ALX4

The ALX4 gene provides instructions for producing a protein that is necessary for proper development throughout the body, especially in the skull and limb bones. The ALX4 protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The presence of the ALX4 protein seems to be particularly critical for the complete development of the skull.

enlarged parietal foramina - caused by mutations in the ALX4 gene

A few mutations in the ALX4 gene have been identified in people with enlarged parietal foramina type 2. These mutations include a change of one protein building block (amino acid) in the ALX4 protein and deletions of one or more DNA building blocks (nucleotides) from the gene. These genetic changes result in the production of an unstable ALX4 protein that cannot bind to DNA. A nonfunctional ALX4 protein impairs the regulation of cell growth and division (proliferation); cell maturation and specialization (differentiation); and the balance of cell survival and self-destruction in certain areas of the skull. These impairments of cell function lead to problems with bone formation (ossification), which cause enlarged parietal foramina.

other disorders - caused by mutations in the ALX4 gene

A mutation resulting in the deletion of the ALX4 gene causes a condition called proximal 11p deletion syndrome. In addition to enlarged parietal foramina, people with this condition have multiple benign bone tumors (exostoses). Signs and symptoms seen in some people with proximal 11p deletion syndrome include intellectual disability, a difference in the appearance between the right and left sides of the face (facial asymmetry), vision problems, skeletal abnormalities, and heart defects.

Proximal 11p deletion syndrome (sometimes referred to as Potocki-Shaffer syndrome) is often described as a contiguous gene deletion syndrome because it results from the loss of several genes that are close together near the center (proximal region) of chromosome 11, on the short (p) arm.

Researchers have determined that the loss of the ALX4 gene is responsible for the enlarged parietal foramina seen in people with this condition. The loss of another gene, EXT2, in the same region of chromosome 11 may help explain the multiple exostoses. Additional genes in the deleted region likely contribute to the varied features of proximal 11p deletion syndrome.