Hajdu-Cheney syndrome is a rare disorder that can affect many parts of the body, particularly the bones. Bone loss from the tips of the fingers and toes (acroosteolysis) is a characteristic feature of the condition. The fingers and toes may appear short and rounded, and they may become shorter over time as the bone continues to break down. In people with Hajdu-Cheney syndrome, the fingers are more likely to be affected than the toes. Bone loss in the fingers can interfere with fine motor skills, such as picking up small objects.

Hajdu-Cheney syndrome is associated with variants (also called mutations) in the NOTCH2 gene. This gene provides instructions for making a receptor protein. Other proteins, called ligands, can fit into specific sites on receptor proteins, like a key into a lock. When a ligand binds to the NOTCH2 receptor protein, it triggers a signaling pathway called the NOTCH2 signaling pathway. NOTCH2 signaling is important for the early development of bones and for bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. NOTCH2 signaling also appears to be involved in the development of the heart, kidneys, teeth, and other parts of the body.

Although Hajdu-Cheney syndrome is a rare disease, its exact prevalence is unknown. Fewer than 100 affected individuals have been described in the medical literature.

Hajdu-Cheney syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Many cases of this condition result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Published Date: December 15, 2025
Published By: National Institutes of Health