Which are the causes of Wiedemann-Steiner Syndrome?

Wiedemann-Steiner Syndrome (WSS) is a rare genetic disorder characterized by a variety of physical and developmental features. It was first described in 1989 by Wiedemann and Steiner, hence the name. WSS is caused by mutations in the KMT2A gene, also known as the MLL gene.

The KMT2A gene provides instructions for making a protein that plays a crucial role in regulating gene expression. Gene expression is the process by which information from a gene is used to create a functional product, such as a protein. The protein produced by the KMT2A gene is involved in the modification of histones, which are proteins that help package DNA in the nucleus of cells. These modifications help control the activation or repression of specific genes.

Most cases of WSS are caused by de novo mutations, which means they occur spontaneously and are not inherited from parents. These mutations can occur during the formation of reproductive cells (eggs or sperm) or early in embryonic development. The exact mechanisms by which these mutations lead to the development of WSS are not fully understood.

WSS is considered an autosomal dominant disorder, which means that a mutation in only one copy of the KMT2A gene is sufficient to cause the condition. However, some individuals with WSS have been found to have mutations in both copies of the gene, suggesting that the disorder may have a more complex inheritance pattern.

The specific mutations in the KMT2A gene associated with WSS can vary among affected individuals. These mutations can lead to a loss of function or altered function of the protein produced by the gene. As a result, there is a disruption in the normal regulation of gene expression, which can have widespread effects on development and function of various organs and systems in the body.

Individuals with WSS typically exhibit a range of physical and developmental features. These may include distinctive facial features such as a broad nasal bridge, thick eyebrows, long eyelashes, and a wide mouth. They may also have short stature, intellectual disability, and developmental delays. Other common features include hypotonia (low muscle tone), feeding difficulties, seizures, and behavioral problems.

In conclusion, Wiedemann-Steiner Syndrome is caused by mutations in the KMT2A gene, which disrupts the normal regulation of gene expression. The exact mechanisms by which these mutations lead to the development of WSS are still being investigated. The disorder is typically characterized by a variety of physical and developmental features, including distinctive facial features, short stature, intellectual disability, and developmental delays.