Jackson-Weiss syndrome Health Article

Definition

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.

Description

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.