MSX2

The MSX2 gene provides instructions for producing a protein that is necessary for proper development throughout the body. The MSX2 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 MSX2 protein seems to be particularly critical for the complete development of the skull.

enlarged parietal foramina - caused by mutations in the MSX2 gene

More than 10 mutations in the MSX2 gene have been identified in people with enlarged parietal foramina type 1. These mutations include a change of one protein building block (amino acid) in the MSX2 protein and deletions of one or more DNA building blocks (nucleotides) from the gene. These genetic changes result in the production of an unstable MSX2 protein that cannot bind to DNA. A nonfunctional MSX2 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 MSX2 gene

A mutation in the MSX2 gene causes a condition called craniosynostosis type 2 (also known as Boston type). Craniosynostosis involves a premature closure of the bones of the skull, leading to a misshapen head. People with craniosynostosis type 2 can have skull malformations including a protruding forehead (frontal bossing), a short wide head that is pointed at the top (turribrachycephaly), or a cloverleaf-shaped skull (Kleeblattschaedel deformity). Most affected people have vision problems, and a few have experienced seizures. Intelligence is typically normal.

Only one mutation has been found to cause craniosynostosis type 2. This mutation changes one protein building block (amino acid) in the MSX2 protein. Specifically, the amino acid proline is replaced with the amino acid histidine at position 148 (written Pro148His or P148H). Craniosynostosis type 2 has been found to affect multiple members of a single multi-generational family.