Which are the causes of Weaver Syndrome?

Weaver syndrome is a rare genetic disorder characterized by rapid growth and development abnormalities. It was first described in 1974 by Dr. David Weaver, hence the name. This condition affects both males and females, and its exact prevalence is unknown. The causes of Weaver syndrome are primarily genetic, resulting from mutations in specific genes.

Genetic mutations: Weaver syndrome is primarily caused by mutations in the EZH2 gene, which provides instructions for making a protein involved in gene regulation. These mutations are usually spontaneous, meaning they occur randomly and are not inherited from parents. The specific mutations in the EZH2 gene lead to the overgrowth and developmental abnormalities observed in individuals with Weaver syndrome.

Epigenetic changes: EZH2 is part of a group of proteins called polycomb repressive complex 2 (PRC2), which plays a crucial role in regulating gene expression. Mutations in the EZH2 gene disrupt the normal function of PRC2, leading to epigenetic changes. Epigenetic modifications are alterations in gene activity that do not involve changes to the DNA sequence itself. These changes can affect how genes are turned on or off, leading to the characteristic features of Weaver syndrome.

Parental mosaicism: In some cases, Weaver syndrome can be inherited from a parent who has a mosaic mutation in their germ cells. Mosaicism refers to the presence of different genetic makeup in different cells of an individual's body. If a parent has a mosaic mutation in their germ cells (sperm or eggs), they can pass on the mutation to their child, resulting in Weaver syndrome.

Other genetic factors: While mutations in the EZH2 gene are the primary cause of Weaver syndrome, there may be other genetic factors involved. Researchers are still investigating the potential contribution of additional genes or genetic variations that could modify the severity or presentation of the syndrome.

Environmental factors: It is important to note that Weaver syndrome is primarily a genetic disorder, and there is no evidence to suggest that environmental factors play a significant role in its development.

In conclusion, Weaver syndrome is primarily caused by mutations in the EZH2 gene, leading to disruptions in gene regulation and epigenetic changes. These mutations are usually spontaneous, but in some cases, the syndrome can be inherited from a parent with a mosaic mutation. Understanding the underlying genetic causes of Weaver syndrome is crucial for diagnosis, management, and potential future treatments.