Langer Mesomelic Dysplasia
Langer mesomelic dysplasia is a rare skeletal disorder characterized by the severe shortening of the long bones in the arms and legs, resulting in extremely short stature.
Overview & Symptoms
Langer mesomelic dysplasia is a disorder that affects bone growth. Individuals with this condition experience extreme shortening of the long bones in their arms and legs, a clinical feature known as mesomelia. This severe shortening of the leg bones results in very short stature.
Specific skeletal abnormalities associated with the condition include:
- An underdeveloped or entirely absent ulna (a bone in the forearm) and fibula (a bone in the lower leg)
- Unusually short, thick, and curved radius bones in the forearm and tibia bones in the lower leg
- Madelung deformity, an abnormality of the wrist and forearm bones that can cause pain and limit wrist movement
- Mild underdevelopment of the lower jaw bone (mandible)
Frequency
The exact prevalence of Langer mesomelic dysplasia is unknown, but the condition is considered rare. Several dozen affected individuals have been documented in scientific literature.
Causes & Genetic Factors
Langer mesomelic dysplasia is caused by genetic changes involving the SHOX gene. The protein produced by this gene is essential for normal bone development, playing a critical role in the growth and maturation of bones in the limbs.
The most common genetic cause of the disorder is a complete deletion of the SHOX gene. Other causes include specific mutations within the SHOX gene or deletions of nearby genetic material that regulates the gene's activity. These genetic alterations severely reduce or eliminate the production of the SHOX protein. Without sufficient SHOX protein, normal bone growth is disrupted, leading to the characteristic skeletal deformities of the condition.
Inheritance Pattern
This condition is inherited in a pseudoautosomal recessive pattern. The SHOX gene is located on both the X and Y sex chromosomes in a region known as the pseudoautosomal region. Unlike genes unique to either the X or Y chromosome, genes in this region are present on both. Therefore, both females (who have two X chromosomes) and males (who have one X and one Y chromosome) normally carry two functional copies of the SHOX gene in every cell.
The inheritance is recessive because both copies of the SHOX gene must be missing or altered to cause Langer mesomelic dysplasia:
- In females, the condition occurs when the gene is altered or missing on both X chromosomes.
- In males, it occurs when the gene is altered or missing on both the X and Y chromosomes.
A related, typically less severe skeletal disorder called Léri-Weill dyschondrosteosis occurs when only one copy of the SHOX gene is mutated in each cell.
Other Names for This Condition
- Dyschondrosteosis homozygous
- Langer mesomelic dwarfism
- LMD
- Mesomelic dwarfism of the hypoplastic ulna, fibula, and mandible type