Which are the causes of Kniest Dysplasia?

Kniest Dysplasia is a rare genetic disorder that affects the development of bones and connective tissues. It is classified as a type II collagenopathy, as it is caused by mutations in the COL2A1 gene, which provides instructions for making type II collagen. Type II collagen is a protein that is essential for the normal development of bones and other connective tissues.

Genetic Mutations: The primary cause of Kniest Dysplasia is mutations in the COL2A1 gene. These mutations can be inherited from one or both parents or can occur spontaneously during the formation of reproductive cells or early embryonic development. The mutations disrupt the production or structure of type II collagen, leading to abnormal bone and connective tissue development.

Autosomal Dominant Inheritance: In most cases, Kniest Dysplasia follows an autosomal dominant pattern of inheritance. This means that a person with a mutation in one copy of the COL2A1 gene has a 50% chance of passing on the condition to each of their children. However, some cases may occur sporadically without a family history of the disorder.

De Novo Mutations: Sporadic cases of Kniest Dysplasia can occur due to de novo mutations. These mutations arise in the egg, sperm, or early embryo and are not inherited from either parent. The exact cause of de novo mutations is not well understood, but they are thought to occur randomly and are not influenced by environmental factors.

Impact on Collagen Production: The mutations in the COL2A1 gene disrupt the production of type II collagen or alter its structure. Type II collagen is a crucial component of cartilage, which is responsible for the growth and development of bones. The abnormal collagen production leads to skeletal abnormalities, including short stature, abnormal curvature of the spine (scoliosis), and joint problems.

Other Factors: While the primary cause of Kniest Dysplasia is genetic mutations, other factors can influence the severity and presentation of the disorder. These factors include variations in the specific mutation, genetic modifiers, and environmental factors. However, further research is needed to fully understand the interplay between these factors and the development of Kniest Dysplasia.