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MSX2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MSX2 gene

The MSX2 gene provides instructions for producing a protein that acts as a transcription factor, playing a critical role in the development of cells and tissues, particularly the skull.

Normal Function

The MSX2 gene provides instructions for producing a protein that is necessary for proper development of cells and tissues 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. Specifically, the protein controls the activity of genes that regulate cell growth and division (proliferation), cell maturation and specialization (differentiation), and cell survival. The regulation of these functions ensures that cells start and stop growing at specific times and that they are positioned correctly during development.

The MSX2 protein is part of a chemical signaling pathway known as the bone morphogenic protein (BMP) pathway. This signaling pathway regulates various cellular processes and is involved in the growth of cells, including new bone cells. The MSX2 protein seems to be particularly critical for the development of the skull.

Health Conditions Related to Genetic Changes

Enlarged parietal foramina

At least 10 mutations in the MSX2 gene have been identified in people with enlarged parietal foramina type 1. This condition is characterized by enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. Openings in the parietal bones are normal during fetal development, but they usually close before birth. In people with this condition, the parietal foramina remain open throughout life.

The mutations that cause enlarged parietal foramina result in the production of an MSX2 protein that cannot bind to DNA, which alters the regulation of multiple genes. As a result, several cell processes are disrupted, including proliferation, differentiation, and survival. In early development, the skull seems to be particularly sensitive to changes in MSX2 protein activity and changes in cell function. Specifically, cells in the skull that are involved in bone formation (ossification) cannot function normally, leading to a lack of bone in areas of the skull and enlarged parietal foramina.

Other disorders

At least two mutations in the MSX2 gene cause a condition called craniosynostosis type 2 (also known as Boston type craniosynostosis). Craniosynostosis involves 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.

It is unclear how changes in the MSX2 gene can cause premature closure of the skull bones in craniosynostosis type 2 and impaired bone formation in enlarged parietal foramina.

Other Names for This Gene

  • CRS2
  • FPP
  • HOX8
  • MSH
  • msh homeobox homolog 2
  • MSX2_HUMAN
  • PFM
  • PFM1

Frequently Asked Questions

Because the parietal bone openings leave underlying brain tissue and dural sinuses partially unprotected by bone, the primary management involves preventing direct cranial trauma. Children are usually advised to wear custom protective helmets during high-impact physical play, bicycle riding, or sports, and to strictly avoid collision or contact sports. Parents should also monitor the soft depressions as the child grows.
Yes. While frequently an isolated skeletal finding, enlarged parietal foramina can be accompanied by persistent fetal dural venous anatomy, such as aberrant straight sinuses or accessory occipital sinuses, as well as scalp defects like aplasia cutis congenita. Neuroimaging with MR or CT venography is often recommended before any surgical or cranial intervention to rule out associated vascular malformations.
No, the defects do not close entirely. While parietal foramina are normal developmental gaps in fetal life that typically ossify before birth, loss-of-function MSX2 mutations permanently stall intramembranous bone formation. The openings often narrow slightly as the surrounding skull matures during early childhood, but they persist as permanent bilateral symmetrical cranial defects throughout adulthood.
The clinical outcome depends on whether the mutation reduces or increases MSX2 protein activity. Loss-of-function mutations or deletions cause enlarged parietal foramina type 1 due to insufficient bone growth signaling. In contrast, specific gain-of-function missense mutations (such as Pro148His) overactivate downstream bone morphogenetic protein pathways, causing premature cranial suture fusion known as Boston-type craniosynostosis.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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