiss syndrome. This testing is performed on a blood sample in children and adults to confirm a diagnosis made on physical features. Prenatal genetic testing is also available. An unborn baby can be tested for JWS with DNA extracted from cells obtained via chorionic villus sampling or amniocentesis .

Treatment and management

There is no medication or cure for Jackson-Weiss syndrome. Treatment, if necessary, depends on an individual's symptoms. Surgery is always offered to correct the most severe physical complications, like cleft palate. Foot and facial abnormalities can also be treated with surgery if they are bothersome to an affected individual. Cosmetic surgery on the face can yield excellent results. In many cases facial differences are so mild that surgical intervention is not recommended. Counseling and support groups may be helpful to patients experiencing emotional difficulty due to physical differences.

Genetic counseling is offered to persons who have this inheritable disorder. Parents with this disease have a 50% chance of passing it to each of their children. Prenatal diagnosis for JWS is available. This prenatal genetic testing cannot, however, predict the severity or scope of an individual's symptoms. In the future, parents with genetic diseases like Jackson-Weiss syndrome may be able to opt for disease diagnosis from a cell of an embryo before the embryo is introduced to the mother's womb. This testing is called preimplantation genetic diagnosis and is already available in some centers in the United States.


The lifespan of individuals with JWS is normal. Intelligence is often normal, though borderline intelligence and mental retardation have been described in some patients with JWS.



Roscioli, T., et al. "Clinical Findings in a Patient with FGFR1 P252R Mutation and Comparison with the Literature." American Journal of Medical Genetics 93 (2000): 22-28.

Tartaglia, Marco, et al. "Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders." Human Genetics 101 (1997): 47-50.


Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. [email protected]. <http://www.ccakids.com>.

FACES. The National Craniofacial Assocation. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332-2373. [email protected]. <http://www.faces-cranio.org/>.


Online Mendelian Inheritance in Man. <http://www3.ncbi.nlm.nih.gov/Omim>.

Robin, Nathaniel, MD. [October 12, 1998]. "Craniosynostosis Syndromes (FGFR-Related)." Gene Clinics: Clinical Genetic Information Resource. University of Washington, Seattle. <http://www.geneclinics.org/profiles/craniosynostosis/index.html>

Judy C. Hawkins, MS

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Jackson-Weiss syndrome

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