Dyschondrosteosis Health Article

Definition

Dyschondrosteosis (DCO) is a genetic form of dwarfism characterized by short forearms, short lower legs, normal-sized torso, normal-sized head, and a wrist and arm bone abnormality called Madelung deformity.

Description

Dyschondrosteosis (DCO) was first described by Leri and Weill in 1929. Leri and Weill described patients with dwarfism characterized by short lower legs, normal-sized torso, and a specific wrist and arm bone abnormality called Madelung's deformity. Other names for DCO include Leri-Weill dyschondrosteosis (LWD), Leri-Weill syndrome (LWS), Leri-Weill disease, Mesomelic dwarfism-Madelung deformity, Lamy-Bienefeld syndrome, Langer's syndrome, Langer's mesomelic dwarfism, and Langer's mesomelic dysplasia.

Genetic profile

Dyschondrosteosis (DCO) is a pseudoautosomal dominant condition caused by a change or mutation in one of two genes called SHOX and SHOY. The SHOX gene is located on the short arm of the X chromosome in the pseudoautosomal region (Xpter-p22.32). SHOY is located on the Y chromosome in the pseudoautosomal region (Ypter-p11.2). Chromosomes are the structures found in all cells that contain genes. In each cell, there are 46 chromosomes, which come in 23 pairs. One member of each pair comes from the mother, and the other from the father. The first 22 pairs are called autosomes, and are the same in males and females. The last pair of chromosomes is the sex chromosomes, X and Y. Females have two X chromosomes and males have one X chromosome and one Y chromosome. On the sex chromosomes, there are regions that contain the same genes. These regions are called the pseudoautosomal region because the genes in those regions behave as if they were on an autosomal chromosome and are the same in males and females. In 2004, it was found that 70% of families affected by DCO have a mutation in the SHOX gene. The remaining families have a mutation in the SHOY gene, or possibly another gene related to the SHOX and SHOY genes that leads to problems in bone development.

When DCO is caused by a mutated SHOX or SHOY gene, it is inherited through the family in an pseudoautosomal dominant pattern. In a pseudoautosomal dominant condition, only one nonworking copy of the gene for a particular condition is necessary for a person to experience symptoms of the condition. If a parent has a pseudoautosomal dominant condition, there is a 50% chance for each child to have the same or similar condition. DCO can also appear in an individual for the first time, and not be found in the affected individual's parents. An individual who is the first member of the family to be affected by DCO passes DCO to their children in a pseudoautosomal dominant pattern of inheritance. Accordingly, the individual who has de novo (new) DCO has the same 50% chance to have affected children.

Individuals inheriting the same nonworking gene in the same family can have very different symptoms. For example, some family members affected by DCO may be affected by proportional dwarfism with no visible arm bone deformity, while other family member may have very short (mesomelic) arms and legs and severe Made-lung deformity. The difference in physical findings within the same family is known as variable penetrance, or intrafamilial variability.

Studies in 1998 and 1999 suggested that another form of severe dwarfism, called Langer mesomelic dysplasia, is the result of inheriting two copies of the mutated gene that causes DCO. Langer mesomelic dysplasia is characterized by severe short stature with under-developed or missing arm bones.