Leri-Weill dyschondrosteosis

Definition

Leri-Weill dyschondrosteosis (LWD) is a rare form of dwarfism. It is characterized by short forearms and lower legs as well as a certain arm-bone abnormality (Madelung deformity).

Description

LWD was first described by A. Leri and J. Weill in 1929. Other names for LWD include Leri-Weill syndrome (LWS), dyschondrosteosis (DCO), and Madelung deformity.

Genetic profile

LWD appears to be caused by several genetic factors. Many forms of LWD are caused by a mutation (change) in a gene called SHOX (for "short stature homeo box" gene). SHOX is located on the X chromosome. In the cases of LWD in which a specific mutation or change cannot be found in the SHOX gene, another gene may be responsible for the problems in bone development. The involvement of another gene or some other factor would not be surprising, as a person's height is determined by the interaction of many genes and environmental factors.

Leri-Weill dyschondrosteosis can appear in an individual but not be found in his or her parents. A new, isolated type of LWD is called denovo LWD. A person with denovo LWD has a 50% chance of having children with the syndrome.

Family members with the syndrome can be affected very differently. For example, some family members may have proportional dwarfism, with no visible arm-bone abnormality, while other family members may have very short (mesomelic) arms and legs and severe Madelung arm-bone abnormality. Such differences in physical findings within the same family are known as intrafamilial variability.

Studies in 1998 and 1999 suggested that another form of severe dwarfism, Langer mesomelic dysplasia , is the result of inheriting two copies of the mutated gene that causes LWD. Langer mesomelic dysplasia is characterized by extremely short stature along with underdeveloped or missing arm bones.

Demographics

The ethnic origins of individuals affected by LWD are varied. LWD does not appear to be more common in any specific country.

Signs and symptoms

Most individuals affected by Leri-Weill dyschrondrosteosis have short stature based on their shortened lower legs and forearms, normal head size, and Madelung deformity. One recent study found that some males have overdeveloped muscles (or muscular hypertrophy). Depending on the individual, LWD can result in severe to very mild symptoms (variable expression). Females affected by LWD tend to have the more severe effects of LWD.

Some individuals with LWD have symptoms not part of the LWD features. These features, such as mental retardation and skin disorders, are believed to be caused by abnormalities in genes close to the mutated SHOX gene. Individuals with other symptoms as well as LWD are said to be affected by an Xp22.3 contiguous gene syndrome. The name refers to a syndrome caused by the deletion or incorrect working of several genes found side-by-side on the X chromosome.

Diagnosis

Diagnosis of LWD is usually made from physical examination by a medical geneticist, and by studies of x rays of the legs and arms. Madelung deformity of the arms is generally not visible in children through physical exam, but the first signs of the abnormality, such as bowing of the forearm bone, can be identified by x ray between ages two and five years.

Although one gene has been found to cause LWD, diagnostic genetic testing in affected individuals or in fetuses is not available in 2001.

Treatment and management

At this time there is no specific therapy that removes, cures, or repairs all signs of the disorder. Some progress in increasing height has been made by growth hormone (GH) supplementation in affected children. However, this treatment causes disproportionate growth, with longer arms and trunk and shorter legs.

Prognosis

The severity of effects of LWD varies widely, so prognoses for people with the syndrome also vary. Severe Madelung deformity may require surgery. However, individuals with LWD have an excellent prognosis, and most have normal lives.

Resources

BOOKS

Charles, I., et al. Dwarfism: The Family and ProfessionalGuide. Short Stature Foundation Press, 1994.

Rieser, Patricia, and Heino F. L. Mayer-Bahlburg. Short &Okay: A Guide for Parents of Short Children. Human Growth Foundation.

ORGANIZATIONS

Human Growth Foundation. 997 Glen Cove Ave., Glen Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055. <http://www.hgf1@hgfound.org>.

International Center for Skeletal Dysplasia. Saint Joseph's Hospital, 7620 York Rd., Towson, MD 21204. (410) 337-1250.

Little People of America, Inc. National Headquarters, PO Box 745, Lubbock, TX 79408. (806) 737-8186 or (888) LPA-2001. lpadatabase@juno.com. <http://www.lpaonline.org>.

MAGIC Foundation for Children's Growth. 1327 N. Harlem Ave., Oak Park, IL 60302. (708) 383-0808 or (800) 362-4423. Fax: (708) 383-0899. mary@magicfoundation.org. <http://www.magicfoundation.org/ghd.html>.

WEBSITES

"Entry 312865: Short Stature Homeo Box; SHOX." OMIM—Online Mendelian Inheritance of Man.<http://www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=312865>.

Family Village.<http://www.familyvillage.wisc.edu/index.html>

Dawn A. Jacob, MS